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Rheumatoid Arthritis: HELP
Articles by Ted R. Mikuls
Based on 120 articles published since 2009
(Why 120 articles?)
||||

Between 2009 and 2019, T. Mikuls wrote the following 120 articles about Arthritis, Rheumatoid.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Guideline 2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty. 2017

Goodman, Susan M / Springer, Bryan / Guyatt, Gordon / Abdel, Matthew P / Dasa, Vinod / George, Michael / Gewurz-Singer, Ora / Giles, Jon T / Johnson, Beverly / Lee, Steve / Mandl, Lisa A / Mont, Michael A / Sculco, Peter / Sporer, Scott / Stryker, Louis / Turgunbaev, Marat / Brause, Barry / Chen, Antonia F / Gililland, Jeremy / Goodman, Mark / Hurley-Rosenblatt, Arlene / Kirou, Kyriakos / Losina, Elena / MacKenzie, Ronald / Michaud, Kaleb / Mikuls, Ted / Russell, Linda / Sah, Alexander / Miller, Amy S / Singh, Jasvinder A / Yates, Adolph. ·Susan M. Goodman, MD, Lisa A. Mandl, MD, MPH, Peter Sculco, MD, Barry Brause, MD, Kyriakos Kirou, MD, Ronald MacKenzie, MD, Linda Russell, MD: Hospital for Special Surgery/Weill Cornell Medicine, New York, New York. Electronic address: goodmans@hss.edu. · Bryan Springer, MD: OrthoCarolina Hip and Knee Center, Charlotte, North Carolina. · Gordon Guyatt, MD: McMaster University, Hamilton, Ontario, Canada. · Matthew P. Abdel, MD: Mayo Clinic, Rochester, Minnesota. · Vinod Dasa, MD: Louisiana State University, New Orleans. · Michael George, MD: University of Pennsylvania, Philadelphia. · Ora Gewurz-Singer, MD: University of Michigan, Ann Arbor. · Jon T. Giles, MD, MPH: Columbia University, New York, New York. · Beverly Johnson, MD: Albert Einstein College of Medicine, Bronx, New York. · Steve Lee, DO: Kaiser Permanente, Fontana, California. · Susan M. Goodman, MD, Lisa A. Mandl, MD, MPH, Peter Sculco, MD, Barry Brause, MD, Kyriakos Kirou, MD, Ronald MacKenzie, MD, Linda Russell, MD: Hospital for Special Surgery/Weill Cornell Medicine, New York, New York. · Michael A. Mont, MD: Cleveland Clinic, Cleveland, Ohio. · Scott Sporer, MD: Midwest Orthopaedics at Rush, Chicago, Illinois. · Louis Stryker, MD: University of Texas Medical Branch, Galveston. · Marat Turgunbaev, MD, MPH, Amy S. Miller: American College of Rheumatology, Atlanta, Georgia. · Antonia F. Chen, MD, MBA: Rothman Institute, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. · Jeremy Gililland, MD: University of Utah, Salt Lake City. · Mark Goodman, MD, Adolph Yates, MD: University of Pittsburgh, Pittsburgh, Pennsylvania. · Arlene Hurley-Rosenblatt, ANP: Rockefeller University, New York, New York. · Elena Losina, PhD: Brigham and Women's Hospital, Boston, Massachusetts. · Kaleb Michaud, PhD: National Data Bank for Rheumatic Diseases, Wichita, Kansas and University of Nebraska Medical Center, Omaha. · Ted Mikuls, MD, MSPH: University of Nebraska Medical Center, Omaha. · Alexander Sah, MD: Dearborn-Sah Institute for Joint Restoration, Fremont, California. · Jasvinder A. Singh, MBBS, MPH: University of Alabama at Birmingham. ·J Arthroplasty · Pubmed #28629905.

ABSTRACT: OBJECTIVE: This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). METHODS: A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi-step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. RESULTS: The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease-modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional and based on low- or moderate-quality evidence. CONCLUSION: This guideline should help decision-making by clinicians and patients regarding perioperative antirheumatic medication management at the time of elective THA or TKA. These conditional recommendations reflect the paucity of high-quality direct randomized controlled trial data.

2 Guideline 2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty. 2017

Goodman, Susan M / Springer, Bryan / Guyatt, Gordon / Abdel, Matthew P / Dasa, Vinod / George, Michael / Gewurz-Singer, Ora / Giles, Jon T / Johnson, Beverly / Lee, Steve / Mandl, Lisa A / Mont, Michael A / Sculco, Peter / Sporer, Scott / Stryker, Louis / Turgunbaev, Marat / Brause, Barry / Chen, Antonia F / Gililland, Jeremy / Goodman, Mark / Hurley-Rosenblatt, Arlene / Kirou, Kyriakos / Losina, Elena / MacKenzie, Ronald / Michaud, Kaleb / Mikuls, Ted / Russell, Linda / Sah, Alexander / Miller, Amy S / Singh, Jasvinder A / Yates, Adolph. ·Hospital for Special Surgery/Weill Cornell Medicine, New York, New York. · OrthoCarolina Hip and Knee Center, Charlotte, North Carolina. · McMaster University, Hamilton, Ontario, Canada. · Mayo Clinic, Rochester, Minnesota. · Louisiana State University, New Orleans. · University of Pennsylvania, Philadelphia. · University of Michigan, Ann Arbor. · Columbia University, New York, New York. · Albert Einstein College of Medicine, Bronx, New York. · Kaiser Permanente, Fontana, California. · Cleveland Clinic, Cleveland, Ohio. · Midwest Orthopaedics at Rush, Chicago, Illinois. · University of Texas Medical Branch, Galveston. · American College of Rheumatology, Atlanta, Georgia. · Rothman Institute, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. · University of Utah, Salt Lake City. · University of Pittsburgh, Pittsburgh, Pennsylvania. · Rockefeller University, New York, New York. · Brigham and Women's Hospital, Boston, Massachusetts. · National Data Bank for Rheumatic Diseases, Wichita, Kansas, and University of Nebraska Medical Center, Omaha. · University of Nebraska Medical Center, Omaha. · Dearborn-Sah Institute for Joint Restoration, Fremont, California. · University of Alabama at Birmingham. ·Arthritis Rheumatol · Pubmed #28620948.

