Genetic predisposition
The genetic locus most significantly associated with primary SS is the major histocompatibility complex/human leukocyte antigen (MHC/HLA) region, as demonstrated by the preliminary results of the first genome-wide association study. This study included data from a discovery cohort of 395 patients of European ancestry with primary Sjögrens syndrome, and 1,975 healthy control individuals, and from a replication study that comprised 1,234 cases and 4,779 healthy controls. Associations with polymorphisms located at six independent loci were also detected; IRF5, STAT4, BLK, IL12A, TNIP1, and CXCR5. This also suggested the activation of the innate immune system, notably through the IFN system, B-cell activation through CXCR5-directed recruitment to lymphoid follicles and B-cell receptor (BCR) activation involving BLK, and T-cell activation owing to HLA susceptibility and the IL-12-IFN-γ-axis.Patients of different ethnic origin carry different HLA-susceptibility alleles, of which HLA-DR and HLA-DQ are involved in the pathogenesis of Sjögrens syndrome. For example, patients from Northern and Western Europe and from North America show a high prevalence of B8, DRw52, and DR3 genes. HLA class II alleles are associated with the presence of specific subsets of autoantibodies, rather than with the disease itself. Autoantibodies refer to the loss of B-cell tolerance leading to production of antibodies directed against diverse organ-specific and organ nonspecific antigens. Association between HLA and SS is restricted to patients with anti-SSA/Ro or anti-SSB/La antibodies.
Sjögren introduced the term keratoconjunctivitis sicca for the symptom of dry eyes (keratoconjunctivitis). In 1933, he published his doctoral thesis describing 19 females, most of whom were postmenopausal and had arthritis, showing clinical and pathological manifestations of the syndrome. Sjögren clarified that keratoconjunctivitis sicca, resulting from water deficiency, had no relation to xerophthalmia, resulting from vitamin A deficiency. Sjögrens thesis was not well received as the Board of Examiners criticized some clinical aspects.After extensive research and data collection, Sjögren published an essential paper in 1951, describing 80 patients with keratoconjunctivitis sicca, 50 of whom also had arthritis. His subsequent follow-up conference trips pertaining to his paper led to an international interest in Sjögrens syndrome. The term "keratoconjunctivitis sicca" was coined by Sjögren himself and began to be identified as Sjögrens syndrome in literature, although it can now have more general usage. Research
Research into multifactorial autoimmune diseases such as SS focuses on expanding the knowledge surrounding the disorder, improving diagnostic tools and finding ways to prevent, manage and cure the disorder. The United Kingdom Primary Sjögrens Syndrome Registry, a tissue biobank of samples taken for research, supported by the Medical Research Council, UK, was established in 2010. It supports clinical trials and genetic studies of Sjögrens syndrome and is open to those wishing to participate in research studies and to researchers studying the disease.As with other autoimmune diseases, susceptibility to Sjögrens syndrome is greatly influenced by the human leukocyte antigen.