MUC5B Promoter Variant and Survival in Rheumatoid Arthritis-Associated Interstitial Lung Disease.

Objective: Investigate the association between the MUC5B rs35705950 promoter variant and survival in RA-associated interstitial lung disease (RA-ILD).

Methods: We studied participants in the Veteran Affairs Rheumatoid Arthritis (VARA) registry with validated ILD diagnoses. Participants were followed until death or end of study period.

Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD): Update on Prevalence, Risk Factors, Pathogenesis, and Therapy.

Purpose Of Review: Rheumatoid arthritis is frequently complicated by interstitial lung disease (RA-ILD), an underappreciated contributor to excess morbidity and mortality. The true prevalence of RA-ILD is difficult to define given the variability in diagnostic criteria used. The lack of standardized screening methods, an incomplete understanding of disease pathogenesis, and dearth of validated biomarkers have limited the development of controlled clinical trials for this disease.

Relationship between Jo-1 B Cell Epitope Profile and Clinical Features of Anti-Synthetase Syndrome.

Objective: Anti-histidyl-transfer RNA synthetase (Jo-1) antibodies are associated with myositis as well as different extramuscular organ complications comprising the anti-synthetase syndrome. This study aimed to clarify the relationship between anti-Jo-1 epitope recognition patterns and specific clinical features of this syndrome.

Methods: B cell epitope mapping was performed via enzyme-linked immunosorbent assay in 180 patients who were anti-Jo-1 antibody-positive using overlapping peptides/protein fragments spanning the amino-terminal 151 amino acids of Jo-1 as substrate antigens.

Clinical features associated with the presence of anti-Ro52 and anti-Ro60 antibodies in Jo-1 antibody-positive anti-synthetase syndrome.

Introduction: Anti-SSA antibodies target two unrelated proteins, Ro52 (E3 ligase) and Ro60 (RNA binding protein). Previous studies indicate that anti-Ro52 antibodies are frequently associated with various myositis-specific autoantibodies (MSAs)-including anti-tRNA synthetase antibodies-and that the coexistence of MSAs and anti-Ro52 antibodies may portend worse clinical outcomes. Although not well-described in the setting of myositis, work from our animal model of HRS (histidyl-tRNA synthetase)-induced myositis suggests that anti-Ro60 antibodies may also be linked to specific MSAs such as anti-HRS/Jo-1.

Antibodies to Malondialdehyde-Acetaldehyde Adduct Are Associated With Prevalent and Incident Rheumatoid Arthritis-Associated Interstitial Lung Disease in US Veterans.

Objective: The objective of this study is to determine the associations of protein-specific anti-malondialdehyde-acetaldehyde (MAA) antibodies with prevalent and incident rheumatoid arthritis-interstitial lung disease (RA-ILD).

Methods: Within a multicenter, prospective cohort of US veterans with RA, RA-ILD was validated by medical record review of clinical diagnoses, chest imaging, and pathology. Serum antibodies to MAA-albumin, MAA-collagen, MAA-fibrinogen, and MAA-vimentin (IgA, IgM, and IgG) were measured by a standardized enzyme-linked immunosorbent assay.

Plasma Matrix Metalloproteinase Concentrations and Risk of Interstitial Lung Disease in a Prospective Rheumatoid Arthritis Cohort.

Objective: To evaluate the associations of plasma matrix metalloproteinases (MMPs) with prevalent and incident interstitial lung disease (ILD) in people with rheumatoid arthritis (RA).

Methods: Within a multicenter, prospective cohort of US veterans with RA, we performed a cross-sectional study of prevalent ILD and cohort study of incident ILD. ILD diagnoses were validated by medical record review of provider diagnoses and chest imaging and/or pathology reports.

Development and internal validation of a clinical and genetic risk score for rheumatoid arthritis-associated interstitial lung disease.

Objective: Although clinical and genetic risk factors have been identified for rheumatoid arthritis-associated interstitial lung disease (RA-ILD), there are no current tools allowing for risk stratification. We sought to develop and validate an ILD risk model in a large, multicentre, prospective RA cohort.

Methods: Participants in the Veterans Affairs RA (VARA) registry were genotyped for 12 single nucleotide polymorphisms (SNPs) associated with idiopathic pulmonary fibrosis.

Serum cytokine profiles of adults with idiopathic inflammatory myopathies.