ABSTRACT: OBJECTIVE: This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). METHODS: A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi-step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. RESULTS: The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease-modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional and based on low- or moderate-quality evidence. CONCLUSION: This guideline should help decision-making by clinicians and patients regarding perioperative antirheumatic medication management at the time of elective THA or TKA. These conditional recommendations reflect the paucity of high-quality direct randomized controlled trial data.

3 Editorial To improve outcomes we must define and measure them: toward defining remission in rheumatoid arthritis. 2011

O'Dell, James R / Mikuls, Ted R. · ·Arthritis Rheum · Pubmed #21294107.

ABSTRACT: -- No abstract --

4 Editorial Help stop tooth decay...and prevent RA? 2010

Mikuls, Ted R. · ·J Rheumatol · Pubmed #20516033.

ABSTRACT: -- No abstract --

5 Editorial Rheumatoid arthritis incidence: what goes down must go up? 2010

Mikuls, Ted R. · ·Arthritis Rheum · Pubmed #20191577.

ABSTRACT: -- No abstract --

6 Editorial Physician preference: filling the evidence gap. 2010

Mikuls, Ted R / O'Dell, James R. · ·Arthritis Care Res (Hoboken) · Pubmed #20191484.

ABSTRACT: -- No abstract --

7 Review Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications. 2018

England, Bryant R / Thiele, Geoffrey M / Anderson, Daniel R / Mikuls, Ted R. ·Veterans Affairs (VA) Nebraska-Western Iowa Health Care System, Omaha, NE, USA. · Division of Rheumatology and Immunology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA. · Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA. · Veterans Affairs (VA) Nebraska-Western Iowa Health Care System, Omaha, NE, USA tmikuls@unmc.edu. ·BMJ · Pubmed #29685876.

ABSTRACT: Rheumatoid arthritis is a systemic autoimmune disease characterized by excess morbidity and mortality from cardiovascular disease. Mechanisms linking rheumatoid arthritis and cardiovascular disease include shared inflammatory mediators, post-translational modifications of peptides/proteins and subsequent immune responses, alterations in the composition and function of lipoproteins, increased oxidative stress, and endothelial dysfunction. Despite a growing understanding of these mechanisms and their complex interplay with conventional cardiovascular risk factors, optimal approaches of risk stratification, prevention, and treatment in the context of rheumatoid arthritis remain unknown. A multifaceted approach to reduce the burden posed by cardiovascular disease requires optimal management of traditional risk factors in addition to those intrinsic to rheumatoid arthritis such as increased disease activity. Treatments for rheumatoid arthritis seem to exert differential effects on cardiovascular risk as well as the mechanisms linking these conditions. More research is needed to establish whether preferential rheumatoid arthritis therapies exist in terms of prevention of cardiovascular disease. Ultimately, understanding the unique mechanisms for cardiovascular disease in rheumatoid arthritis will aid in risk stratification and the identification of novel targets for meaningful reduction of cardiovascular risk in this patient population.

8 Review Recent advances in the treatment of rheumatoid arthritis. 2018

Mahajan, Tina D / Mikuls, Ted R. ·Division of Rheumatology, Department of Internal Medicine. · Veterans Affairs Nebraska-Western Iowa Healthcare System, University of Nebraska Medical Center, Omaha, NE, USA. ·Curr Opin Rheumatol · Pubmed #29461286.

ABSTRACT: PURPOSE OF REVIEW: Therapies for rheumatoid arthritis (RA) continue to expand rapidly. The purpose of this review is to discuss novel treatment options, including biosimilars, that are available, as well as to highlight promising agents in development. The purpose is also to discuss new emerging safety signals associated with these drugs and to discuss strategies in tapering therapy. RECENT FINDINGS: There are several novel RA therapies. These include the interleukin-6 (IL-6) receptor blocker sarilumab, which was approved in 2017. In aggregate, the sarilumab studies show that it is effective in RA, including patients with incomplete responses to methotrexate and anti-tumor necrosis factor inhibitor, and showing superior efficacy when used in higher dose (200 mg every 2 weeks) to standard-dose adalilumab. Other drugs that are currently being studied include the IL-6 cytokine blocker sarikumab, the small targeted molecule filgotinib, and many new biosimilars. Baracitinib failed to achieve approval by the Food and Drug Administration primarily over perceived safety concerns. The two biosimilar drugs currently approved are CT-P13 and SB2, which are based on the reference product infliximab. Although this review summarizes trials examining biologic tapering, additional data are needed to guide clinicians in regards to treatment de-escalation in RA. SUMMARY: With the greatly expanded armamentarium of RA treatment options available, it is important for clinicians to understand the data regarding drug efficacy and safety. With remission increasingly attainable, effective drug tapering strategies are needed. Although tapering trials do exist, more studies will be needed to help guide clinical practice.

9 Review 2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty. 2017

Goodman, Susan M / Springer, Bryan / Guyatt, Gordon / Abdel, Matthew P / Dasa, Vinod / George, Michael / Gewurz-Singer, Ora / Giles, Jon T / Johnson, Beverly / Lee, Steve / Mandl, Lisa A / Mont, Michael A / Sculco, Peter / Sporer, Scott / Stryker, Louis / Turgunbaev, Marat / Brause, Barry / Chen, Antonia F / Gililland, Jeremy / Goodman, Mark / Hurley-Rosenblatt, Arlene / Kirou, Kyriakos / Losina, Elena / MacKenzie, Ronald / Michaud, Kaleb / Mikuls, Ted / Russell, Linda / Sah, Alexander / Miller, Amy S / Singh, Jasvinder A / Yates, Adolph. ·Hospital for Special Surgery/Weill Cornell Medicine, New York, New York. · OrthoCarolina Hip and Knee Center, Charlotte, North Carolina. · McMaster University, Hamilton, Ontario, Canada. · Mayo Clinic, Rochester, Minnesota. · Louisiana State University, New Orleans. · University of Pennsylvania, Philadelphia. · University of Michigan, Ann Arbor. · Columbia University, New York, New York. · Albert Einstein College of Medicine, Bronx, New York. · Kaiser Permanente, Fontana, California. · Cleveland Clinic, Cleveland, Ohio. · Midwest Orthopaedics at Rush, Chicago, Illinois. · University of Texas Medical Branch, Galveston. · American College of Rheumatology, Atlanta, Georgia. · Rothman Institute, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. · University of Utah, Salt Lake City. · University of Pittsburgh, Pittsburgh, Pennsylvania. · Rockefeller University, New York, New York. · Brigham and Women's Hospital, Boston, Massachusetts. · National Data Bank for Rheumatic Diseases, Wichita, Kansas and University of Nebraska Medical Center, Omaha. · University of Nebraska Medical Center, Omaha. · Dearborn-Sah Institute for Joint Restoration, Fremont, California. · University of Alabama at Birmingham. ·Arthritis Care Res (Hoboken) · Pubmed #28620917.

