Sjogren’s Syndrome

There is much to suggest that Sjögren’s syndrome (SS) is, like many connective tissue diseases, an autoimmune disorder. Support for this hypothesis includes a female preponderance, distinctive HLA associations, familial clustering with other autoimmune processes, the presence of autoantibodies, and the existence of shared clinical features (arthritis, Raynaud phenomenon, serositis) with other autoimmune connective tissue diseases.

The close relationship of primary SS and systemic lupus erythematosus (SLE) has led to the suggestion that primary SS likely shares common pathogenetic features with SLE [1]. If it is considered that SLE consists of several subgroups that are each characterized by particular autoantibodies and HLA-DR alleles, then SS has close similarities to one of these SLE subsets (ie, HLA-DR3, anti-SS A antibody positive). In this regard, SS might be loosely considered a subset of SLE, characterized by particular homing receptors that allow lymphocytic infiltrates into particular extranodal sites, such as salivary and lacrimal glands. Thus, the features of SS include ocular and oral dryness, as well as increased frequency of lymphoproliferative disorders including an elevated risk of lymphoma [1].

Due to the relative ease and safety of biopsying the target organ of inflammation (eg, the salivary or lacrimal gland, or conjunctiva), SS provides a prototype for understanding the interaction of immune and neuro-endocrine systems. With availability of techniques of molecular biology to analyze the plethora of proteins (proteomics) of small tissue samples and fluids, it should be possible to correlate the changes in tissue with those in blood and draining fluids (ie, tears and saliva) in order to assess prognosis and to provide biomarkers for response to therapy.

Studies have suggested an important role for B-cells and type I interferon [2-6], in contrast to the pivotal role of TNF in RA patients [7-9]. These observations will drive the next stage of therapeutic trials in SS.

Although features of dry eyes, dry mouth and systemic manifestations such as vasculitis remain well understood, the vague symptoms of muscle pain, mild cognitive defects and fatigue (fibromyalgia-like) remain poorly characterized at a molecular level, and treatment for these common symptoms will depend on further understanding of pathogenesis.