Objectives: There is a paucity of available biomarkers of disease activity in idiopathic inflammatory myopathies (IIM), and serum cytokines/chemokines hold potential as candidate biomarkers. We aimed to determine serum cytokine profiles of IIM patients with active disease as compared to patients in remission and healthy controls.

Methods: The IIM patients with active disease (included patients enrolled in repository corticotropin injection trial), in remission, and healthy controls were enrolled in this cross-sectional observational study.

Correlation between B-cell epitope profile and clinical features of anti-MDA5 antibody-positive dermatomyositis.

Objectives: Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive (MDA5+) dermatomyositis patients exhibit a variety of clinical features. We therefore investigated whether patterns of B-cell epitope recognition are linked to the clinical course of MDA5+ dermatomyositis.

Methods: Our cross-sectional study used ELISA-based methods to determine the relationship between antibody recognition of overlapping 155 amino acid MDA5 subfragments and clinical features of 24 MDA5+ myositis patients.

Antigen-driven T cell-macrophage interactions mediate the interface between innate and adaptive immunity in histidyl-tRNA synthetase-induced myositis.

Introduction: Previous work in humans has demonstrated that both innate and adaptive immune signaling pathways contribute to the pathogenesis of idiopathic inflammatory myopathy (IIM), a systemic autoimmune disease targeting muscle as well as extra-muscular organs. To better define interactive signaling networks in IIM, we characterized the cellular phenotype and transcriptomic profiles of muscle-infiltrating cells in our established murine model of histidyl-tRNA synthetase (HRS)-induced myositis.

Methods: Myositis was induced in wild type (WT) and various congenic/mutant strains of C57BL/6 mice through intramuscular immunization with recombinant HRS.

Peripheral Blood Biomarkers for Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Systematic Review.

Background: Biomarkers have been proposed as tools to aid in the identification and prognostication of interstitial lung disease (ILD) in rheumatoid arthritis (RA). We performed a systematic review of studies evaluating peripheral blood biomarkers and their association with RA-ILD and its prognosis.

Methods: Medline, Embase, the Cochrane Library, and Scopus were queried for relevant studies, with the final search update on July 12, 2021.

Biomarkers of interstitial lung disease associated with primary Sjögren's syndrome.

Objectives: The aim of this study was to investigate serum biomarkers linked to primary Sjögren's syndrome (pSS)-associated interstitial lung disease (ILD).

Methods: 69 pSS patients were consecutively enrolled and evaluated via quantitative ILD scoring based on high-resolution computed tomography (HRCT). Biomarkers of interest were assessed by multiplex enzyme-linked immunosorbent assays (ELISAs).

Genetic, social, and environmental risk factors in rheumatoid arthritis-associated interstitial lung disease.

Objective: MUC5B and TOLLIP single nucleotide polymorphisms (SNPs) and cigarette smoking were associated with rheumatoid arthritis-interstitial lung disease (RA-ILD) in a predominantly Northern European population. We evaluated whether RA-ILD is associated with these genetic variants and HLA-DRB1 shared epitope (SE) alleles in a large RA cohort stratified by race and smoking history.

Methods: HLA-DRB1 SE alleles and MUC5B rs35705950 and TOLLIP rs5743890 SNPs were genotyped in U.

Increased susceptibility to organic dust exposure-induced inflammatory lung disease with enhanced rheumatoid arthritis-associated autoantigen expression in HLA-DR4 transgenic mice.

Immunogenetic as well as environmental and occupational exposures have been linked to the development of rheumatoid arthritis (RA), RA-associated lung disease, and other primary lung disorders. Importantly, various inhalants can trigger post-translational protein modifications, resulting in lung autoantigen expression capable of stimulating pro-inflammatory and/or pro-fibrotic immune responses. To further elucidate gene-environment interactions contributing to pathologic lung inflammation, we exploited an established model of organic dust extract (ODE) exposure with and without collagen-induced arthritis (CIA) in C57BL/6 wild type (WT) versus HLA-DR4 transgenic mice.

Predictors of long-term prognosis in rheumatoid arthritis-related interstitial lung disease.

The aim of the study was to identify specific clinical and serum protein biomarkers that are associated with longitudinal outcome of RA-associated interstitial lung disease (RA-ILD). 60 RA patients with clinical and serological profiles were assessed by HRCT and pulmonary function tests (PFTs) at baseline (Year 0) and 5 years post enrollment (Year 5). Progression versus non-progression was defined based on changes in Quantitative Modified HRCT scores and PFTs over time.

