Comprehensive Profiling of the Rheumatoid Arthritis Antibody Repertoire
ConclusionComprehensive antibody profiling using a high ‐density peptide array not only identified novel RA‐specific epitopes but also allowed us to construct a novel diagnostic biomarker that is as specific as and more sensitive than the Abnova CCP2 assay. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 29, 2019 Category: Rheumatology Authors: Ken C. Lo, Eric Sullivan, Ryan M. Bannen, Huiyan Jin, Mark Rowe, Hanying Li, Richard S. Pinapati, Adam J. Cartwright, John C. Tan, Jigar Patel, Edward C. Keystone, Katherine A. Siminovitch Tags: Original Article Source Type: research

Scrutinizing the Frustrating Cost of Drugs: How Rebates and Step Therapy Inflate Medicare Part D Prices —and Possible Reforms
Arthritis&Rheumatology, EarlyView. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 29, 2019 Category: Rheumatology Authors: Angus B. Worthing Tags: Editorial Source Type: research

Unresolved questions on the relationship between EZH2 and lupus: comment on the article by Rohraff et al
Arthritis&Rheumatology, EarlyView. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 29, 2019 Category: Rheumatology Authors: Wang ‐Dong Xu, An‐Fang Huang Tags: Letters Source Type: research

Myositis Autoantibodies: A Comparison of Results From the Oklahoma Medical Research Foundation Myositis Panel to the Euroimmun Research Line Blot
Arthritis&Rheumatology, Volume 72, Issue 1, Page 192-194, January 2020. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Authors: Christopher A. Mecoli, Jemima Albayda, Eleni Tiniakou, Julie J. Paik, Umar Zahid, Sonye K. Danoff, Livia Casciola ‐Rosen, Maria Casal‐Dominguez, Katherine Pak, Iago Pinal‐Fernandez, Andrew L. Mammen, Lisa Christopher‐Stine Tags: Concise Communication Source Type: research

Issue Information
Arthritis&Rheumatology, Volume 72, Issue 1, January 2020. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Tags: Issue Information Source Type: research

Clinical Connections
Arthritis&Rheumatology, Volume 72, Issue 1, January 2020. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Tags: Clinical Connections Source Type: research

In This Issue
Arthritis&Rheumatology, Volume 72, Issue 1, January 2020. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Tags: In This Issue Source Type: research

When Randomized Clinical Trials and Real ‐World Evidence Say the Same: Tocilizumab and Its Cardiovascular Safety
Arthritis&Rheumatology, Volume 72, Issue 1, Page 4-6, January 2020. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Authors: Seoyoung C. Kim, Sebastian Schneeweiss Tags: Editorial Source Type: research

Classification of IgG4 ‐Related Disease: A Medical Marvel of Our Time
Arthritis&Rheumatology, Volume 72, Issue 1, Page 1-3, January 2020. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Authors: Sindhu R. Johnson, Arthur Bookman Tags: Editorial Source Type: research

ACR Announcements
Arthritis&Rheumatology, Volume 72, Issue 1, January 2020. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Tags: ACR Announcements Source Type: research

Cardiovascular Safety of Tocilizumab Versus Etanercept in Rheumatoid Arthritis: A Randomized Controlled Trial
ObjectiveTo assess the risk of major adverse cardiovascular events (MACE) in patients with rheumatoid arthritis (RA) treated with tocilizumab compared to those treated with the tumor necrosis factor inhibitor etanercept.MethodsThis randomized, open ‐label, parallel‐group trial enrolled patients with active seropositive RA (n = 3,080) who had an inadequate response to conventional synthetic disease‐modifying antirheumatic drugs and who had at least 1 cardiovascular (CV) risk factor. Patients were randomly assigned 1:1 to receive open‐l abel tocilizumab at 8 mg/kg/month or etanercept at 50 mg/week. All pati...
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Authors: Jon T. Giles, Naveed Sattar, Sherine Gabriel, Paul M. Ridker, Steffen Gay, Charles Warne, David Musselman, Laura Brockwell, Emma Shittu, Micki Klearman, Thomas R. Fleming Tags: Original Article Source Type: research