ABSTRACT: OBJECTIVE: This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). METHODS: A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi-step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. RESULTS: The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease-modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional and based on low- or moderate-quality evidence. CONCLUSION: This guideline should help decision-making by clinicians and patients regarding perioperative antirheumatic medication management at the time of elective THA or TKA. These conditional recommendations reflect the paucity of high-quality direct randomized controlled trial data.

10 Review Anticitrullinated protein antibodies: origin and role in the pathogenesis of rheumatoid arthritis. 2017

England, Bryant R / Thiele, Geoffrey M / Mikuls, Ted R. ·Veterans Affairs Nebraska-Western Iowa Healthcare System and Division of Rheumatology and Immunology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA. ·Curr Opin Rheumatol · Pubmed #27755123.

ABSTRACT: PURPOSE OF REVIEW: This article reviews recent literature on the origin and pathogenic role of anticitrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA). RECENT FINDINGS: ACPAs and ACPA-immune complexes interact with immune cells to facilitate articular inflammation. Findings from recent in vitro and in vivo studies are congruent with epidemiologic observations in RA supporting a pathogenic role of ACPAs. SUMMARY: ACPAs target proteins/peptides with citrullinated epitopes and serve as informative RA biomarkers. ACPAs are generated within synovium and possibly at extra-articular sites prior to disease onset. Proximate to RA onset, critical qualitative and quantitative changes to ACPAs occur that drive proinflammatory responses. Unable to induce arthritis alone, the administration of ACPAs enhances the development and severity of inflammation in mice when a mild synovitis is already present. In vitro studies have elucidated several possible mechanisms linking ACPA to disease progression including: first, activation of inflammatory cells by ACPA-immune complexes; second, ACPA-mediated neutrophil cell death producing neutrophil extracellular traps, which drives inflammation and autoimmunity by releasing citrullinated autoantigen; and finally, direct binding of ACPAs to osteoclasts and resulting osteoclastogenesis. Together, these recent investigations have begun to elucidate the different mechanisms by which ACPAs may be directly pathogenic in RA.

11 Review Autoimmunity of the lung and oral mucosa in a multisystem inflammatory disease: The spark that lights the fire in rheumatoid arthritis? 2016

Mikuls, Ted R / Payne, Jeffrey B / Deane, Kevin D / Thiele, Geoffrey M. ·Division of Rheumatology, Department of Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, Neb; Veterans Affairs (VA) Nebraska-Western Iowa Health Care System, Omaha, Neb. Electronic address: tmikuls@unmc.edu. · Division of Rheumatology, Department of Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, Neb; Division of Periodontics, Department of Surgical Specialties, College of Dentistry, University of Nebraska Medical Center, Lincoln, Neb. · Division of Rheumatology, Department of Medicine, University of Colorado, Aurora, Colo. · Division of Rheumatology, Department of Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, Neb; Veterans Affairs (VA) Nebraska-Western Iowa Health Care System, Omaha, Neb. ·J Allergy Clin Immunol · Pubmed #26768760.

ABSTRACT: There is a growing body of evidence to suggest that autoimmunity in patients with rheumatoid arthritis (RA) is initiated outside the joint. This is supported by the observation that circulating autoantibodies, including both rheumatoid factor and anti-citrullinated protein antibody, can be detected in many subjects years before the development of initial joint symptoms leading to an RA diagnosis. Of the potential extra-articular sites implicated in disease initiation, mucosal tissues have garnered increasing attention. Several lines of investigation have separately implicated mucosal tissues from varying anatomic locations as possible initiating sites for RA, including those from the lung and oral cavity. In this review we summarize recent reports incriminating these mucosal tissues as the initial site of autoantibody generation and inflammation in patients with RA.

12 Review Cardiovascular risk and the use of biologic agents in rheumatoid arthritis. 2014

Lim, Debbie T / Cannella, Amy C / Michaud, Kaleb D / Mikuls, Ted R. ·Division of Rheumatology, University of Nebraska Medical Center, 983025 Nebraska Medical Center, Omaha, NE, 68198-3025, USA, dev.lim@unmc.edu. ·Curr Rheumatol Rep · Pubmed #25315196.

ABSTRACT: Although patients with rheumatoid arthritis (RA) are recognized to be disproportionately impacted by cardiovascular disease (CVD), effective approaches of primary and secondary CVD prevention have not been well defined in this population. Given their robust disease-modifying potential and effects on both pro-inflammatory and pro-atherogenic pathways, there has been substantial speculation that biologic treatments may serve as a means of providing highly effective RA disease control while simultaneously reducing CVD risk in this high risk group. In this review, we examine available evidence relevant to the associations of approved biologic treatments with CVD outcomes in the context of RA.

13 Review Impact of total shoulder arthroplasty on generic and shoulder-specific health-related quality-of-life measures: a systematic literature review and meta-analysis. 2012

Carter, Michael J / Mikuls, Ted R / Nayak, Smita / Fehringer, Edward V / Michaud, Kaleb. ·University of Nebraska Medical Center, 986270 Nebraska Medical Center, Omaha, NE 68198-6270, USA. kmichaud@unmc.edu ·J Bone Joint Surg Am · Pubmed #22992856.

