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Background and Aim: The immune response to the BNT162b2 COVID-19 vaccine among people is not the same. Genetic polymorphism in inhibitory immune checkpoints may have an important role in immune response after vaccination; therefore, we aimed to demonstrate the role of CTLA-4 rs733618 gene polymorphism and the amount of circulating CTLA4 in individuals vaccinated with the BNT162b2 vaccine following the booster dose. Materials and Methods: This research is a cross-sectional study performed on 180 healthy adults (above 18 years old) vaccinated with the BNT162b2 COVID-19 vaccine 21-30 days after the second dose at the community-dwelling from December 2021 to April 2022. After DNA extraction from the sample's blood, Allele-specific polymerase chain reaction (ASPCR) was developed to detect single nucleotide polymorphisms of CTLA-4 rs733618. The levels of IgG in the serum, which are directed towards the spike protein-1 and soluble CTLA-4, were quantified using an Enzyme-linked Immunosorbent Assay (ELISA). Results: The current study showed no significant association in CTLA-4 rs733618 genotype distribution and immune response to the BNT162b2 vaccine, Furthermore, there was a highly significant difference between CTLA-4 serum levels and CTLA-4 rs733618 genotype frequency. Conclusion: CTLA-4 -1722 T/C rs733618 is not significantly related to immunological response to the BNT162b2 vaccine. The level of s-CTLA-4 production may be affected by CTLA-4rs733618 polymorphism. rs733618 (T/C) and rs733618(C/C) genotypes significantly related with high level of s-CTLA-4, while rs733618 T/T genotype related with low level of s-CTLA-4. [ABSTRACT FROM AUTHOR]

Introduction. The main treatment of autoimmune thyroiditis (AIT) is conservative. However, there are patients with AIT in whom surgical treatment is mandatory. The growing experience and reports of surgical intervention with newer indications challenges this traditional view of AIT. The objective of the study was to determine the choice of surgery volume in patients with nodular goiter and AIT, taking into account the activity of apoptosis, index of proliferative activity and polymorphisms of cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene. Material and methods. 95 patients with nodular goiter and autoimmune thyroiditis (NGAIT) were included in the study. We determined the activity of the apoptosis index of proliferative activity and gene polymorphism of CTLA-4. Results. The correlation analysis of markers used to optimize surgical treatment, namely the choice of the surgery volume in patients with NGAIT, showed that the studied tests are objective and reliable for the long-term results of surgical treatment: the volume of the thyroid gland not affected by the nodes less than 10 cm3, the level of antibodies to thyroid peroxidase (TPO Ab) 43%, IIRC Bcl-2 50%; AA and AG-genotype of the CTLA-4 gene. Conclusions. The study allowed to determine new criteria for selecting the volume of surgery in patients with NGAIT.

Background: The prevalence of hepatitis C virus (HCV) infection is increasing worldwide. Cytotoxic Tlymphocyte-associated protein 4 (CTLA-4) may play a role in the intensity of the disease. The aim of this study was to evaluate the association between genetic variants of the CTLA-4 and HCV infection. Methods: Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was performed as the genotyping assay at four different positions (+49 A>G, -318 C>T, -1722 T>C, and - 1661 A>G). Haplotypes were analyzed using PHASE software. Sixty-five HCV patients and 65 healthy individuals as controls who were referred to the hepatitis clinic in Mashhad, Iran, were recruited. Genomic DNA was extracted from whole blood of participants. Results: In a dominant analysis model of the -1661 position (GG vs. AA+AG), the AA genotype was more common in controls than in patients (adjusted P = 0.0003; OR = 0.15, 95% CI = 0.051 -0.42). The GCAT haplotype was also more prevalent in controls than in patients (adjusted P = 0.01; OR = 0.40, 95% CI = 0.20-0.81). Furthermore, the ACGT/ACGT diplotype was more common in controls than in patients (P = 0.0037; OR = 0.15, 95% CI = 0.04-0.54). In addition, the ACGT/ACAT diplotype was more frequent in patients than controls (adjusted P =0.003; OR = 2.48, 95% CI = 1.37-4.50). Conclusions: Our results indicated that polymorphisms in CTLA-4 and certain haplotypes may affect the risk of HCV infection in our population, although a larger sample size may be required to confirm this association. [ABSTRACT FROM AUTHOR]

