Role of Jo-1 in the Immunopathogenesis of the Anti-synthetase Syndrome

Ascherman, Dana P.

doi:10.1007/s11926-015-0532-1

Cited by 30 publications

(30 citation statements)

References 34 publications

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“…This disease is a heterogeneous group of autoimmune disease characterized by interstitial lung disease (ILD), myositis, mechanic's hands, Raynaud's phenomenon, and arthritis 61 . Up to now, there are mainly eight anti-ARS autoantibodies including anti-histidyl (anti-Jo-1), anti-alanyl (anti-PL-12), anti-threonyl (anti-PL-7), anti-asparaginyl (anti-KS), anti-glycyl (anti-EJ), anti-phenylalanyl (anti-Zo), anti-tyrosyl (anti-Ha), and anti-isoleucyl (anti-OJ) in ASSD 62,63 . Among them, anti-Jo-1 antibody is the most common.…”

Section: Arss and Autoimmune Diseasesmentioning

confidence: 99%

Roles of aminoacyl-tRNA synthetases in immune regulation and immune diseases

Nie

Sun

et al. 2019

Cell Death Dis

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Aminoacyl-tRNA synthetases (ARSs) play a vital role in protein synthesis by linking amino acids to their cognate transfer RNAs (tRNAs). This typical function has been well recognized over the past few decades. However, accumulating evidence reveals that ARSs are involved in a wide range of physiological and pathological processes apart from translation. Strikingly, certain ARSs are closely related to different types of immune responses. In this review, we address the infection and immune responses induced by pathogen ARSs, as well as the potential anti-infective compounds that target pathogen ARSs. Meanwhile, we describe the functional mechanisms of ARSs in the development of immune cells. In addition, we focus on the roles of ARSs in certain immune diseases, such as autoimmune diseases, infectious diseases, and tumor immunity. Although our knowledge of ARSs in the immunological context is still in its infancy, research in this field may provide new ideas for the treatment of immune-related diseases.

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Section: Arss and Autoimmune Diseasesmentioning

confidence: 99%

Roles of aminoacyl-tRNA synthetases in immune regulation and immune diseases

Nie

Sun

et al. 2019

Cell Death Dis

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“…In our case, the sequence of the first 60 amino acids of HisRS (UniProtKB identifier P12081) was examined to predict peptides that can bind DRB1*03:01; residues 11-23 (HisRS 11-23 ) contained 2 such motifs and therefore had a high probability of containing a bona fide DRB1*03:01 epitope. Thus, HisRS [11][12][13][14][15][16][17][18][19][20][21][22][23] peptide was selected for further functional assays ( Figure 1A). Immunohistochemistry and histopathology.…”

Section: Identification Of the Hisrs T Cell Epitopementioning

confidence: 99%

Proinflammatory Histidyl–Transfer RNA Synthetase–Specific CD4+ T Cells in the Blood and Lungs of Patients With Idiopathic Inflammatory Myopathies