ABSTRACT: BACKGROUND: Total shoulder arthroplasty is increasingly used in the treatment of arthritis. However, the effect of total shoulder arthroplasty on health-related quality of life has not been fully established. The goal of this systematic review and meta-analysis was to characterize the change in generic and shoulder-specific health-related quality-of-life measures resulting from total shoulder arthroplasty. METHODS: We identified published studies reporting preoperative and postoperative health-related quality-of-life outcomes for patients receiving total shoulder arthroplasty. Health-related quality-of-life measures were identified, and meta-analysis was used to calculate standardized mean differences (SMDs, reflective of the effect size) and 95% confidence intervals for each scale. RESULTS: Twenty studies (1576 total shoulder replacements) met the inclusion criteria. Outcome measures were analyzed after an average postoperative follow-up duration of 3.7 ± 2.2 years. The Short Form-36 demonstrated significant improvement in physical component summary scores (SMD = 0.7, p < 0.001) but not in mental component summary scores (SMD = 0.2, p = 0.37). Significant improvements were observed in the visual analog scale score for pain (SMD = -2.5, p < 0.001) and scores on three shoulder-specific measures: the Constant score (SMD = 2.7, p < 0.001), American Shoulder and Elbow Surgeons score (SMD = 2.9, p < 0.001), and Simple Shoulder Test (SMD = 2.3, p < 0.001). CONCLUSIONS: Total shoulder arthroplasty leads to significant improvements in scores for function and pain. Shoulder-specific measures of function consistently showed the greatest degree of improvement, with large effect sizes. Total shoulder arthroplasty also leads to significant improvements in overall physical well-being, with a moderate-to-large effect size.

14 Review Environmental exposures and rheumatoid arthritis risk. 2011

Hoovestol, Ryan A / Mikuls, Ted R. ·Department of Medicine, 982055 Nebraska Medical Center, Omaha, NE 68198-2055, USA. rhoovest@unmc.edu ·Curr Rheumatol Rep · Pubmed #21785978.

ABSTRACT: In addition to rapidly burgeoning data regarding novel genetic risk factors, a growing list of environmental exposures have been implicated in rheumatoid arthritis (RA) susceptibility. Cigarette smoking is chief among the many environmental exposures implicated in disease risk, accounting for approximately one in six new cases of RA, with recent results underscoring the central importance of select gene-smoking interactions in RA development. In this review, we examine data linking several environmental exposures with RA risk, including cigarette smoking, other air pollutants and occupational exposures, reproductive/hormonal influences, alcohol consumption, select infections leading to periodontal disease, and dietary factors. Where applicable, we review the current understanding of biologic mechanisms linking these environmental factors to disease risk.

15 Article Evaluation of cytokine profiles in rheumatoid arthritis patients with clinically active disease and normal inflammatory indices. 2019

Alex, Asha M / Sayles, Harlan / Mikuls, Ted R / Kerr, Gail S. ·Medstar Georgetown University Hospital, Washington, DC, USA. · Washington DC Veteran Affairs Medical Center, Washington, DC, USA. · University of Nebraska Medical Center & VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA. · Medstar Georgetown University Hospital, Washington, DC, USA. gail.kerr@va.gov. · Washington DC Veteran Affairs Medical Center, Washington, DC, USA. gail.kerr@va.gov. · Howard University, Washington, DC, USA. gail.kerr@va.gov. · Rheumatology Section, 151K, Veterans Affairs Medical Center, 50 Irving St, NW, Washington, DC, 20422, USA. gail.kerr@va.gov. ·Clin Rheumatol · Pubmed #30506404.

ABSTRACT: OBJECTIVE: To assess the potential utility of a cytokine measurement in rheumatoid arthritis (RA) patients with active joint disease but normal acute phase reactants (APR). METHODS: RA patients in a longitudinal observational registry with available cytokine array data were included. Patients were categorized based on agreement/disagreement of physical examination and APR measurements: concordant high (CH) [high tender and/or swollen joint counts (TJC + SJC > 3) and APR (ESR ≥ 28 mm/h + CRP ≥ 1.5 mg/L)]; concordant low (CL) [TJC + SJC ≤ 3 and normal APR]. Discordant (D) [TJC + SJC > 3 and normal APR] patients were stratified into low, medium, and high-disease activity (DL, DM, DH). Weighted-average and log-transformed cytokine scores were calculated based on results of a cytokine array. Chi-square tests compared categorical variables by concordance status; t tests, Wilcoxon rank-sum tests, ANOVA models, and ordinary least squares (OLS) regressions were used to compare continuous measures. RESULTS: RA patients (n = 1467) were predominantly male (91%). Compared to CH patients (n = 174), D (n = 434) were younger, less frequently seropositive, with lower TJC, SJC, and DAS28-3v scores (p < 0.001). Cytokine scores for DL, DM, and DH groups were lower than CH patients (p < 0.001) and did not differ between DL, DM, and DH subgroups and were similar to CL (n = 356) patients. In multivariable analyses including CH and D patients, log-cytokine score was associated with higher DAS28-3v scores (p = 0.029). In multivariable analyses including CL patients, concordance status (p = 0.011) and ACPA (p = 0.013) were predictors of higher log cytokine score. CONCLUSION: In this study, cytokine scores did not identify active joint disease in RA patients with normal APR.

16 Article Body mass index and persistence of conventional DMARDs and TNF inhibitors in rheumatoid arthritis. 2019

McCulley, Caroline B / Barton, Jennifer L / Cannon, Grant W / Sauer, Brian C / Teng, Chia Chen / George, Michael D / Caplan, Liron / England, Bryant R / Mikuls, Ted R / Baker, Joshua F. ·VA Portland Health Care System; Oregon Health & Science University, OR, USA. caroline.bonafede@gmail.com. · VA Portland Health Care System; Oregon Health & Science University, OR, USA. · VA Salt Lake City Healthcare System; University of Utah; Salt Lake City VA Medical Center (IDEAS 2.0) University of Utah, Division of Epidemiology, Team VERITAS, OR, USA. · Division of Rheumatology, University of Pennsylvania, Philadelphia, PA, USA. · Department of Medicine, Rocky Mountain VA Medical Center, Aurora, CO, USA. · VA Nebraska-Western Iowa Health Care Center and the University of Nebraska Medical Center, Omaha, NE, USA. · Division of Rheumatology, University of Pennsylvania, Philadelphia, and Corporal Michael C. Crescenz VA Medical Center, Philadelphia, PA, USA. ·Clin Exp Rheumatol · Pubmed #30418120.

