Associations of MHC Class II Alleles in Norwegian Primary Sjögren's Syndrome Patients: Implications for Development of Autoantibodies to the Ro52 Autoantigen

Abstract

Sjo Ègren's syndrome (SS) is a chronic autoimmune disease characterized by dryness of the eyes and mouth. Currently, the highly polymorphic major histocompatibility complex (MHC) genes are the best documented genetic risk factor for the development of autoimmune disease. We examined the MHC class II alleles DRB1, DRB3, DRB4, DRB5, DQA1 and DQB1 in a group of Norwegian pSS patients and compared with a group of healthy controls. Because a number of studies have shown that some of the MHC class II alleles are not associated with the disease as a whole, but rather to the development of autoantibodies, anti-Ro52 autoantibodies in serum were measured and compared to MHC class II allele status. A clear association with pSS was detected for the DRB1*0301 and DRB3*0101 alleles, but these alleles were more closely associated with the presence of anti-Ro52 autoantibodies than with pSS itself. Moreover, the DQA1*0501 and DQB1*0201 alleles were only associated with the presence of anti-Ro52 autoantibodies.

The genetics of primary Sjögren’s syndrome

“…Moreover, these alleles were more closely associated with the production of anti-Ro52 kD antibodies than with the disease itself [20]. The association with HLA-DRB1*15 was also seen in patients with secondary SS.…”

“…Furthermore, this subgroup was associated with lower levels of circulating Vδ1-positive T cell receptor γ/ δ (TCR γ/δ) cells and higher levels of circulating CD45 Ropositive TCR γ/δ cells [26]. More recently, a Norwegian study revealed an association with HLA DQA1*0501 and DQB1*0201 with the presence of anti-Ro52 kD in patients with primary SS [20]. Overall, the most consistent HLA-DQ effect observed is an association of DQB1*0201 and DQA1*0501 with the presence of anti-Ro.…”

Gene expression and chromosomal location for susceptibility to Sjögren's syndrome

“…Table 1 shows the mean ratio values of the 20 top ranked genes. Ten of these 20 have been previously associated with SS [5,9,11,[21][22][23][24][25][26][27], whereas ten (IGHG1, RARRES1, NCF1, SYT1, HLA-DMA, PCOLN3, COL3A1, PRG1, COTL1, BF) are described here for the first time associated to primary SS. This new gene set included all top ranked down-regulated genes.…”

Recent advances in understanding molecular mechanisms in the pathogenesis and antibody profile of Sjögren’s syndrome

“…The production and persistence of autoantibodies in autoimmune conditions occurs because of immune dysregulation with a resultant break in tolerance, regardless of whether these autoantibodies are pathogenic or not [26]. Despite extensive work on the characterization of autoantigens, the cellular basis of autoantibody production, and the association of certain autoantibodies with particular major histocompatibility complex class II alleles [27], little is known about the usage of immunoglobulin (Ig) V genes in autoimmune conditions and the respective autoantibodies. The increased knowledge about tissue B cell immunology [28] and the role of cytokines and chemokines has already been alluded to.…”