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Sex differential association of dermatomyositis with Sjogren syndrome.

ABSTRACT: Although dermatomyositis and Sjögren syndrome share serologic autoantibodies and genetic polymorphisms, population data about the incidence of Sjögren syndrome in patients with dermatomyositis is unavailable. We performed a nationwide cohort study to explore the potential relation between dermatomyositis and Sjögren syndrome and, if an association exists, to elucidate whether it varies by sex.We identified all patients with newly diagnosed dermatomyositis from the Registry of Catastrophic Illness Database in Taiwan between Jan. 1, 1998, and Dec. 31, 2011. Each patient was matched to, at most, 5 control patients from the National Health Insurance Research Database by age, sex and entry date. Cox regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) of Sjögren syndrome after adjusting for age, sex, rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis.A total of 1602 patients with dermatomyositis and 7981 control patients were enrolled in the study. There was a positive association of having Sjögren syndrome among patients with dermatomyositis after adjusting for age, sex, rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis (HR 2.67, 95% CI 2.01-3.54). The association was more pronounced in the male cohort (HR 2.69, 95% CI 1.19-6.09).We found a sex differential association of Sjögren syndrome among patients with dermatomyositis independent of age and concomitant autoimmune disease. Further studies are required to determine the clinical importance of this association for both outcomes and therapeutic options.

SUBMITTER: Tseng CC

PROVIDER: S-EPMC5289869 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Sex differential association of dermatomyositis with Sjögren syndrome.

Tseng Chia-Chun CC Chang Shun-Jen SJ Tsai Wen-Chan WC Ou Tsan-Teng TT Wu Cheng-Chin CC Sung Wan-Yu WY Hsieh Ming-Chia MC Yen Jeng-Hsien JH

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 20170201 5

<h4>Background</h4>Although dermatomyositis and Sjögren syndrome share serologic autoantibodies and genetic polymorphisms, population data about the incidence of Sjögren syndrome in patients with dermatomyositis is unavailable. We performed a nationwide cohort study to explore the potential relation between dermatomyositis and Sjögren syndrome and, if an association exists, to elucidate whether it varies by sex.<h4>Methods</h4>We identified all patients with newly diagnosed dermatomyositis from ...[more]

PMID: 28246264

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Project description:ObjectivePrimary Sjögren syndrome (pSS) is characterized by T and B cell infiltration of exocrine glands. The cysteine protease cathepsin S (CatS) is crucially involved in MHCII processing and T cell stimulation, and elevated levels have been found in patients with RA, psoriasis and pSS. However, little is known about the functional characteristics and mechanisms of SS-A- and SS-B-specific T cells in pSS patients. We herein investigated the inhibition of CatS activity in different biocompartments of pSS patients including antigen-specific T cell responses.MethodsEx vivo CatS activity was assessed in tears, plasma and saliva of 15 pSS patients and 13 healthy controls (HC) and in the presence or absence of the specific CatS inhibitor RO5459072. In addition, antigen (SS-A (60kD), SS-B, influenza H3N2, tetanus toxoid and SEB)-specific T cell responses were examined using ex vivo IFN-?/IL-17 Dual ELISPOT and Bromdesoxyuridin (BrdU) proliferation assays in the presence or absence of RO5459072. Supernatants were analysed for IL-1?, IL-6, IL-10, TNF-?, IL-21, IL-22 and IL-23, using conventional ELISA.ResultsCatS activity was significantly elevated in tear fluid, but not other biocompartments, was inversely associated with exocrinic function in pSS patients and could significantly be suppressed by RO5459072. Moreover, CatS inhibition by RO5459072 led to strong and dose-dependent suppression of SS-A/SS-B-specific T cell effector functions and cytokine secretion by CD14+ monocytes. However, RO5459072 was incapable of suppressing SS-A/SS-B-induced secretion of cytokines in CD14+ monocytes when T cells were absent, confirming a CatS/MHCII-mediated mechanism of suppression.ConclusionCatS activity in tear fluid seems to be a relevant biomarker for pSS disease activity. Conversely, CatS inhibition diminishes T cell and associated monokine responses towards relevant autoantigens in pSS. Thus, CatS inhibition may represent a promising novel treatment strategy in pSS.

Project description:Primary Sjögren's syndrome (pSS) is a heterogeneous disease characterised by a wide spectrum of manifestations that vary according to the different stages of the disease and among different subsets of patients. The aim of this qualitative literature review is to summarise the recent advances that have been reported in pSS, ranging from the early phases to the established disease and its complications. We analysed the diagnostic, prognostic, and management aspects of pSS, with a look into future clinical and research developments. The early phases of pSS, usually antedating diagnosis, allow us to investigate the pathophysiology and risk factors of the overt disease, thus allowing better and timely patient stratification. Salivary gland ultrasound (SGUS) is emerging as a valid complementary, or even alternative, tool for histopathology in the diagnosis of pSS, due to a standardised scoring system with good agreement and performance. Other promising innovations include the application of artificial intelligence to SGUS, ultrasound-guided core needle biopsy, and a wide array of novel diagnostic and prognostic biomarkers. Stratifying pSS patients through the integration of clinical, laboratory, imaging, and histopathological data; differentiating between activity-related and damage-related manifestations; and identifying patients at higher risk of lymphoma development are essential steps for an optimal management and individualised treatment approach. As new treatment options are emerging for both glandular and systemic manifestations, there is a need for a more reliable treatment response evaluation. pSS is a complex and heterogeneous disease, and many distinct aspects should be considered in the different stages of the disease and subsets of patients. In recent years, efforts have been made to improve our understanding of the disease, and certainly in the coming years, some of these novelties will become part of our routine clinical practice, thus improving the management of pSS patients.

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Sex differential association of dermatomyositis with Sjogren syndrome.

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Sex differential association of dermatomyositis with Sjögren syndrome.

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