To assess salivary gland tissues obtained from patients with primary Sjögren's syndrome (SS) for the gene expression profile of the candidate genes TNFRSF6 (Fas), TNFSF6 (FasL), SSA1 (Ro52 alpha and the splice variant Ro52 beta), SSB (La), CTLA4, PDCD1 (PD-1), and ORM2, which were selected on the basis of their putative participation in salivary gland inflammation.
In addition to LSGB pattern, anti-SSA/Ro52-positivity, reduced C3 levels, hypoalbuminemia and anemia, also indicate significant association with renal involvement in pSS.
Primary Sjögren's syndrome is associated with a markedly increased risk of cardiovascular disease and the presence of Ro/SSA and La/SSB autoantibodies identify the subgroup of patients carrying the highest risk.
Mononuclear cell infiltration of exocrine glands, production of Ro/SSA and La/SSB autoantibodies, along with oral and ocular dryness, are characteristic features of primary Sjögren's syndrome (pSS).
The increased Ro/SSA 60 and La/SSB mRNA expression in MSG of patients with pSS as well as the differential Ro/SSA 60 and La/SSB protein expression in ductal cells of MSG in patients with pSS suggest that these these 2 autoantigens, but not Ro/SSA 52, are probably involved in triggering and maintaining the tissue-specific autoimmune response in pSS MSG and may contribute to the antigen-driven immune response and local autoantibody production in pSS.
RNA from purified CD19+ B cells from 12 anti-SSA antibody-positive untreated female patients with pSS and 20 healthy blood donors was subjected to whole transcriptome sequencing.
Remarkably, anti-Ro52 autoantibodies from patients with primary Sjögren's syndrome, systemic lupus erythematosus, systemic sclerosis or polymyositis were restricted to two IgG1 kappa clonotypes that migrated as a single species on isoelectric focusing; shared a common light chain paired with one of two closely-related heavy chains; and were public in unrelated patients.
The susceptibility to pSS and/or the presence of SS-A/SS-B autoantibodies in pSS patients is associated with DRB1*03-DQB1*02 and DRB1*02-DQB1*06 haplotypes, whereas no associations have been described with any HLA class I allele.
The coexistence of anti-La (SS-B) and anti-Ro (SS-A) autoantibodies in pSS is probably explained by intermolecular spreading of autoimmunity toward different components of the La/Ro ribonucleoprotein (RNP).
These data demonstrate that anti-Ro(SS-A)/La(SS-B) positive Sjogren's/lupus overlap patients and neonatal lupus syndrome mothers are immunogenetically closely related to each other and appear to be more closely related to both primary Sjogren's syndrome and subacute lupus erythematosus, than to classical systemic lupus erythematosus.
Our data support a role for the TNFalpha10 allele in primary Sjögren's syndrome, particularly those forms with joint symptoms and anti-Ro(SS-A) antibodies.
Primary Sjögren's syndrome (SS) is a systemic autoimmune inflammatory disease characterized by focal lymphocytic infiltrates in the lachrymal and salivary glands and autoantibodies against the SSA/Ro and SSB/La antigens.
No relationship was found between anti-cN-1A reactivity and the presence or absence of anti-Ro52, anti-nucleosome, and anti-dsDNA reactivity in both pSS and SLE.
RF should be considered as a prognostic, but not diagnostic, factor in patients with pSS, as it is associated with more severe disease course (sicca eye symptoms, ESSDAI) and parameters (production of gammaglobulins, ANA, anti SS-A, anti-SS-B autoantibodies) indicating increased B cell activity.