Dipeptidylpeptidase 4 as a Marker of Activated Fibroblasts and a Potential Target for the Treatment of Fibrosis in Systemic Sclerosis
ObjectiveExpression of dipeptidylpeptidase 4 (DPP ‐4) identifies a dermal fibroblast lineage involved in scarring during wound healing. The role of DDP‐4 in tissue fibrosis is, however, unknown. The aim of the present study was to evaluate DPP‐4 as a potential target for the treatment of fibrosis in patients with systemic sclerosis (SSc).MethodsExpression of DPP ‐4 in skin biopsy samples and dermal fibroblasts was analyzed by real‐time polymerase chain reaction, immunofluorescence, and Western blot analyses. The activity of DPP‐4 was modulated by overexpression, knockdown, and pharmacologic inhibition of DPP4 u...
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Authors: Alina Soare, Hermina A. Gy örfi, Alexandru E. Matei, Clara Dees, Simon Rauber, Thomas Wohlfahrt, Chih‐Wei Chen, Ingo Ludolph, Raymund E. Horch, Tobias Bäuerle, Stephan Hörsten, Carina Mihai, Oliver Distler, Andreas Ramming, Georg Schett Tags: Original Article Source Type: research

Increased Adhesive Potential of Antiphospholipid Syndrome Neutrophils Mediated by β2 Integrin Mac‐1
This study was undertaken to investigate the extent to which antiphospholipid syndrome (APS) neutrophils adhere to resting endothelial cells under physiologic flow conditions and the surface molecules required for that adhesion.MethodsPatients with primary APS (n = 43), patients with a history of venous thrombosis but negative test results for antiphospholipid antibodies (n = 11), and healthy controls (n = 38) were studied. Cells were introduced into a flow chamber and perfused across resting human umbilical vein endothelial cells (HUVECs). Surface adhesion molecules were quantified by flow cytometry. Neutrophil extracellu...
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Authors: Gautam Sule, William J. Kelley, Kelsey Gockman, Srilakshmi Yalavarthi, Andrew P. Vreede, Alison L. Banka, Paula L. Bockenstedt, Omolola Eniola ‐Adefeso, Jason S. Knight Tags: Original Article Source Type: research

Abatacept in Early Diffuse Cutaneous Systemic Sclerosis: Results of a Phase II Investigator ‐Initiated, Multicenter, Double‐Blind, Randomized, Placebo‐Controlled Trial
This study was undertaken to assess the safety and efficacy of abatacept in patients with diffuse cutaneous systemic sclerosis (dcSSc).MethodsIn this 12 ‐month, randomized, double‐blind, placebo‐controlled trial, participants were randomized 1:1 to receive either subcutaneous abatacept 125 mg or matching placebo, stratified by duration of dcSSc. Escape therapy was allowed at 6 months for worsening disease. The coprimary end points were change in the modified Rodnan skin thickness score (MRSS) compared to baseline and safety over 12 months. Differences in longitudinal outcomes were assessed according to treatment usin...
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Authors: Dinesh Khanna, Cathie Spino, Sindhu Johnson, Lorinda Chung, Michael L. Whitfield, Christopher P. Denton, Veronica Berrocal, Jennifer Franks, Bhavan Mehta, Jerry Molitor, Virginia D. Steen, Robert Lafyatis, Robert W. Simms, Anna Gill, Suzanne Tags: Original Article Source Type: research

Differential Responsiveness of Monocyte and Macrophage Subsets to Interferon
This study was undertaken to examine an unexpected influence of monocyte/macrophages on the IFN signature.MethodsProinflammatory (classic) and antiinflammatory (nonclassic) monocyte/macrophages were sorted from mice and analyzed by RNA sequencing and quantitative polymerase chain reaction (qPCR). Type I IFN ‐α/β/ω receptor (IFNAR‐1) expression was determined by qPCR and flow cytometry. Macrophages were stimulated in vitro with IFNα, and pSTAT1was measured.ResultsTranscriptional profiling of peritoneal macrophages from mice with pristane ‐induced SLE unexpectedly indicated a strong IFN signature...
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Authors: Shuhong Han, Haoyang Zhuang, Pui Y. Lee, Mingjia Li, Lijun Yang, Peter A. Nigrovic, Westley H. Reeves Tags: Original Article Source Type: research

