To better understand the role of CTLA4IgG in primary Sjögren's syndrome (pSS), we generated a recombinant adeno-associated virus vector serotype 2 (AAV2) expressing a chimera of mouse CTLA-4 fused with a human immunoglobulin (AAV2-CTLA4IgG) and observed the effect of this molecule in C57BL/6.NOD-Aec1Aec2 mice, an animal model of pSS.
An immunoblot approach applied to independent sample sets confirmed the pSS associated up-regulation of β2-microglobulin (in PS) and down-regulation of carbonic anhydrase VI (in WS) and BPIFB2 (in PS).
BST-2 was significantly increased in pSS labial glands and was positively correlated with the VAS value for parotid gland swelling and rheumatoid factor and β2-microglobulin serum levels.
The most likely gene related to the D6S439 chromosomal location appears to be BAK-1 , which codes for Bak protein, expressed in salivary gland's infiltrate from patients with primary SS but not in controls.
Three blinded operators (one pathologist and two rheumatologists with different years of experience in pSS MSG assessment) assessed 50 MSGs of which one slide was stained with haematoxylin and eosin (H&E) and consecutive slides were processed to investigate CD3/CD20, CD21 and Bcl-6 expression.
In this study, we investigated whether SNPs in the BANK1 (rs4522865, rs17266594, and rs10516487) and in the FAM167A-BLK region (rs2736340, rs13277113) could be associated with pSS in Chinese Han.
Weak associations were observed when the SNPs in TNFSF4 (rs2205960, rs844648 and rs704840) and FAM167A-BLK (rs7812879, rs2254546 and rs2618479) were directly analyzed or analyzed under dominant model between pSS and controls (all P<0.05).
EBF1, BLK and TNFSF4 are all involved in B-cell differentiation and activation, and we conclude that polymorphisms in several susceptibility genes in the immune system contribute to the pathogenesis of primary SS.
In the genotype analysis, the frequency of the GCC/ATA genotype was higher (29 vs 11%, P=0.001) and that of the ACC/ACC genotype lower (3 vs 12%, P=0.044) in patients with primary SS compared with healthy controls.
An immunoblot approach applied to independent sample sets confirmed the pSS associated up-regulation of β2-microglobulin (in PS) and down-regulation of carbonic anhydrase VI (in WS) and BPIFB2 (in PS).
BST-2 was aberrantly expressed in pSS patients, and expression in labial glands was positively correlated with important clinical characteristics; thus, it may be a potential biomarker of pSS activity.
We confirm the strong influence of immunological markers on the phenotype of primary SjS at diagnosis in the largest multi-ethnic international cohort ever analysed, with a greater influence for cryoglobulinaemic-related markers in comparison with Ro/La autoantibodies and ANA.
The prevalence of ANA was increased in most patients with systemic especially in neuropathy (NP), hemolytic anemia (HA), primary Sjogren's syndrome (pSS), dermatomyositis (DM), thrombocytopenia (Tb), systemic sclerosis (SSc), ANCA-associated vasculitis (AAV), AP, Renal impairment (RI), SLE, and mixed connective tissue disease (MCTD).
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.
BMS-986142 is a potent and highly selective reversible small molecule inhibitor of BTK currently being investigated in clinical trials for the treatment of both RA and primary Sjögren's syndrome.
Likewise, BTK protein was increased in B cells from a major fraction of patients with primary SS and correlated with serum rheumatoid factor levels and parotid gland T cell infiltration.
It is yet to be shown whether the lack of expression of C4A genes in Japanese patients with primary SS is due to point mutations, or to small deletions or insertions that were not detected by the RFLP approach.
An immunoblot approach applied to independent sample sets confirmed the pSS associated up-regulation of β2-microglobulin (in PS) and down-regulation of carbonic anhydrase VI (in WS) and BPIFB2 (in PS).
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.