Galindo-Feria

Albrecht

Fernandes‐Cerqueira

et al. 2019

Arthritis & Rheumatology

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Objective Autoantibodies targeting histidyl–transfer RNA synthetase (HisRS; anti–Jo‐1) are common in the idiopathic inflammatory myopathies (IIMs) and antisynthetase syndrome. This study was undertaken to investigate immunity against HisRS in the blood and lungs of patients with IIM/antisynthetase syndrome. Methods Bronchoalveolar lavage (BAL) fluid, BAL fluid cells, and peripheral blood mononuclear cells (PBMCs) from patients with IIM/antisynthetase syndrome (n = 24) were stimulated with full‐length HisRS protein or a HisRS‐derived peptide (HisRS11–23). BAL fluid and PBMCs from patients with sarcoidosis (n = 7) and healthy subjects (n = 12) were included as controls. The CD4+ T cell response was determined according to levels of CD40L up‐regulation and cytokine expression using flow cytometry. Anti–Jo‐1 autoantibody responses in the serum and BAL fluid were assessed by enzyme‐linked immunosorbent assay. Lung biopsy samples from patients with IIM/antisynthetase syndrome (n = 14) were investigated by immunohistochemistry. Results In BAL fluid, CD4+ T cells from 3 of 4 patients with IIM/antisynthetase syndrome responded to stimulation with HisRS protein, as measured by the median fold change in CD40L expresssion in stimulated cells compared to unstimulated cells (median fold change 3.6, interquartile range [IQR] 2.7–14.7), and 2 of 3 patients with IIM/antisynthetase syndrome had the highest responses to HisRS11–23 (median fold change 88, IQR 27–149). In PBMCs, CD4+ T cells from 14 of 18 patients with IIM/antisynthetase syndrome responded to HisRS protein (median fold change 7.38, IQR 2.69–31.86; P < 0.001), whereas a HisRS11–23 response was present in 11 of 14 patients with IIM/antisynthetase syndrome (median fold change 3.4, IQR 1.87–10.9; P < 0.001). In the control group, there was a HisRS11–23 response in 3 of 7 patients with sarcoidosis (median fold change 2.09, IQR 1.45–3.29) and in 5 of 12 healthy controls (median fold change 2, IQR 1.89–2.42). CD4+ T cells from patients with IIM/antisynthetase syndrome displayed a pronounced Th1 phenotype in the BAL fluid when compared to the PBMCs (P < 0.001), producing high amounts of interferon‐γ and interleukin‐2 following stimulation. Anti–Jo‐1 autoantibodies were detected in BAL fluid and germinal center (GC)–like structures were seen in the lung biopsy samples from patients with IIM/antisynthetase syndrome. Conclusion The results of this study demonstrate a pronounced presence of HisRS‐reactive CD4+ T cells in PBMCs and BAL fluid cells from patients with IIM/antisynthetase syndrome as compared to patients with sarcoidosis and healthy controls. These findings, combined with the presence of anti–Jo‐1 autoantibodies in BAL fluid and GC‐like structures in the lungs, suggest that immune activation against HisRS might take place within the lungs of patients with IIM/antisynthetase syndrome.

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“…In 1999, Wakasugi and Schimmel identified that these synthetases may act as cytokines, assisting in cell death and recruitment of inflammatory cells (22). Further studies, summarized by Ascherman in 2015, have identified innate and adaptive immunity in the pathogenesis of anti-synthetase syndrome (23). …”

Section: Diagnosismentioning

confidence: 99%

The Diagnosis and Treatment of Antisynthetase Syndrome

Witt

Curran

Strek

2016

Clinical Pulmonary Medicine

178

164

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Anti-synthetase syndrome is an autoimmune condition, characterized by antibodies directed against an aminoacycl transfer RNA synthetase along with clinical features that can include interstitial lung disease, myositis, Raynaud’s phenomenon, and arthritis. There is a higher prevalence and increased severity of interstitial lung disease in patients with anti-synthetase syndrome, as compared to dermatomyositis and polymyositis, inflammatory myopathies with which it may overlap phenotypically. Diagnosis is made by a multidisciplinary approach, synthesizing rheumatology and pulmonary evaluations, along with serologic, radiographic, and occasionally muscle and/or lung biopsy results. Patients with anti-synthetase syndrome often require multi-modality immunosuppressive therapy in order to control the muscle and/or pulmonary manifestations of their disease. The long-term care of these patients mandates careful attention to the adverse effects and complications of chronic immunosuppressive therapy, as well as disease-related sequelae that can include progressive interstitial lung disease necessitating lung transplantation, pulmonary hypertension, malignancy and decreased survival. It is hoped that greater awareness of the clinical features of this syndrome will allow for earlier diagnosis and appropriate treatment to improve outcomes in patients with anti-synthetase syndrome.

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Role of Jo-1 in the Immunopathogenesis of the Anti-synthetase Syndrome

Cited by 30 publications

References 34 publications

Roles of aminoacyl-tRNA synthetases in immune regulation and immune diseases

Roles of aminoacyl-tRNA synthetases in immune regulation and immune diseases

Proinflammatory Histidyl–Transfer RNA Synthetase–Specific CD4+ T Cells in the Blood and Lungs of Patients With Idiopathic Inflammatory Myopathies

The Diagnosis and Treatment of Antisynthetase Syndrome

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