Effects of Conventional Uric Acid –Lowering Therapy on Monosodium Urate Crystal Deposits
This study was undertaken to analyze the effect of lifestyle measures and conventional urate‐lowering therapy on MSU deposits in patients with gout.MethodsIn this prospective study, subjects with gout according to the American College of Rheumatology/European League Against Rheumatism classification criteria and presence of MSU deposits seen on dual ‐energy computed tomography (DECT) scans received either lifestyle intervention or conventional urate‐lowering therapy for a mean period of 18 months before a follow‐up DECT scan. Detected MSU deposits were quantified by volumetric measurement and validated by semiquant...
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Authors: Hanna Ellmann, Sara Bayat, Elizabeth Araujo, Bernhard Manger, Arnd Kleyer, Alexander Cavallaro, Michael Lell, Hannah Schenker, David Simon, Koray Tascilar, Herbert S. B. Baraf, Georg Schett, J ürgen Rech Tags: Original Article Source Type: research

High Prevalence and Disease Correlation of Autoantibodies Against p40 Encoded by Long Interspersed Nuclear Elements in Systemic Lupus Erythematosus
This study was undertaken to investigate whether SLE patients also produce autoantibodies against LINE‐1 p40.MethodsHighly purified p40 protein was used to quantitate IgG autoantibodies in serum from 172 SLE patients and from disease controls and age ‐matched healthy subjects by immunoblotting and enzyme‐linked immunosorbent assay (ELISA). Preparations of p40 that also contained associated proteins were analyzed by immunoblotting with patient sera.ResultsAntibodies reactive with p40 were detected in the majority of patients and many healthy controls. Their levels were higher in patients with SLE, but not those with s...
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Authors: Victoria Carter, John LaCava, Martin S. Taylor, Shu Ying Liang, Cecilia Mustelin, Kennedy C. Ukadike, Anders Bengtsson, Christian Lood, Tomas Mustelin Tags: Original Article Source Type: research

Catastrophic Antiphospholipid Syndrome –Associated Nephropathy in a Systemic Lupus Erythematosus Patient Without Lupus Nephritis
Arthritis&Rheumatology, Volume 72, Issue 1, Page 149-149, January 2020. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Authors: Rajib K. Gupta, Eric Liu, Eduardo Bonilla, Hind Elsaid Tags: Clinical Image Source Type: research

Reactivity of IgG with the p40 protein encoded by the long interspersed nuclear element 1 retroelement: comment on the article by Carter et al
Arthritis&Rheumatology, EarlyView. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Authors: Mary K. Crow Tags: Letters Source Type: research

Issue Information
Arthritis&Rheumatology, Volume 72, Issue 1, January 2020. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Tags: Issue Information Source Type: research

Clinical Connections
Arthritis&Rheumatology, Volume 72, Issue 1, January 2020. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Tags: Clinical Connections Source Type: research

In This Issue
Arthritis&Rheumatology, Volume 72, Issue 1, January 2020. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Tags: In This Issue Source Type: research

Classification of IgG4 ‐Related Disease: A Medical Marvel of Our Time
Arthritis&Rheumatology, Volume 72, Issue 1, Page 1-3, January 2020. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Authors: Sindhu R. Johnson, Arthur Bookman Tags: Editorial Source Type: research

ACR Announcements
Arthritis&Rheumatology, Volume 72, Issue 1, January 2020. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Tags: ACR Announcements Source Type: research

