ERdj5 Function Is Involved in Inflammatory Manifestations of Sjögren's Syndrome in the Salivary Glands

Eirini Apostolou¹, Petros Moustardas², Takao Iwawaki³, Giannis Spyrou² and Athanasios G. Tzioufas⁴, ¹Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece, ²Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine, Linköping University, Linköping, Sweden, ³Life Science, Division of Cell Medicine, Medical Research Institute, Kanazawa Medical University, Ishikawa, Japan, ⁴School of Medicine, Pathophysiology Department, National and Kapodistrian University of Athens, Athens, Greece

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Sjogren's syndrome

Session Information

Date: Sunday, November 13, 2016

Title: Sjögren's Syndrome - Poster I: Translational Science

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Sjögren’s syndrome is a chronic autoimmune disorder that affects mainly the exocrine glands. The initiation and causative agents are still unknown. Endoplasmic Reticulum (ER) stress proteins have been suggested to participate in autoimmune and inflammatory responses, either by acting as autoantigens themselves, or by modulating factors in inflammatory responses.ERdj5 is anER-resident chaperone proteinwith a disulfide reductase activityand is required for the translocationof misfolded proteins across the ERfor proteasomaldegradation. In this study we sought to investigate the role of ERdj5 in the salivary glands, in associationwith inflammation and autoimmunity.

Methods: In situexpression of ERdj5 was studied immunohistochemically in minor salivary gland tissues (MSG) from primarySjögren’s Syndrome (SS)-patients and non-SS sicca-complaining controls. Submaxillary glands and sera from both male and female ERdj5-knockoutmice andage-matched wild types were collected at 6,34 and 52 weeks of age. Tissue samples were analyzed microscopically, while sera were screened for anti-nuclear antibodies(ANAs).

Results: Human MSGs expressed ERdj5,with higher stain intensity in MSGs of SS patients with severe inflammatory lesions.Mice deficient in ERdj5 spontaneously developed SS-like inflammation in submaxillary glands and ANAssystemically. Inflammation was characterized by T and B infiltrating lymphocytes. Notably, female ERdj5-knockout mice developed severe chronic periductal inflammation in contrast to the much milder phenotype found in male littermates.

Conclusion: Salivary glands of ERdj5-knockout mice resemble the pathologic lesions of human Sjögren’s syndrome whereasERdj5 wasinduced in MSGs of SS patients. Our findings suggest a critical connection betweenthe function of the ER stress chaperone protein ERdj5 andautoimmune inflammatory responses in the salivary glands.

Disclosure: E. Apostolou, None; P. Moustardas, None; T. Iwawaki, None; G. Spyrou, None; A. G. Tzioufas, None.

To cite this abstract in AMA style:

Apostolou E, Moustardas P, Iwawaki T, Spyrou G, Tzioufas AG. ERdj5 Function Is Involved in Inflammatory Manifestations of Sjögren’s Syndrome in the Salivary Glands [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/erdj5-function-is-involved-in-inflammatory-manifestations-of-sjogrens-syndrome-in-the-salivary-glands/. Accessed .

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