Genotypes of ABCA7 and HA-1 SNP were determined in three distinct Caucasian populations of patients with primary Sjögren's syndrome and ethnically matched controls.
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.
Plasma and salivary samples were collected from 28 patients with pSS according to 2012 ACR and/or 2016 ACR/EULAR criteria (27 females, mean age 64.4±10.1 years, mean disease duration 10.7±6.9 years), and from 23 healthy subjects used as controls.
The immunological profile includes only anti-Ro antibodies, while positivity for antinuclear antibodies and rheumatoid factor or isolated anti-La was excluded due to a lack of specificity.The 2016 ACR/EULAR criteria are suitable for early identification of SS, providing patients with the opportunity of enrollment in clinical trials for new specific treatment.
We observed similar results when using the new ACR-EULAR classification criteria or the previously used American-European Consensus Group (AECG) classification criteria for pSS.
Historically, the clinical role of salivary gland histopathology, most commonly performed on labial salivary gland biopsies, has been confined to the clinical classification and diagnosis of pSS whereby according to the ACR-EULAR a positive histopathology finding is a requirement for the diagnosis of pSS in the absence of anti-Ro/SSA antibodies.
The reactivity of recombinant antibodies isolated from single B cells from patients with primary SS and LPD was tested using an enzyme-linked immunosorbent assay.
Our observations demonstrated that p63 nuclear labeling in pSS MECs is preserved whereas α-SMA cytoplasmic staining is strongly and significantly reduced when compared with healthy SGs; the digital images analysis quantification of the expression of labeled α-SMA and p63 protein in the healthy and pSS MECs salivary tissues, led to results suggesting a loss of mechanical support for acini and ducts in pSS, correlated, probably, with the reduction of salivary flow that features one important aspect of pSS disease.
We identified <i>HIF1A Pro582Ser T</i> allele and <i>C</i>/<i>T</i> genotype as well as <i>AKNA -1372C>A</i> polymorphism A/A genotype as genetic factors associated with pSS.
In this study, four proteins including cofilin-1, alpha-enolase, annexin A2 and Rho GDP-dissociation inhibitor 2 (RGI2) were found to be over-expressed in pSS and pSS/MALT by 2D gel electrophoresis/mass spectrometry, and the finding was verified by the microarray analysis and western blotting results.
The most striking observation was the discovery of AQP4 localization in myoepithelial cells (MECs) that surround acini lobules and intercalated ducts, and the demonstration of AQP4-downregulated immunoreactivity in pSS MECs.
The expression levels of salivary anti-cofilin-1, anti-alpha-enolase and anti-RGI2 were found to be the highest in pSS/MALT patients and lowest in healthy controls.
These results suggest that the presence of the GCC haplotype or the GCC/ATA genotype and the absence of the ACC haplotype of the IL-10 gene are associated with an increased susceptibility to primary SS.
Immunotherapy of primary Sjögren's syndrome is promising, since autoimmunity in NOD mice with Sjögren's syndrome seems to be uniquely susceptible to such treatment even late in disease.