Dipeptidylpeptidase 4 as a Marker of Activated Fibroblasts and a Potential Target for the Treatment of Fibrosis in Systemic Sclerosis
ObjectiveExpression of dipeptidylpeptidase 4 (DPP ‐4) identifies a dermal fibroblast lineage involved in scarring during wound healing. The role of DDP‐4 in tissue fibrosis is, however, unknown. The aim of the present study was to evaluate DPP‐4 as a potential target for the treatment of fibrosis in patients with systemic sclerosis (SSc).MethodsExpression of DPP ‐4 in skin biopsy samples and dermal fibroblasts was analyzed by real‐time polymerase chain reaction, immunofluorescence, and Western blot analyses. The activity of DPP‐4 was modulated by overexpression, knockdown, and pharmacologic inhibition of DPP4 u...
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Authors: Alina Soare, Hermina A. Gy örfi, Alexandru E. Matei, Clara Dees, Simon Rauber, Thomas Wohlfahrt, Chih‐Wei Chen, Ingo Ludolph, Raymund E. Horch, Tobias Bäuerle, Stephan Hörsten, Carina Mihai, Oliver Distler, Andreas Ramming, Georg Schett Tags: Original Article Source Type: research

Increased Adhesive Potential of Antiphospholipid Syndrome Neutrophils Mediated by β2 Integrin Mac‐1
This study was undertaken to investigate the extent to which antiphospholipid syndrome (APS) neutrophils adhere to resting endothelial cells under physiologic flow conditions and the surface molecules required for that adhesion.MethodsPatients with primary APS (n = 43), patients with a history of venous thrombosis but negative test results for antiphospholipid antibodies (n = 11), and healthy controls (n = 38) were studied. Cells were introduced into a flow chamber and perfused across resting human umbilical vein endothelial cells (HUVECs). Surface adhesion molecules were quantified by flow cytometry. Neutrophil extracellu...
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Authors: Gautam Sule, William J. Kelley, Kelsey Gockman, Srilakshmi Yalavarthi, Andrew P. Vreede, Alison L. Banka, Paula L. Bockenstedt, Omolola Eniola ‐Adefeso, Jason S. Knight Tags: Original Article Source Type: research

Catastrophic Antiphospholipid Syndrome –Associated Nephropathy in a Systemic Lupus Erythematosus Patient Without Lupus Nephritis
Arthritis&Rheumatology, Volume 72, Issue 1, Page 149-149, January 2020. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Authors: Rajib K. Gupta, Eric Liu, Eduardo Bonilla, Hind Elsaid Tags: Clinical Image Source Type: research

Reactivity of IgG with the p40 protein encoded by the long interspersed nuclear element 1 retroelement: comment on the article by Carter et al
Arthritis&Rheumatology, EarlyView. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 27, 2019 Category: Rheumatology Authors: Mary K. Crow Tags: Letters Source Type: research

PARP9 enhances infiltration of mononuclear cells in pSS through IFIT1 ‐mediated upregulation of CXCL10
ConclusionThis study is the first to implicate PARP9 as a regulator of infiltration of mononuclear cells in pSS progression and reveal that PARP9 increased CXCL10 expression through upregulating IFIT1 which is mediated by phosphorylation of STAT1. PARP9 might therefore be a novel therapeutic target for pSS. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 26, 2019 Category: Rheumatology Authors: Qingqing Tian, Han Zhao, Hanzhi Ling, Li Sun, Chipeng Xiao, Guoyu Yin, Xiaobing Wang, Gan Wu, Chenglin Yang, Mu Chen, Shengwei Jin, Xinyu Yang, Jianguang Wang Tags: FULL LENGTH Source Type: research

Development of Murine Systemic Lupus Erythematosus in the Absence of BAFF
ObjectiveTo determine whether systemic lupus erythematosus (SLE) can develop in the absence of BAFF in an SLE ‐prone host.MethodsStarting with C57BL/6 mice that express a humanBCL2 transgene (Tg) in their B cells (thereby rendering B cell survival largely independent of BAFF ‐triggered signals), we introgressed this Tg into NZM 2328 mice genetically deficient in BAFF (NZM.Baff−/−) to generate NZM.Baff−/−.Bcl2Tg mice. Expression of human Bcl ‐2 and lymphocyte profiles were assessed by fluorescence‐activated cell sorting, and serologic profiles were determined by enzyme‐linked immunosorbent ...
Source: Arthritis and Rheumatology - December 26, 2019 Category: Rheumatology Authors: William Stohl, Ning Yu, Samantha Chalmers, Chaim Putterman, Chaim O. Jacob Tags: Original Article Source Type: research

