Sjogren's syndrome: Review of the aetiology, Pathophysiology & Potential therapeutic interventions.

Jj Nair,Tp Singh

doi:10.4317/jced.53605

Abstract

BackgroundSjogren’s syndrome (SS) is an autoimmune disorder characterised by lymphocytic infiltration of exocrine glands, resulting in glandular dysfunction. Objectives: This study aims to review the aetiology of Sjogren’s syndrome, highlight aspects that contribute to the pathophysiology of the disease and explore treatment options that target different mediators of pathogenesis.Material and MethodsThe MEDLINE/PubMed and Google Scholar databases were searched systematically with the terms “Sjogren’s syndrome”; “clinical”; “treatment”; “management”. Eligible studies had to meet a predefined inclusion criteria.Results912 identified studies were evaluated against the inclusion criteria. 25 eligible studies were included for review. Sjogren’s syndrome is a multifactorial condition with genetic, environmental and hormonal factors playing a role in establishing the condition. B-cell activating factor (BAFF) is an important mediator in the induction and perpetuation of this condition. Elevated BAFF levels, found in patients with SS, promote growth of B-cells and subsequent production of autoantibody; anti-SSA/Ro. BAFF inhibitors are important potential therapeutic drugs that may be effective in patients with Sjogren’s syndrome. Other potential targets include CD20 and CD22 that cause B-cell depletion.ConclusionsThe pathophysiology of this exocrinopathy has not fully been elucidated. Potential therapeutic interventions include BAFF inhibitors and anti-CD20 and anti-CD22 therapy. However, no clinical trials have been conducted on subjects with Sjogren’s syndrome to support existing research. Key words:Sjogren’s syndrome, autoimmune, rheumatology.

Highlights

Sjogren’s syndrome (SS) is an autoimmune disorder caused by the lymphocytic infiltration of exocrine glands resulting in glandular dysfunction, preferentially of the salivary and lacrimal glands [1]
This study aims to review the aetiology of Sjogren’s syndrome, highlight aspects that contribute to the pathophysiology of the disease and explore treatment options that target different mediators of pathogenesis
Belimumab is a human monoclonal antibody against BAFF that inhibits it’s activity, subsequent B-cell development, and autoantibody production. The efficacy of this drug has been trialled on patients with systemic lupus erythematosus (SLE), another autoimmune disorder with B-cells playing a prominent role in the pathogenesis [37]

Summary

Introduction

Sjogren’s syndrome (SS) is an autoimmune disorder caused by the lymphocytic infiltration of exocrine glands resulting in glandular dysfunction, preferentially of the salivary and lacrimal glands [1]. This suggests its role in activating auto-reactive Bcells and modulating the level of autoantibody production [36] This has therapeutic implications in patients as anti-BAFF antibodies or BAFF antagonists may be used to treat Sjogren’s syndrome. Belimumab is a human monoclonal antibody against BAFF that inhibits it’s activity, subsequent B-cell development, and autoantibody production The efficacy of this drug has been trialled on patients with systemic lupus erythematosus (SLE), another autoimmune disorder with B-cells playing a prominent role in the pathogenesis [37]. In the presence of anti-Ro52 and in patients with Sjogren’s syndrome, ubiquitination of Ro52 is inhibited by the autoantibody This leads to increased production of pro-inflammatory cytokines regulated by IRF and contributes to the pathogenesis of SS [42]. Methotrexate has been shown to improve subjective symptoms of dry mouth and eyes, while there is no improvement in flow rates of lacrimal and salivary glands [45]

Discussion

Conclusions