The impact of disease severity measures on survival in U.S. veterans with rheumatoid arthritis-associated interstitial lung disease.

Objectives: To determine whether RA and interstitial lung disease (ILD) severity measures are associated with survival in patients with RA-ILD.

Methods: We studied US veterans with RA-ILD participating in a multicentre, prospective RA cohort study. RA disease activity (28-joint DAS [DAS28-ESR]) and functional status (multidimensional HAQ [MDHAQ]) were collected longitudinally while pulmonary function tests (forced vital capacity [FVC], diffusing capacity for carbon monoxide) were obtained from medical records.

Role of Intravenous Immunoglobulin in Necrotizing Autoimmune Myopathy.

Background/objective: Immune-mediated necrotizing myopathy (IMNM) is a subtype of myositis that is associated with a refractory phenotype and poorer prognosis. The aim of the study was to provide single large center experience of outcomes of intravenous immunoglobulin (IVIg) for patients with IMNM using longitudinally collected data.

Methods: This case series longitudinally evaluated 4 of the 6 myositis core set measures at baseline and at 3 and 6 months after IVIg on 20 adult IMNM patients from 2014 to 2019 at the University of Pittsburgh.

The impact of airborne endotoxin exposure on rheumatoid arthritis-related joint damage, autoantigen expression, autoimmunity, and lung disease.

Airborne biohazards are risk factors in the development and severity of rheumatoid arthritis (RA) and RA-associated lung disease, yet the mechanisms explaining this relationship remain unclear. Lipopolysaccharide (LPS, endotoxin) is a ubiquitous inflammatory agent in numerous environmental and occupational air pollutant settings recognized to induce airway inflammation. Combining repetitive LPS inhalation exposures with the collagen induced arthritis (CIA) model, DBA1/J mice were assigned to either: sham (saline injection/saline inhalation), CIA (CIA/saline), LPS (saline/LPS 100 ng inhalation), or CIA + LPS for 5 weeks.

Granulomatous Myositis Associated With Acetylcholine Receptor Antibodies Without Clinical Myasthenia.

Myasthenia gravis associated with concurrent inflammatory myopathy is a rare but well-described syndrome, most often seen in patients with thymoma. We present a case of biopsy-proven granulomatous myositis associated with positive acetylcholine receptor binding, blocking, and modulating and antistriated antibodies, without clear clinical symptoms of myasthenia gravis and in the absence of thymoma. In addition, we include rarely reported neuromuscular ultrasound findings of granulomatous myositis in a patient without sarcoidosis.

Association of Agricultural, Occupational, and Military Inhalants With Autoantibodies and Disease Features in US Veterans With Rheumatoid Arthritis.

Objective: To determine the association of inhalant exposures with rheumatoid arthritis (RA)-related autoantibodies and severity in US veterans.

Methods: Participants in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were mailed surveys assessing occupational, agricultural, and military inhalant exposures. Demographic characteristics, disease activity, functional status, and extraarticular features were obtained from the VARA registry, while HLA-DRB1 shared epitope (SE) status, anti-cyclic citrullinated peptide (anti-CCP) antibodies, and rheumatoid factor (RF) were measured using banked DNA/serum from enrollment.

Risk Factors and Cancer Screening in Myositis.

The idiopathic inflammatory myopathies, particularly dermatomyositis, are associated with an increased risk of cancer. Lung, ovarian, breast, colon, prostate, and cervical cancers, and hematologic malignancies, are among the most common associated cancers. Risk stratification for cancer in patients with myositis is based on clinical risk factors/red flags, myositis clinical subtypes, and myositis-specific autoantibodies.

Comparative Profiling of Serum Protein Biomarkers in Rheumatoid Arthritis-Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis.

Objective: Interstitial lung disease (ILD) is a frequent complication of rheumatoid arthritis (RA), occurring in up to 40% of patients during the course of their disease. Early diagnosis is critical, particularly given the shared clinicoepidemiologic features between advanced rheumatoid arthritis-associated ILD (RA-ILD) and idiopathic pulmonary fibrosis (IPF). This study was undertaken to define the molecular basis of this overlap through comparative profiling of serum proteins in RA-ILD and IPF.