Timing of Elevations of Autoantibody Isotypes Prior to Diagnosis of Rheumatoid Arthritis
ConclusionDifferences in patterns of elevations of autoantibody isotypes have implications for understanding the pathophysiology of RA development. These include understanding what factors drive initial autoantibody elevations compared to what factors (including mucosal) drive later increases in autoantibody levels and a transition to clinically apparent RA, and how pre ‐RA endotypes may influence post–RA diagnosis phenotypes. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 26, 2019 Category: Rheumatology Authors: Lindsay B. Kelmenson, Brandie D. Wagner, Bryan K. McNair, Ashley Frazer ‐Abel, M. Kristen Demoruelle, Dylan T. Bergstedt, Marie L. Feser, Laura K. Moss, Mark C. Parish, Elizabeth A. Mewshaw, Ted R. Mikuls, Jess D. Edison, V. Michael Holers, Tags: Original Article Source Type: research

Benefit of Anakinra in Treating Pediatric Secondary Hemophagocytic Lymphohistiocytosis
ObjectiveTo assess the benefit of the recombinant human interleukin ‐1 receptor antagonist anakinra in treating pediatric patients with secondary hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) associated with rheumatic and nonrheumatic conditions.MethodsA retrospective chart review of all anakinra ‐treated patients with secondary HLH/MAS was performed at Children's of Alabama from January 2008 through December 2016. Demographic, clinical, laboratory, and genetic characteristics, outcomes data, and information on concurrent treatments were collected from the records and analyzed using appr...
Source: Arthritis and Rheumatology - December 26, 2019 Category: Rheumatology Authors: Esraa M. Eloseily, Peter Weiser, Courtney B. Crayne, Hilary Haines, Melissa L. Mannion, Matthew L. Stoll, Timothy Beukelman, T. Prescott Atkinson, Randy Q. Cron Tags: Original Article Source Type: research

Clinical Images: Teenaged boy with lipoma arborescens of the knee and elbow and presumed juvenile idiopathic arthritis
Arthritis&Rheumatology, EarlyView. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 26, 2019 Category: Rheumatology Authors: Cody S. Dail, Kelly R. Dietz, Michael A. Murati, Colleen K. Correll Tags: Clinical Image Source Type: research

Using Transitional Changes on High ‐Resolution Computed Tomography to Monitor the Impact of Cyclophosphamide or Mycophenolate Mofetil on Systemic Sclerosis–Related Interstitial Lung Disease
ObjectiveTo examine changes in the extent of specific patterns of interstitial lung disease (ILD) as they transition from one pattern to another in response to immunosuppressive therapy in systemic sclerosis –related ILD (SSc‐ILD).MethodsWe evaluated changes in the quantitative extent of specific lung patterns of ILD using volumetric high ‐resolution computed tomography (HRCT) scans obtained at baseline and after 2 years of therapy in patients treated with either cyclophosphamide (CYC) for 1 year or mycophenolate mofetil (MMF) for 2 years in Scleroderma Lung Study II. ILD patterns included lung fibrosis, ground g...
Source: Arthritis and Rheumatology - December 26, 2019 Category: Rheumatology Authors: Grace Hyun J. Kim, Donald P. Tashkin, Pechin Lo, Matthew S. Brown, Elizabeth R. Volkmann, David W. Gjertson, Dinesh Khanna, Robert M. Elashoff, Chi ‐Hong Tseng, Michael D. Roth, Jonathan G. Goldin Tags: Original Article Source Type: research

