Association of CD28 IVS3 +17T/C Polymorphism with Soluble CD28 in Rheumatoid Arthritis

Abstract

Objective: Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology in which inflammatory pathology involves T cell activation and the CD28 costimulatory molecule involved in T cell presentation. The gene includes the CD28 IVS3 +17T/C polymorphism that could be associated with susceptibility to RA whereas the soluble concentrations of CD28 (sCD28) could be related to clinical activity. Methods: We investigated the CD28 IVS3 +17T/C polymorphism in 200 RA patients and 200 healthy subjects (HS). Furthermore, we quantified the sCD28 concentrations in 77 samples of each group. We applied indexes focused to determine the activity and disability (DAS28 and Spanish HAQ-DI, respectively) in RA patients. Methods: We investigated the CD28 IVS3 +17T/C polymorphism in 200 RA patients and 200 healthy subjects (HS). Furthermore, we quantified the sCD28 concentrations in 77 samples of each group. We applied indexes focused to determine the activity and disability (DAS28 and Spanish HAQ-DI, respectively) in RA patients. Results: RA patients had significantly higher frequencies of the CD28 T allele compared to HS (p = 0.032 OR = 1.59, C.I. 1.02–2.49). In addition, the IVS3 +17 T/T genotype frequency was also increased in RA vs. HS (p = 0.026). The RA patients showed higher sCD28 serum levels than HS (p = 0.001). Carriers of the T/T genotype in RA patients showed higher sCD28 levels than C/C carriers (p = 0.047). In addition, a correlation between sCD28 and Spanish HAQ-DI (correlation, 0.272; p = 0.016), was found. Conclusion: The T allele in CD28 IVS3 +17T/C polymorphism is associated with a susceptibility to RA in Western Mexico. In addition, increased sCD28 levels are related to T/T genotype in RA patients.

Expression patterns of CD28 and CTLA‐4 in early, chronic, and untreated rheumatoid arthritis

“…Other important findings of this study were a trend of higher sCD28 levels in the RA patient groups compared with CS, and a significantly decrease in these levels in chronic RA patients compared with early RA patients. These findings are related to those previously reported in the study . High levels of sCD28 in RA patients could suggest a regulatory mechanism to compensate the activation in T cells.…”

Polymorphisms in CD28, CTLA-4, CD80 and CD86 genes may influence the risk of multiple sclerosis and its age of onset

“…In consequence it could influence immune homeostasis by disturbing balance between different isoforms of CD28 protein (Chen et al, 2012). In fact, the study performed by Ledezma-Lozano et al (Ledezma-Lozano et al, 2011) revealed that in group of rheumatoid arthritis patients, TC genotype in rs3116496T N C was associated with the decreased level of soluble CD28 form in comparison to TT. As far as rs6641T N G polymorphism is concerned, in the literature there is no data considering its function and association with MS susceptibility.…”

Investigation of CD28 Gene Polymorphisms in Patients with Sporadic Breast Cancer in a Chinese Han Population in Northeast China

“…rs3116496, lead to the unbalanced expression of various CD28 protein isoforms by aberrant splicing, which leads to altered immune function. In line with this hypothesis, a report comparing sCD28 expression of each rs3116496 genotype in rheumatoid arthritis patients found higher sCD28 levels in TT carriers than in those with the TC genotype [21]. Further studies of the potential mechanisms underlying intronic polymorphisms, on CD28 pre-mRNA splicing, will therefore be interesting.…”

“…The relationship between the CD28 rs3116496 polymorphisms and susceptibility to various diseases, including cancer, has been previously investigated. Bechet’s disease [22], rheumatoid arthritis [21], and cervical cancer [23], [24], [25], [26], [27] are all known to be associated with the rs3116496 polymorphism. It was reported that the rs3116496 TT genotype was associated with a low risk of cervical cancer in a Chinese Han and in a Swedish population, respectively [23], [24].…”

“…The human CD28 gene is located in the chromosome 2q33 region. Polymorphisms in the CD28 gene were previously shown to be genetically associated with autoimmune diseases, such as rheumatoid arthritis and Bechet’s disease [21], [22]. Several compelling reports characterized the association between this susceptibility loci and cervical cancer risk in different ethnic groups [23], [24], [25], [26], [27].…”