CTLA‐4 polymorphisms in Thai patients with rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis

Abstract

Aims: Studies on polymorphisms of the cytotoxic T lymphocytes associated antigen-4 (CTLA-4) genes in rheumatic disease patients are limited in Southeast Asia. This pilot study aimed to determine CTLA-4 polymorphisms in Thai patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), and correlate them with serology. Method: One-hundred RA, 70 SLE and 50 SSc patients, and 99 healthy controls (HCs) were included in this study. Polymorphisms of the CTLA-4 gene at +49A/G, −318C/T, −1661A/G and −1722T/C loci were determined by polymerase chain reaction restriction fragment length polymorphism methods. Patient serum samples were determined as follows: RA (rheumatoid factor [RF] and anticyclic citrullinated peptide [anti-CCP]), SLE (antinuclear antibodies [ANA], anti-double-stranded DNA [anti-dsDNA], anti-Smith [anti-Sm], anti-ribonucleoprotein [anti-RNP], and anti-Sjögren's syndrome antigen A [SSA]), and SSc (ANA, anti-RNP, anti-SSA, anti-topoisomerase-1 [anti-Scl70], and anti-centromere antibodies [ACA]).Results: Among the 4 loci studied (+49A/G, −318C/T, −1661A/G and −1722T/C) only the A allele frequency at the +49A/G was significantly higher in the RA patients than their HCs (47.25% vs 35.86%, P = .029, odds ratio [OR] 1.60; 95% CI 1.04-2.47). It also was significantly higher in the subgroup of RA patients with positive RF and anti-CCP than their HCs (47.50% vs 35.86%, P = .020, OR 1.62; 95% CI 1.06-2.47 and 48.89% vs 35.86%, P = .012, OR 1.71; 95% CI 1.11-2.64, respectively). No polymorphisms at these 4 loci were observed in SLE or SSc patients. Conclusion:The A allele at +49A/G locus of the CTLA-4 gene was associated with RA in Thais.

Discovery of a shared therapeutic target in granulomatosis with polyangiitis and gastric tumor microenvironment

“…The findings of this study suggest that SERPINA1 may be a tumor‐promoting factor in gastric cancer, which is in line with previous studies 2 . In addition, the authors used protein–protein interaction analysis to investigate the relationship between SERPINA1 and CTLA4, a protein that plays an important role in regulating the immune system 3 . We found that SERPINA1 and CTLA4 have crosstalk through the intermediate regulators PLG and ELANE proteins.…”

“…2 In addition, the authors used proteinprotein interaction analysis to investigate the relationship between SERPINA1 and CTLA4, a protein that plays an important role in regulating the immune system. 3 We found that SERPINA1 and CTLA4 have crosstalk through the intermediate regulators PLG and ELANE proteins. Furthermore, the authors analyzed the relationship between SERPINA1 and CTLA4 using the TIMER immune database and found a strong positive correlation between the 2, as shown in Figure 2.…”

Performance of eye sign combined with increased interleukin‐6 in cerebrospinal fluid in patients with neuropsychiatric lupus erythematosus

“…Polymorphisms of multiple genes and molecules have been shown to be associated with SLE, such as the cytotoxic T lymphocyte associated antigen‐4 ( CTLA4 ) gene 29 and sirtuin‐1 ( SIRT1 ) 30 . The interleukin pathways have been commonly implicated in the development of SLE 31 .…”

Rheumatic manifestations in cancer patients treated with immune checkpoint inhibitors

“…Single nucleotide polymorphisms (SNPs) within the CTLA-4 gene are most commonly asso-ciated with aetiopathogenesis of these diseases. An emerging variation in the DNA sequence involves the substitution of a single nucleotide for another nucleotide [7]. The CTLA-4 gene has many variants and polymorphic forms, among which the most commonly examined was +49A/G polymorphism.…”

“…The CTLA-4 gene has many variants and polymorphic forms, among which the most commonly examined was +49A/G polymorphism. In a study by Louthrenoo et al [7], 100 RA patients, 50 SSc patients, 70 SLE patients and 99 healthy controls were analysed for CTLA-4 SNPs. It was found that out of the four CTLA-4 loci (+49A/G, -318C/T, -1661A/G and -1722T/C), the A allele polymorphism at the +49A/G locus was significantly more frequent in RA patients.…”