Population ‐Specific Patterns of Epigenetic Defects in the B Cell Lineage in Patients With Systemic Lupus Erythematosus
ObjectiveTo determine the stage of B cell development at which a systemic lupus erythematosus (SLE) –associated DNA methylation signature originates in African American (AA) and European American (EA) subjects, and to assess whether epigenetic defects in B cell development patterns could be predictive of SLE status in individual and mixed immune cell populations.MethodsB cells from AA patients (n = 31) and EA patients (n = 49) with or without SLE were sorted using fluorescence ‐activated cell sorting into 5 B cell subsets. DNA methylation, measured at ~460,000 CpG sites, was interrogated in each subset. Enrichment ...
Source: Arthritis and Rheumatology - December 26, 2019 Category: Rheumatology Authors: Megan E. Breitbach, Ryne C. Ramaker, Kevin Roberts, Robert P. Kimberly, Devin Absher Tags: Original Article Source Type: research

Timing of Elevations of Autoantibody Isotypes Prior to Diagnosis of Rheumatoid Arthritis
ConclusionDifferences in patterns of elevations of autoantibody isotypes have implications for understanding the pathophysiology of RA development. These include understanding what factors drive initial autoantibody elevations compared to what factors (including mucosal) drive later increases in autoantibody levels and a transition to clinically apparent RA, and how pre ‐RA endotypes may influence post–RA diagnosis phenotypes. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 26, 2019 Category: Rheumatology Authors: Lindsay B. Kelmenson, Brandie D. Wagner, Bryan K. McNair, Ashley Frazer ‐Abel, M. Kristen Demoruelle, Dylan T. Bergstedt, Marie L. Feser, Laura K. Moss, Mark C. Parish, Elizabeth A. Mewshaw, Ted R. Mikuls, Jess D. Edison, V. Michael Holers, Tags: Original Article Source Type: research

Clinical Images: Teenaged boy with lipoma arborescens of the knee and elbow and presumed juvenile idiopathic arthritis
Arthritis&Rheumatology, EarlyView. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 26, 2019 Category: Rheumatology Authors: Cody S. Dail, Kelly R. Dietz, Michael A. Murati, Colleen K. Correll Tags: Clinical Image Source Type: research

Using Transitional Changes on High ‐Resolution Computed Tomography to Monitor the Impact of Cyclophosphamide or Mycophenolate Mofetil on Systemic Sclerosis–Related Interstitial Lung Disease
ObjectiveTo examine changes in the extent of specific patterns of interstitial lung disease (ILD) as they transition from one pattern to another in response to immunosuppressive therapy in systemic sclerosis –related ILD (SSc‐ILD).MethodsWe evaluated changes in the quantitative extent of specific lung patterns of ILD using volumetric high ‐resolution computed tomography (HRCT) scans obtained at baseline and after 2 years of therapy in patients treated with either cyclophosphamide (CYC) for 1 year or mycophenolate mofetil (MMF) for 2 years in Scleroderma Lung Study II. ILD patterns included lung fibrosis, ground g...
Source: Arthritis and Rheumatology - December 26, 2019 Category: Rheumatology Authors: Grace Hyun J. Kim, Donald P. Tashkin, Pechin Lo, Matthew S. Brown, Elizabeth R. Volkmann, David W. Gjertson, Dinesh Khanna, Robert M. Elashoff, Chi ‐Hong Tseng, Michael D. Roth, Jonathan G. Goldin Tags: Original Article Source Type: research

Population ‐Specific Patterns of Epigenetic Defects in the B Cell Lineage in Patients With Systemic Lupus Erythematosus
ObjectiveTo determine the stage of B cell development at which a systemic lupus erythematosus (SLE) –associated DNA methylation signature originates in African American (AA) and European American (EA) subjects, and to assess whether epigenetic defects in B cell development patterns could be predictive of SLE status in individual and mixed immune cell populations.MethodsB cells from AA patients (n = 31) and EA patients (n = 49) with or without SLE were sorted using fluorescence ‐activated cell sorting into 5 B cell subsets. DNA methylation, measured at ~460,000 CpG sites, was interrogated in each subset. Enrichment ...
Source: Arthritis and Rheumatology - December 26, 2019 Category: Rheumatology Authors: Megan E. Breitbach, Ryne C. Ramaker, Kevin Roberts, Robert P. Kimberly, Devin Absher Tags: Original Article Source Type: research