CTLA-4 gene is considered to be one of the strongest factors determining the predisposition to antithyroid antibody (Ab) production. The aim of the study was to evaluate the association of the polymorphism A/G of exon 1 of CTLA-4 gene and antithyroid Ab level in children with Hashimoto's thyroiditis (HT). Material and Methods: 45 children with HT (aged 14.9 ± 2, range 8.1-7.9) and 55 healthy controls (aged 14.8 ± 2.34, range 8.0-17.4) were enrolled. Controls were euthyroid and free from any autoimmune disease. CTLA-4 gene (+49)A/G polymorphism was evaluated by a single-strand conformation polymorphism method and restriction fragment-length polymorphism. Results: The frequency of GG genotype in HTchildren was significantly higherthan in controls: 31 vs. 14.5% respectively (p < 0.04, OR = 2.65, Cl = 0.99-7.06). Anti-Tg Ab titers were higher in patients homozygous for Gallele than with AAgenotype.TheGG genotype seemed to be protective from hypothyroidism at the moment of HT diagnosis, but this observation was not statistically confirmed. Conclusions: Our study provides the evidence supporting the association between CTLA-4 gene (+49)A/G polymorphism and the susceptibility to HT in Polish children and confirms the existence of a link between (+49)A/G polymorphism and anti-Tg Ab level. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the polymorphisms of exon 1 (+49A/G) and promoter (−318C/T and −651C/T) regions of the CTLA-4 gene in 133 Japanese patients with conventional/classical multiple sclerosis (MS) and 156 healthy controls. Patients with optico-spinal MS (OSMS) or atypical clinical attacks were excluded from the study. There was no significant difference in the distribution of polymorphisms between patients and controls. Furthermore, there were no associations between polymorphisms and clinical characteristics, such as age at onset, disease prognosis, and HLA profiles. Our results suggest that CTLA-4 gene polymorphisms are neither conclusively related to susceptibility nor to the clinical characteristics of MS, especially in Japanese patients with conventional/classical form and clinical features identical to those of their counterparts in Western countries. [Copyright &y& Elsevier]

This study was carried out to investigate the association of a polymorphism of the CTLA-4 gene, at position 49 of exon 1, with schizophrenia in the Korean population. Among Korean patients diagnosed with schizophrenia according to DSM-IV, 116 patients who met the selection criteria were recruited for the study. One hundred and forty-nine normal healthy Koreans from the Catholic Hemopoietic Stem Cell Information Bank, were used as a normal control group. DNA was extracted from whole blood using proteinase K and the CTLA-4 gene region was amplified by polymerase chain reaction. Geneo typing was performed by single strand conformation polymorphism (SSCP). The genotype and allele distribution in patients with schizophrenia was significantly different from that seen in the control group. This study suggests a putative role of the CTLA-4 gene polymorphism at position 49 of exon 1 for schizophrenia in the Korean population, although the detailed mechanisms remained to be elucidated. [Copyright &y& Elsevier]

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is an important molecule in the down-regulation of T-cell activation. A study was undertaken to evaluate the association of the CTLA-4 gene polymorphisms −319C/T, +49A/G, (AT)n, CT60A/G and Jo31G/T with the levels of membrane CTLA-4 (mCTLA-4) and cytoplasmic CTLA-4 (cCTLA-4) in CD4+ T lymphocytes from patients with multiple sclerosis (MS) and with susceptibility to MS, and the course of the disease. It was found that the Jo31GG and CT60GG genotypes were associated with decreased mean fluorescence intensity (MFI) of total CTLA-4 (mCTLA-4 + cCTLA-4) molecules in CD4+ T cells from both relapsing-remitting (RR) and secondary progressive (SP) MS patients compared with others. Consequently, possessing the Jo31G allele and/or the CT60G allele were associated with susceptibility to MS. The percentages of cells expressing mCTLA-4 and cCTLA-4 in RR patients were higher in carriers of the alleles non-predisposing to MS (namely CT60A and Jo31T), but the percentages of corresponding cells were unexpectedly significantly lower in SP patients than in RR patients. Increased risk of paresthesia and pyramidal signs as a first manifestation of disease, and earlier transition to the SP form in those patients, was also noted. It is hypothesized that the decreasing frequencies of cells expressing immunosuppressive mCTLA-4 and cCTLA-4 in carriers of alleles non-predisposing to MS (i.e. CT60A and Jo31T) may lead to inadequate down-regulation of ongoing T-cell responses in these patients and, as a consequence, earlier progression of disease from the RR form to the SP form. [ABSTRACT FROM AUTHOR]