ABSTRACT: OBJECTIVES: Obese patients with rheumatoid arthritis (RA) may be more likely to discontinue therapy than non-obese patients, possibly signifying a more refractory phenotype. The purpose of this study was to examine the association between body mass index (BMI) and discontinuation rates for different RA treatments accounting for confounding factors. METHODS: Veterans Affairs administrative databases were used to define initial courses of methotrexate (MTX), hydroxychloroquine, sulfasalazine, prednisone, and self-injectable tumour necrosis factor inhibitors (TNFi). Discontinuation was defined as a lapse in drug refill >90 days. Using overweight BMI (25-30 kg/m2) as the referent group, multivariable Cox proportional hazards models were used to evaluate associations between BMI category and time to treatment discontinuation. RESULTS: There were 46,970 initial RA treatment courses identified from 2005-2014 among 23,669 Veterans with RA. In multivariable models, severe obesity (BMI >35 kg/m2), compared to overweight BMI, was not associated with treatment discontinuation with the exception of prednisone [HR 1.10 (1.04, 1.17) p<0.001]. Patients with low (<20 kg/m2) and normal BMI (20-25 kg/m2) were more likely to discontinue MTX, TNFi, and HCQ compared to overweight patients. Other factors associated with earlier MTX and/or TNFi discontinuation included female sex, black race, greater comorbidity, depression, malignancy, congestive heart failure, current smoking, and more recent calendar year. CONCLUSIONS: Obesity was not associated with therapy discontinuation among veterans with RA after accounting for confounding factors, suggesting that obesity is not a biological mediator of more refractory disease. Conversely, low BMI, comorbidity, and depression were identified as important predictors of drug discontinuation.

17 Article Chronic lung disease in U.S. Veterans with rheumatoid arthritis and the impact on survival. 2018

England, Bryant R / Sayles, Harlan / Michaud, Kaleb / Thiele, Geoffrey M / Poole, Jill A / Caplan, Liron / Sauer, Brian C / Cannon, Grant W / Reimold, Andreas / Kerr, Gail S / Baker, Joshua F / Mikuls, Ted R. ·VA Nebraska-Western IA Health Care System, Omaha, NE, USA. bryant.england@unmc.edu. · Division of Rheumatology and Immunology, Department of Internal Medicine, University of Nebraska Medical Center, 986270 Nebraska Med Center, Omaha, Nebraska, United States. bryant.england@unmc.edu. · Division of Rheumatology and Immunology, Department of Internal Medicine, University of Nebraska Medical Center, 986270 Nebraska Med Center, Omaha, Nebraska, United States. · Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA. · National Data Bank for Rheumatic Diseases, Wichita, KS, USA. · VA Nebraska-Western IA Health Care System, Omaha, NE, USA. · Department of Internal Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Nebraska Medical Center, Omaha, NE, USA. · Denver VA and University of Colorado, Denver, CO, USA. · VA Salt Lake City and University of Utah, Salt Lake City, UT, USA. · Dallas VA and University of Texas Southwestern, Dallas, TX, USA. · Washington DC VAMC, Georgetown and Howard University, Washington, DC, USA. · Corporal Michael J. Crescenz VA and University of Pennsylvania, Philadelphia, PA, USA. ·Clin Rheumatol · Pubmed #30280369.

ABSTRACT: Assess the impact of chronic lung diseases (CLD) on survival in rheumatoid arthritis (RA). Among participants in the Veterans Affairs Rheumatoid Arthritis (VARA) Registry, a prospective cohort of U.S. Veterans with RA, we identified CLD and cardiovascular disease (CVD) using administrative and registry data. Demographics, smoking status, RA characteristics including Disease Activity Score in 28 joints (DAS28), and disease-modifying anti-rheumatic drug (DMARD) use were obtained from registry data, which were linked to the National Death Index to obtain vital status. We evaluated associations of CLD with survival using the multivariable Cox regression models. Among a large (n = 2053), male-predominant (91%) RA cohort, 554 (27%) had CLD at enrollment. Mortality risk was increased 1.51-fold (95% CI 1.26-1.81) in RA patients with CLD after multivariable adjustment, a risk that was similar to that observed with CVD (HR CLD alone 1.46 [1.03-2.06]; CVD alone 1.62 [1.35-1.94]). Survival was significantly reduced in those with interstitial lung disease (ILD) as well as other forms of CLD. Mortality risk with methotrexate and biologic use was not different in those with CLD compared to those without (p interaction ≥ 0.15) using multiple exposure definitions and propensity score adjustment. Mortality risk is significantly increased in RA patients with CLD. This risk is attributable not only to ILD but also to other chronic lung conditions and does not appear to be substantially greater in those receiving methotrexate or biologic therapies. Comorbid lung disease should be targeted as a means of improving long-term outcomes in RA.

18 Article Development of a Janus Kinase Inhibitor Prodrug for the Treatment of Rheumatoid Arthritis. 2018

Wei, Xin / Wu, Jianbo / Zhao, Gang / Galdamez, Josselyn / Lele, Subodh M / Wang, Xiaoyan / Liu, Yanzhi / Soni, Dhruvkumar M / Purdue, P Edward / Mikuls, Ted R / Goldring, Steven R / Wang, Dong. ·Department of Pharmaceutical Sciences, College of Pharmacy , University of Nebraska Medical Center , Omaha , Nebraska 68198 , United States. · Hospital for Special Surgery , New York , New York 10021 , United States. · Department of Pathology and Microbiology, College of Medicine , University of Nebraska Medical Center , Omaha , Nebraska 68198 , United States. · Division of Rheumatology, Department of Internal Medicine, College of Medicine , University of Nebraska Medical Center , Omaha , Nebraska 68198 , United States. · Veterans Affairs Nebraska-Western Iowa Health Care System , Omaha , Nebraska 68105 , United States. ·Mol Pharm · Pubmed #29966420.