PARP9 enhances infiltration of mononuclear cells in pSS through IFIT1 ‐mediated upregulation of CXCL10
ConclusionThis study is the first to implicate PARP9 as a regulator of infiltration of mononuclear cells in pSS progression and reveal that PARP9 increased CXCL10 expression through upregulating IFIT1 which is mediated by phosphorylation of STAT1. PARP9 might therefore be a novel therapeutic target for pSS. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 26, 2019 Category: Rheumatology Authors: Qingqing Tian, Han Zhao, Hanzhi Ling, Li Sun, Chipeng Xiao, Guoyu Yin, Xiaobing Wang, Gan Wu, Chenglin Yang, Mu Chen, Shengwei Jin, Xinyu Yang, Jianguang Wang Tags: FULL LENGTH Source Type: research

Peptidylarginine deiminase type 2 and 4 generate distinct patterns of rheumatoid arthritis autoantigens during perforin ‐induced cell damage
ConclusionThe cytotoxic granule ‐induced death pathway has the capacity to modify antigens by inducing hypercitrullination and antigen cleavage in target cells. Interestingly, among a large number of citrullinated proteins generated by PAD2 and PAD4 in cells, only few of these proteins are likely involved in the production of au toantibodies in RA. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 25, 2019 Category: Rheumatology Authors: Violeta Romero, Erika Darrah, Felipe Andrade Tags: BRIEF REPORT Source Type: research

Invited letter in response to the commentary “CD4+ T cells as key players in the immunopathology of Takayasu's arteritis”
AbstractWith great interest, we read the commentary by Dr. Ryu Watanabe. This commentary highlights the main findings of our recent study that demonstrates the biased mal ‐differentiation of Th1 and Th17 cells in patients with Takayasu's arteritis (TAK) and identifies mTORC1 hyperactivity as the T cell‐intrinsic mechanism [1]. Accordingly, targeting mTORC1 efficiently abrogates the pro‐inflammatory T cell differentiation and ameliorates arterial inflammation in humanized TAK model [1]. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 25, 2019 Category: Rheumatology Authors: Xiyu Liu, Wanwan Jiang, Ying Wang, Mengyao Sun, Zhibo Li, Zhenke Wen Tags: REPLY TO LETTER TO THE EDITOR Source Type: research

Form, Function, and Dysfunction: Airway Diseases Are Associated with Increased Risk for Rheumatoid Arthritis
AbstractRheumatoid arthritis (RA) risk is strongly influenced by environmental exposures and the organ with the largest interface with our environment is the lung. To effectively exchange oxygen for carbon dioxide, the lung must support a delicately thin mucosal border (2  µm) spread over 140 m2 (1). While ideal for gas exchange, the immensity of the lung ’s surface area makes it challenging to mitigate threats from inhaled pathogens and toxins while simultaneously promoting immunologic tolerance to harmless epitopes. A failure to maintain homeostatic host‐environment interactions along this mucosal bord...
Source: Arthritis and Rheumatology - December 25, 2019 Category: Rheumatology Authors: Maor Sauler Tags: EDITORIAL Source Type: research

CD4+ T cells as key players in the immunopathology of Takayasu's arteritis: Comments on the article by Zhang et al
AbstractI read the article by Zhang et al. published in this journal with great interest (1). They demonstrated that CD4+ T cells isolated from Takayasu's arteritis (TAK) are biased to differentiate into Th1 and Th17 cells because of mechanistic target of rapamycin complex 1 (mTORC1) hyperactivity. Subsequently, using human artery ‐NSG chimera model, they showed that mTORC1 inhibition, by either rapamycin or RNAi technology, effectively abrogated the mal‐differentiation of TAK CD4+ T cells and vascular inflammation. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 25, 2019 Category: Rheumatology Authors: Ryu Watanabe Tags: LETTER TO THE EDITOR Source Type: research

