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

Background: Primary Sjogren'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.

Automated summary

This study found that the IVS1 + 173 polymorphism of the ICOS gene is not a genetic marker for the development of pSS, while the c.1624 C>T polymorphism is associated with a reduced risk. Additionally, increased membranal-ICOS expression was observed in pSS patients with high lymphocytic infiltration. These findings suggest that ICOS may play an important role in the pathogenesis of pSS and should be further studied as a possible disease marker in T cell subsets of pSS patients.