ABSTRACT: While highly efficacious in treating rheumatoid arthritis (RA), the approved Janus kinase (JAK) inhibitor, Tofacitinib (Tofa, CP-690 550), has dose-dependent toxicities that limit its clinical application. In this study, we have examined whether a prodrug design that targets arthritic joints would enhance Tofa's therapeutic efficacy, which may provide an opportunity for future development of safer Tofa dosing regimens. A prodrug of Tofa (P-Tofa) was synthesized by conjugating the drug to the N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer via an acid cleavable carbamate linker. The therapeutic efficacy of a single dose of P-Tofa was compared to the dose-equivalent daily oral administration of Tofa in an adjuvant-induced arthritis (AA) rat model. Saline treated AA rats and age-matched healthy rats were used as controls. Observational analyses support the superior and sustained efficacy of a single dose P-Tofa treatment compared to the dose-equivalent daily Tofa administration in ameliorating joint inflammation. Micro-CT and histological analyses demonstrated that the P-Tofa treatment provided a structural preservation of the joints better than that of the dose-equivalent Tofa. Optical imaging, immunohistochemistry, and fluorescence-activated cell sorting analyses attribute P-Tofa's superior therapeutic efficacy to its passive targeting to arthritic joints and inflammatory cell-mediated sequestration. In vitro cell culture studies reveal that the P-Tofa treatment produced sustained the inhibition of JAK/STAT6 signaling in IL-4-treated murine bone marrow macrophages, consistent with a gradual subcellular release of Tofa. Collectively, a HPMA-based nanoscale prodrug of P-Tofa has the potential to enhance the therapeutic efficacy and widen the therapeutic window of Tofa therapy in RA.

19 Article Obesity, Weight Loss, and Progression of Disability in Rheumatoid Arthritis. 2018

Baker, Joshua F / England, Bryant R / Mikuls, Ted R / Sayles, Harlan / Cannon, Grant W / Sauer, Brian C / George, Michael D / Caplan, Liron / Michaud, Kaleb. ·Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, and University of Pennsylvania, Philadelphia. · Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska. · Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska, University of Nebraska Medical Center, Omaha. · University of Nebraska Medical Center, Omaha. · Salt Lake City Veterans Affairs Medical Center, Salt Lake City, Utah, and University of Utah, Salt Lake City. · University of Pennsylvania, Philadelphia. · University of Nebraska Medical Center, Omaha, and the National Data Bank for Rheumatic Diseases, Wichita, Kansas. ·Arthritis Care Res (Hoboken) · Pubmed #29707921.

ABSTRACT: OBJECTIVE: Cross-sectional studies have demonstrated that obese patients with rheumatoid arthritis (RA) often report greater disability. The longitudinal effects of obesity, however, are not well-characterized. We evaluated associations between obesity, weight loss, and worsening of disability in patients of 2 large registry studies, which included patients who were followed for longer periods of time. METHODS: This study included patients with RA from the National Data Bank for Rheumatic Diseases (FORWARD) (n = 23,323) and the Veterans Affairs RA (VARA) registry study (n = 1,697). Results of the Health Assessment Questionnaire (HAQ) or Multidimensional HAQ (MD-HAQ) were recorded through follow-up. Significant worsening of disability was defined as an increase of >0.2 in HAQ or MD-HAQ scores. The Cox proportional hazards model was used to evaluate the risk of worsening of disability from baseline and to adjust for demographics, baseline disability, comorbidity, disease duration, and other disease features. RESULTS: At enrollment, disability scores were higher among severely obese patients compared to those who were overweight both in FORWARD (β = 0.17 [95% confidence interval (95% CI) 0.14, 0.20]; P < 0.001) and in the VARA registry (β = 0.17 [95% CI 0.074, 0.27]; P = 0.001). In multivariable models, patients who were severely obese at enrollment had a greater risk of progressive disability compared to overweight patients in FORWARD (HR 1.25 [95% CI 1.18, 1.33] P < 0.001) and in the VARA registry (HR 1.33 [95% CI 1.07, 1.66]; P = 0.01). Weight loss following enrollment was also associated with a greater risk in both cohorts. In the VARA registry, associations were independent of other clinical factors, including time-varying C-reactive protein and swollen joint count. CONCLUSION: Severe obesity is associated with a more rapid progression of disability in RA. Weight loss is also associated with worsening disability, possibly due to it being an indication of chronic illness and the development of age-related or disease-related frailty.

20 Article Malondialdehyde-acetaldehyde antibody concentrations in rheumatoid arthritis and other rheumatic conditions. 2018

Mikuls, Ted R / Duryee, Michael J / England, Bryant R / Anderson, Daniel R / Hearth-Holmes, Michelene / Su, Kaihong / Michaud, Kaleb / Payne, Jeffrey B / Sayles, Harlan / Hunter, Carlos / McGowan, Jacob D / Klassen, Lynell W / Thiele, Geoffrey M. ·Veterans Affairs (VA) Nebraska-Western Iowa Health Care System, Omaha, NE, United States; Department of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, United States. Electronic address: tmikuls@unmc.edu. · Veterans Affairs (VA) Nebraska-Western Iowa Health Care System, Omaha, NE, United States; Department of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, United States. · Department of Internal Medicine, Division of Cardiology, University of Nebraska Medical Center, Omaha, NE, United States. · Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, United States. · Department of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, United States; National Data Bank for Rheumatic Diseases, Wichita, KS, United States. · Department of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, United States; Department of Surgical Specialties, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE. · Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, United States. · Department of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, United States. ·Int Immunopharmacol · Pubmed #29414640.

