ICOS Gene Polymorphisms (IVS1 + 173 T/C and c. 1624 C/T) in Primary Sjögren’s Syndrome Patients: Analysis of ICOS Expression

Abstract

Background: Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease, which affects exocrine glands. T cell activation is a trigger mechanism in the immune response. Hyperreactivity of T cells and antibody production are features in pSS. ICOS can be critical in the pathogenesis of pSS. Methods: A total of 134 pSS patients and 134 control subjects (CS) were included. Genotyping was performed by PCR-RFLP. ICOS mRNA expression was quantified by real-time PCR, and CD4+ ICOS+ T cells were determined by flow cytometry. Results: The ICOS IVS1 + 173 T>C polymorphisms were not associated with susceptibility to pSS (p = 0.393, CI = 0.503–1.311). However, the c.1624 C>T polymorphism was associated with a reduction in the risk of development of pSS (p = 0.015, CI = 0.294–0.884). An increase in ICOS mRNA expression in patients was observed (3.7-fold). Furthermore, pSS patients showed an increase in membranal-ICOS expression (mICOS). High expression of mICOS (MFI) was associated with lymphocytic infiltration. Conclusions: The IVS1 + 173 polymorphism is not a genetic marker for the development of pSS, while c.1624 T allele was associated with a low risk. However, elevated mICOS expression in pSS patients with high lymphocytic infiltration was found. ICOS may have an important role in the immunopathogenesis of pSS and should be analyzed in T cell subsets in pSS patients as a possible disease marker.

ICOS gene polymorphisms in systemic lupus erythematosus: A case–control study

“…In the gene expression study, we showed a decrease in ICOS mRNA expression in SLE patients compared to HC. Our results do not corroborate with a recent study, which showed that ICOS mRNA expression levels are high in pSS patients compared to controls (García‐Espinoza et al., 2022). The low expression in our patients is probably related to the therapeutic effects of corticosteroids.…”

“…Our results are in agreement with the study of García‐Espinoza et al. (2022), who found a CC genotype frequency of 1% for the rs10932029 polymorphism in the western Mexican population. In addition, Haimila et al.…”

“…On the other hand, PC-2 showed an existing relationship between rs10932029 and disease duration. A recent study performed on patients with pSS showed that patients with the TT genotype had a very high relative mRNA expression compared to controls, whereas patients with the CT genotype had a lower mRNA expression compared to healthy subjects (García-Espinoza et al, 2022). Likewise, Woszczyk et al (2020) showed in their study on myeloma patients, that the ICOS ISV1+173T > C polymorphism does not influence the level of ICOS mRNA in CD4 + cells but does influence the expression of CTLA-4 mRNA.…”

“…On the other hand, PC‐2 showed an existing relationship between rs10932029 and disease duration. A recent study performed on patients with pSS showed that patients with the TT genotype had a very high relative mRNA expression compared to controls, whereas patients with the CT genotype had a lower mRNA expression compared to healthy subjects (García‐Espinoza et al., 2022). Likewise, Woszczyk et al.…”

Expression of ICOS in the salivary glands of patients with primary Sjogren's syndrome and its molecular mechanism

“…enhanced expression of icoS-expressing cd3+ T cells may suggest that the systemic lupus erythematosus (SLE) patients are at a more severe inflammatory status (22). Previous studies have reported increased icoS protein and mrna expression levels in the peripheral blood of patients Expression of ICOS in the salivary glands of patients with primary Sjogren's syndrome and its molecular mechanism with pSS (23,24). The present study found that the expression of icoS was shown to affect saliva weight and aquaporin 5 (AQP5) expression; however, the specific downstream signal transduction constituents involved remain unknown.…”