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Sjogren’s syndrome: Pathogenesis

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SJOGREN’S SYNDROME: INTRODUCTION AND PATHOGENESIS

Author: Sanketh DS, MDS

INTRODUCTION

Sjogren’s syndrome (SS) is an autoimmune, chronic inflammatory disease characterized by dense infiltration of lymphocytes in the exocrine glands. Essentially, the body’s own immune cells, the lymphocytes, attack and infiltrate various exocrine glands and cause their functional impairment. The salivary and lacrimal glands are classically affected in SS, resulting in xerostomia (dry mouth) and keratoconjuctivitis sicca (dry eyes) respectively.  Exocrine glands in the gastrointestinal system, respiratory system, skin and vagina may also be affected.

There are two types of presentations of SS. One where patients manifest with functional impairment of the exocrine glands especially with xerostomia and keratoconjuctivitis sicca and the other where patients apart from dry mouth and dry eyes also have other associated autoimmune diseases like rheumatoid arthritis, systemic lupus erythematosus or scleroderma. The former is called Primary SS or Sicca syndrome and the latter is called Secondary SS.

PATHOGENESIS

Though the exact cause or etiology of the disease is not known, it is established that SS is an autoimmune disease where the body’s immune cells fail to distinguish between ‘foreign’ and ‘self’ molecules or antigens. They recognize the body’s own cells as foreign and destroy them. There are primarily two factors, genetic and environmental, which may drive this process.

Patients with SS are known to be genetically susceptible to this disease. It has been reported that many patients with SS have a family history of the same and even other autoimmune diseases. These patients have expression of certain MHC genes which make them susceptible. These are genes which code for molecules called Human Leukocyte Antigens and some of them implicated in this disease are HLA DR52, HLA DR3, HLA-B8 and HLA-DQ2.  

Environmental factors like viral infections are known to trigger events in the susceptible individual which may instigate the autoimmune attack. Viruses may cause cell damage and apoptosis of glandular tissue, exposing antigens which are recognized by self-reactive lymphocytes/T-cells. Another theory hypothesized is that viruses may induce the disease by what is called molecular mimicry. These viruses may have similar structure and amino acid sequences of self-antigens, causing lymphocytes to cross-react and attack self-antigens. Epstein-Barr virus, human T-cell lymphotropic virus, Cytomegalo virus and Hepatitis C virus among others have been implicated in causing the disease. Main self-antigens implicated are ribonucleoproteins SS-A and SS-B and cell membrane cytoskeletal proteins like alpha-fodrin.

After a viral attack antigen presenting cells (APCs) like dendritic cells in the gland recognize and pick up self-antigens. T-cells migrating to the gland recognize the self-antigens presented by the APCs and produce pro-inflammatory cytokines, propagating recruitment of more T-cells and perpetuating inflammation. Apart from cytokines produced by T-cells, APCs produce cytokines called B-cell activating factor (BAFF) that activate B-cells to produce anti nuclear antibodies like anti SS-A anti SS-B. Anti SS-A antibodies are found in approximately 50-76% of patients and anti-SS-B antibodies have been found in 30-60% of patients. This way, T-cells and B-cells are self-perpetuating, chronically infiltrating glands causing sufficient damage and functional impairment.  

REFERENCES

Bayetto K, Logan RM. Sjögren’s syndrome: a review of aetiology, pathogenesis, diagnosis and management. Aust Dent J. 2010 Jun;55 Suppl 1:39-47.

Ramos-Casals M, Font J. Primary Sjögren’s syndrome: current and emergent aetiopathogenic concepts. Rheumatology (Oxford). 2005 Nov;44(11):1354-67.

Al-Hashimi I. Sjögren’s syndrome: diagnosis and management. Women’s Health (2007) 3(1), 107–122.

Sjogren’s syndrome (Medscape). Available at: https://emedicine.medscape.com/article/332125-overview

Neville BW, Damm DD, Allen CM, Chi A. Oral and Maxillofacial Pathology. South Asian ed. Elsevier; 2016.

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