ABSTRACT: OBJECTIVE: To compare anti-malondialdehyde-acetaldehyde (MAA) antibody concentrations between rheumatoid arthritis (RA) patients and healthy and rheumatic disease controls. METHODS: Anti-MAA antibody (IgA, IgM, IgG) was measured using ELISA and banked serum from patients with RA (n = 284), osteoarthritis (OA, n = 330), spondyloarthropathy (SpA, n = 50), and systemic lupus erythematosus (SLE, n = 88) as well as healthy controls (n = 82). Anti-MAA antibody concentrations and the frequency of positivity were compared across groups. Multivariable linear regression analysis limited to RA and OA patients (due to sample size and data availability) was used to identify factors associated with anti-MAA antibody concentrations. RESULTS: Although RA patients demonstrated among the highest circulating concentrations across isotypes, only IgA anti-MAA antibody was significantly higher than all other groups (p ≤ 0.02). Proportions (7% to 74%) of OA and SLE (less so for SpA) samples were positive for anti-MAA antibody, limiting the discriminatory capacity of anti-MAA antibody in RA (positive in 18% to 80%). In analyses limited to those with RA or OA, factors associated with higher anti-MAA antibody concentrations included RA case status, younger age (IgM), male sex (IgG), African American race (IgA, IgG) and current smoking (IgA). C-reactive protein levels and comorbidities were not associated with anti-MAA antibody concentrations. CONCLUSION: With the possible exception of the IgA isotype, serum anti-MAA antibodies measured with currently available assays do not appear to adequately discriminate RA from other rheumatic conditions. With the identification of specific proteins that are MAA-modified in diseased tissues and requisite assay refinement, anti-MAA antibody holds potential promise as a biomarker in RA.

21 Article Trends and Determinants of Osteoporosis Treatment and Screening in Patients With Rheumatoid Arthritis Compared to Osteoarthritis. 2018

Ozen, Gulsen / Kamen, Diane L / Mikuls, Ted R / England, Bryant R / Wolfe, Frederick / Michaud, Kaleb. ·University of Nebraska Medical Center, Omaha, and Marmara University, Istanbul, Turkey. · Medical University of South Carolina, Charleston. · University of Nebraska Medical Center and Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha. · National Data Bank for Rheumatic Diseases, Wichita, Kansas. · University of Nebraska Medical Center, Omaha, and National Data Bank for Rheumatic Diseases, Wichita, Kansas. ·Arthritis Care Res (Hoboken) · Pubmed #28771973.

ABSTRACT: OBJECTIVE: To profile osteoporosis (OP) care in patients with rheumatoid arthritis (RA) over the past decade. METHODS: Patients with RA or osteoarthritis (OA) were followed from 2003 through 2014. OP care was defined as receipt of OP treatment (with the exception of calcium/vitamin D) or screening (OPTS). Adjusted trends over followup, and the factors associated with OP care, were examined using multivariable Cox proportional hazards. RESULTS: OPTS was reported in 67.4% of 11,669 RA patients and in 64.6% of 2,829 OA patients during a median (interquartile range) 5.5 (2-9) years of followup. In patients for whom treatment was recommended by the 2010 American College of Rheumatology (ACR) glucocorticoid-induced OP (GIOP) guidelines (48.4% of RA patients and 17.6% of OA patients), approximately 55% overall reported OP medication use. RA patients were not more likely to undergo OPTS compared to OA patients (hazard ratio 1.04 [95% confidence interval 0.94-1.15]). Adjusted models showed a stable trend for OPTS between 2004 and 2008 compared to 2003, with a significant downward trend after 2008 in both RA and OA patients. Factors associated with receipt of OP care in RA patients were older age, postmenopausal state, prior fragility fracture or diagnosis of OP, any duration of glucocorticoid treatment, and use of biologic agents. CONCLUSION: Approximately half of RA patients for whom treatment was indicated never received an OP medication. OP care in RA patients was not better than in OA patients, and the relative risk of the application of this care has been decreasing in RA and OA patients since 2008 without improvement after the release of the 2010 ACR GIOP guideline.

22 Article Body Mass Index, Weight Loss, and Cause-Specific Mortality in Rheumatoid Arthritis. 2018

England, Bryant R / Baker, Joshua F / Sayles, Harlan / Michaud, Kaleb / Caplan, Liron / Davis, Lisa A / Cannon, Grant W / Sauer, Brian C / Solow, E Blair / Reimold, Andreas M / Kerr, Gail S / Mikuls, Ted R. ·VA Nebraska-Western Iowa Healthcare System, and University of Nebraska Medical Center, Omaha. · Philadelphia VA and University of Pennsylvania, Philadelphia. · University of Nebraska Medical Center, Omaha, and National Data Bank for Rheumatic Diseases, Wichita, Kansas. · Denver VA Medical Center, and University of Colorado, Denver. · Denver VA Medical Center, University of Colorado, and Denver Health Medical Center, Denver. · VA Salt Lake City Healthcare System, and University of Utah, Salt Lake City. · Dallas VA and University of Texas Southwestern, Dallas. · VA Medical Center, Georgetown University, and Howard University, Washington, DC. ·Arthritis Care Res (Hoboken) · Pubmed #28426913.

ABSTRACT: OBJECTIVE: To examine associations of body mass index (BMI) and weight loss with cause-specific mortality in rheumatoid arthritis (RA). METHODS: A cohort of US veterans with RA was followed until death or through 2013. BMI was categorized as underweight, normal, overweight, and obese. Weight loss was calculated as the 1) annualized rate of change over the preceding 13 months, and 2) cumulative percent. Vital status and cause of death were obtained from the National Death Index. Multivariable competing-risks regression models were utilized to assess the time-varying associations of BMI and weight loss with cause-specific mortality. RESULTS: Among 1,600 participants and 5,789 patient-years of followup, 303 deaths occurred (95 cardiovascular, 74 cancer, and 46 respiratory). The highest weight-loss rate and weight-loss percent were associated with a higher risk of cardiovascular mortality (rate: subdistribution hazard ratio [sHR] 2.27 [95% confidence interval (95% CI) 1.61-3.19]; percent: sHR 2.31 [95% CI 1.06-5.01]) and cancer mortality (rate: sHR 2.36 [95% CI 1.11-5.01]; percent: sHR 1.90 [95% CI 1.00-3.62]). Overweight BMI was protective of cardiovascular mortality (sHR 0.59 [95% CI 0.38-0.91]), while underweight BMI was associated with a near 3-fold increased risk of respiratory mortality (sHR 2.93 [95% CI 1.28-6.67]). Incorporation of time-varying BMI and weight loss in the same models did not substantially alter individual associations for cardiovascular and cancer mortality, but an association between weight-loss percentage and respiratory mortality was attenuated after BMI adjustment. CONCLUSION: Both BMI and weight loss are predictors of cause-specific mortality in RA. Weight loss is a strong predictor of cardiovascular and cancer mortality, while underweight BMI is a stronger predictor of respiratory mortality.