Peptidylarginine deiminase type 2 and 4 generate distinct patterns of rheumatoid arthritis autoantigens during perforin ‐induced cell damage
ConclusionThe cytotoxic granule ‐induced death pathway has the capacity to modify antigens by inducing hypercitrullination and antigen cleavage in target cells. Interestingly, among a large number of citrullinated proteins generated by PAD2 and PAD4 in cells, only few of these proteins are likely involved in the production of au toantibodies in RA. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 25, 2019 Category: Rheumatology Authors: Violeta Romero, Erika Darrah, Felipe Andrade Tags: BRIEF REPORT Source Type: research

Invited letter in response to the commentary “CD4+ T cells as key players in the immunopathology of Takayasu's arteritis”
AbstractWith great interest, we read the commentary by Dr. Ryu Watanabe. This commentary highlights the main findings of our recent study that demonstrates the biased mal ‐differentiation of Th1 and Th17 cells in patients with Takayasu's arteritis (TAK) and identifies mTORC1 hyperactivity as the T cell‐intrinsic mechanism [1]. Accordingly, targeting mTORC1 efficiently abrogates the pro‐inflammatory T cell differentiation and ameliorates arterial inflammation in humanized TAK model [1]. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 25, 2019 Category: Rheumatology Authors: Xiyu Liu, Wanwan Jiang, Ying Wang, Mengyao Sun, Zhibo Li, Zhenke Wen Tags: REPLY TO LETTER TO THE EDITOR Source Type: research

Form, Function, and Dysfunction: Airway Diseases Are Associated with Increased Risk for Rheumatoid Arthritis
AbstractRheumatoid arthritis (RA) risk is strongly influenced by environmental exposures and the organ with the largest interface with our environment is the lung. To effectively exchange oxygen for carbon dioxide, the lung must support a delicately thin mucosal border (2  µm) spread over 140 m2 (1). While ideal for gas exchange, the immensity of the lung ’s surface area makes it challenging to mitigate threats from inhaled pathogens and toxins while simultaneously promoting immunologic tolerance to harmless epitopes. A failure to maintain homeostatic host‐environment interactions along this mucosal bord...
Source: Arthritis and Rheumatology - December 25, 2019 Category: Rheumatology Authors: Maor Sauler Tags: EDITORIAL Source Type: research

CD4+ T cells as key players in the immunopathology of Takayasu's arteritis: Comments on the article by Zhang et al
AbstractI read the article by Zhang et al. published in this journal with great interest (1). They demonstrated that CD4+ T cells isolated from Takayasu's arteritis (TAK) are biased to differentiate into Th1 and Th17 cells because of mechanistic target of rapamycin complex 1 (mTORC1) hyperactivity. Subsequently, using human artery ‐NSG chimera model, they showed that mTORC1 inhibition, by either rapamycin or RNAi technology, effectively abrogated the mal‐differentiation of TAK CD4+ T cells and vascular inflammation. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - December 25, 2019 Category: Rheumatology Authors: Ryu Watanabe Tags: LETTER TO THE EDITOR Source Type: research

The leukotriene B4 ‐leukotriene B4 receptor 1 axis promotes myofibroblast differentiation and tissue fibrosis in systemic sclerosis
This study aimed to investigate the role of an inflammatory lipid mediator, leukotriene B4 (LTB4), and its receptor BLT1 in systemic sclerosis (SSc).MethodsSerum levels of LTB4 were compared in 64 subjects with SSc and 80 healthy controls (HC). Skin and lung sections were immunostained with leukotriene A4 hydrolase (LTA4H), the critical enzyme for LTB4 synthesis, and BLT1, in combination with different cell markers. The LTB4‐BLT1 axis was genetically or pharmacologically interrupted in mouse models of SSc induced by bleomycin or angiotensin II, or immunized with the DNA topoisomerase I. Immunoblotting was performed to ex...
Source: Arthritis and Rheumatology - December 23, 2019 Category: Rheumatology Authors: Minrui Liang, Jiaoyan Lv, Zhixing Jiang, Hang He, Chen Chen, Yinluo Xiong, Xiaoxia Zhu, Yu Xue, Yiyun Yu, Sen Yang, Lingbiao Wang, Wenjing Li, Ming Guan, Weiguo Wan, Rui He, Hejian Zou Tags: FULL LENGTH Source Type: research