23 Article Association of Distinct Fine Specificities of Anti-Citrullinated Peptide Antibodies With Elevated Immune Responses to Prevotella intermedia in a Subgroup of Patients With Rheumatoid Arthritis and Periodontitis. 2017

Schwenzer, Anja / Quirke, Anne-Marie / Marzeda, Anna M / Wong, Alicia / Montgomery, Anna B / Sayles, Harlan R / Eick, Sigrun / Gawron, Katarzyna / Chomyszyn-Gajewska, Maria / Łazarz-Bartyzel, Katarzyna / Davis, Simon / Potempa, Jan / Kessler, Benedikt M / Fischer, Roman / Venables, Patrick J / Payne, Jeffrey B / Mikuls, Ted R / Midwood, Kim S. ·University of Oxford, Oxford, UK. · University of Oxford, Oxford, UK, and Jagiellonian University, Krakow, Poland. · Jagiellonian University, Krakow, Poland. · University of Nebraska Medical Center, Omaha. · University of Bern, Bern, Switzerland. · Jagiellonian University, Krakow, Poland, and University of Louisville, Louisville, Kentucky. · University of Nebraska Medical Center, Lincoln. · University of Nebraska Medical Center and Nebraska-Western Iowa Health Care System, Omaha. ·Arthritis Rheumatol · Pubmed #29084415.

ABSTRACT: OBJECTIVE: In addition to the long-established link with smoking, periodontitis (PD) is a risk factor for rheumatoid arthritis (RA). This study was undertaken to elucidate the mechanism by which PD could induce antibodies to citrullinated peptides (ACPAs), by examining the antibody response to a novel citrullinated peptide of cytokeratin 13 (CK-13) identified in gingival crevicular fluid (GCF), and comparing the response to 4 other citrullinated peptides in patients with RA who were well-characterized for PD and smoking. METHODS: The citrullinomes of GCF and periodontal tissue from patients with PD were mapped by mass spectrometry. ACPAs of CK13 (cCK13), tenascin-C (cTNC5), vimentin (cVIM), α-enolase (CEP-1), and fibrinogen β (cFIBβ) were examined by enzyme-linked immunosorbent assay in patients with RA (n = 287) and patients with osteoarthritis (n = 330), and cross-reactivity was assessed by inhibition assays. RESULTS: A novel citrullinated peptide cCK13-1 ( CONCLUSION: This study identifies 2 groups of ACPA fine specificities associated with different RA risk factors. One is predominantly linked to smoking and shared epitope, and the other links anti-cTNC5 and cCK13-1 to infection with the periodontal pathogen P intermedia.

24 Article Enrichment of malondialdehyde-acetaldehyde antibody in the rheumatoid arthritis joint. 2017

Mikuls, Ted R / Duryee, Michael J / Rahman, Rafid / Anderson, Daniel R / Sayles, Harlan R / Hollins, Andrew / Michaud, Kaleb / Wolfe, Frederick / Thiele, Geoffrey E / Sokolove, Jeremy / Robinson, William H / Lingampalli, Nithya / Nicholas, Anthony P / Talmon, Geoffrey A / Su, Kaihong / Zimmerman, Matthew C / Klassen, Lynell W / Thiele, Geoffrey M. ·Veteran Affairs Nebraska-Western Iowa Health Care System. · Department of Internal Medicine, Division of Cardiovascular Medicine. · College of Public Health, Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE. · National Data Bank for Rheumatic Diseases, Wichita, KS. · VA Palo Alto Healthcare Center and Division of Immunology and Rheumatology, Stanford University School of Medicine, Palo Alto. · VA Palo Alto Healthcare System and Department of Medicine, Division of Rheumatology, Stanford University, Stanford, CA. · Department of Neurology, University of Alabama at Birmingham, Birmingham, AL. · Department of Pathology and Microbiology. · Department of Cellular & Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA. ·Rheumatology (Oxford) · Pubmed #28957552.

ABSTRACT: Objective: To characterize the expression of malondialdehdye-acetaldehyde (MAA) adducts and anti-MAA antibody in articular tissues and serum of patients with RA. Methods: Paired sera and SF were examined from 29 RA and 13 OA patients. Anti-MAA antibody, RF, ACPA and total immunoglobulin were quantified. SF-serum measures were compared within and between disease groups. The presence and co-localization of MAA, citrulline and select leukocyte antigens in RA and OA synovial tissues were examined using immunohistochemistry. Results: Circulating and SF anti-MAA antibody concentrations were higher in RA vs OA by 1.5- to 5-fold. IgG (P < 0.001), IgM (P = 0.006) and IgA (P = 0.036) anti-MAA antibodies were higher in paired RA SF than serum, differences not observed for total immunoglobulin, RF or ACPA. In RA synovial tissues, co-localization of MAA with citrulline and CD19+ or CD27+ B cells was demonstrated and was much higher in magnitude than MAA or citrulline co-localization with T cells, monocytes, macrophages or dendritic cells (P < 0.01). Conclusion: Anti-MAA antibodies are present in higher concentrations in the RA joint compared with sera, a finding not observed for other disease-related autoantibodies. Co-localization of MAA and citrulline with mature B cells, coupled with the local enrichment of anti-MAA immune responses, implicates MAA-adduct formation in local autoantibody production.

25 Article Comment on: Increased inflammation and disease activity among current cigarette smokers with rheumatoid arthritis: a cross-sectional analysis of US veterans: reply. 2017

Sokolove, Jeremy / Sayles, Harlan / Mikuls, Ted. ·Veterans Affairs Palo Alto Health Care. · Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Palo Alto, CA. · Veterans Affairs Nebraska Western-Iowa Health Care System. · Nebraska Arthritis Outcomes Research Center, University of Nebraska Medical Center, Omaha, NE, USA. ·Rheumatology (Oxford) · Pubmed #28575469.

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