International Journal of Immunogenetics最新文献

Genetic and nongenetic factors are involved in the pathogenesis of immune-mediated inflammatory diseases (IMIDs). The best-known genetic factor for susceptibility to IMIDs is the human leukocyte antigen (HLA). The aim of the present study was to evaluate the association of HLA class II genes with the risk of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc) in the Paraguayan population. We included 254 patients with IMIDs (101 SLE, 103 RA, and 50 SSc) and 50 healthy controls. The haplotypes of five genes corresponding to HLA class II genes and their relationship to the IMIDs studied were determined. Note that 84.6% were women, with a mean age of 43.4 ± 14 years. Among the associated HLA alleles, we found the previously identified risk factors in other populations like HLA-DRB1*03:01 and HLA-DRB1*14:02 for RA, as well as new ones not previously identified, such as DPA1*02:01 for SLE and, DB1*02:01 for RA and SSc. In the genetic association analysis, already known associations have been replicated, and unpublished associations have been identified in Paraguayan patients with IMIDs. This is the first genetic association study in Paraguayan patients with IMIDs.

Rheumatoid arthritis (RA) affects approximately 1.5% of the population worldwide and 0.5–3.3% of the Mexican population. The presence of rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) and anti-carbamylated protein (anti-CarP) antibodies has been described in populations at risk of RA development, such as first-degree relatives (FDR). Anti-CarP antibodies are present in RA patients (44%), FDR of RA patients (18%) and healthy controls (4.7%). Anti-CarP antibodies have not been described in FDR of the Mexican population. The objective of this study was to determine the prevalence of Rheumatoid Factors (RF) isotypes, ACPA and anti-CarP antibodies isotypes in FDR of RA patients. An observational, cross-sectional study, in an FDR of RA cohort, was performed. We measured IgA, IgG and IgM isotypes of RF, ACPA and anti-CarP antibodies. A total of 144 FDRs from 99 RA patients were enrolled. The prevalence of anti-CarP antibodies was 2.8% for IgA, 4.2% for IgG, whereas IgM was not detected. The serologic association was for RF/ACPA 4.48%, RF/anti-CarP 2.7%, FR 64.5%, ACPA 1.3%, ACPA/anti-CarP 0.69%, anti-CarP 3.4%, and no RF/ACPA/anti-CarP was observed. We found a low prevalence of anti-CarP antibodies in our cohort of FDR of RA patients, but the prevalence of ACPA and RF were higher than other cohorts previously reported.

HLA-DPA1 intralocus recombination between DPA1*04:01:01:03 and DPA1*01:03:01:27, or closely related other alleles, results in a novel allele HLA-DPA1*01:03:43.

Diabetic retinopathy (DR) is a common microvascular complication of diabetes and the leading cause of blindness at working age. DR is considered to be a chronic low-grade inflammatory subclinical disease, and its pathogenesis is related to genetic and environmental factors. Interleukin (IL)-1 is an important inflammatory cytokine. An association between DR and the rs16944 (IL-1B-511) T>C gene polymorphism has not been reported. The aim of this study was to investigate the association between the rs16944 T>C gene polymorphism and DR in the Han population in southwest China. Participants in this study were 272 patients with DR, 274 patients with type 2 diabetes mellitus (T2DM), and 335 healthy controls (NC). The polymerase chain reaction-restriction fragment length polymorphism method was used to detect the rs16944 T>C genotype of participants. The distribution frequencies of the rs16944 T>C genotype and allele were significantly different among the three groups (p < .05). The distribution frequency of TT, CT, CC genotype (χ² = 9.893, p = .007; χ² = 6.567, p = .037) and each allele (χ² = 5.585, p = .018; χ² = 9.187, p = .002) in the DR group was significantly different from the NC and T2DM groups, respectively. Logistic regression analysis showed that the TT + CT genotype was a risk factor for DR, with an odds ratio of 1.731 (95% confidence interval 1.140–2.627, p = .01). The rs16944 T>C gene polymorphism may be associated with DR, and the TT+CT genotype may increase the risk of DR.

Endometriosis is an inflammatory disease characterized by the presence of ectopic endometrial tissue, immune cell dysfunction and abnormal cytokine secretion. In addition to immunological factors, genetic variations that influence endometriosis severity and cytokine expression levels play important roles in the pathogenesis of this disease. Interleukin-12 (IL-12), specifically its p40 subunit encoded by IL-12B gene and the interleukin-12 receptor β1 (IL-12Rβ2) chain of its receptor, as well as interleukin-27 (IL-27) are important in the establishment of endometriosis. So, in this study, we measured IL-12 and IL-27 serum levels and investigated the possible links between IL-12B rs3212227, IL-12Rβ2 rs3790565 and IL-27 rs153109 polymorphisms and the risk of developing endometriosis in a group of Iranian women. In this case-control study, 162 endometriosis patients and 151 healthy women were included and tested for the aforementioned polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The enzyme-linked immunosorbent assay (ELISA) method was also used to measure IL-12 and IL-27 serum levels. Although there was no statistically significant association between the genotypes and alleles of the studied polymorphisms and the development of endometriosis in general, the AA genotype of IL-12B rs3212227 showed a significant association with uterine endometriosis when compared to AC+CC genotypes (p = .04, CI = 0.270–0.988, OR = 0.517). Indeed, the AA genotype of the IL-12B rs3212227 single nucleotide polymorphism (SNP) may be linked with a lower risk of developing uterine endometriosis. There was no significant difference in IL-27 levels between the two studied groups (p = .49), and IL-12 levels were undetectable in both groups. In conclusion, the AA genotype of IL-12B rs3212227 might be associated with a decreased risk of uterine involvement in endometriosis patients.

Coronavirus disease-2019 (COVID-19) is pro-inflammatory disorder characterized by acute respiratory distress syndrome. Interleukin-6, a cytokine secreted by macrophages, which mediates an inflammatory response, is frequently increased and associated with the severity in COVID-19 patients. The differential expression of IL6 cytokine in COVID-19 patients may be associated with the presence of single nucleotide polymorphisms (SNPs) in regulatory region of cytokine genes. The aim of this study is to investigate the role of two promoter polymorphisms of the IL6 gene (–597G > A and –174G > C) with the severity of COVID-19. The study included 242 patients, out of which 97 patients with severe symptoms and 145 patients with mild symptoms of COVID-19. Genotyping of two selected SNPs, rs1800795 (–174G > C) and rs1800797 (–597G > A) of promoter region of IL6 gene, was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In our study, individuals with GC genotypes of IL6 (–174G > C) polymorphism showed significantly higher risk of severity [adjusted odds (OR) 3.86, p <.001] but we did not observe any association of COVID-19 severity with rs1800797 (–597G > A) polymorphism. The COVID-19 severity was significantly higher in individuals having ‘C’ allele of IL6 (–174G > C) polymorphism (p = .014). Linkage disequilibrium between rs1800795 (–174G > C) and rs1800797 (–597G > A) showed that individuals having AC* haplotype significantly association with COVID-19 severity (p = .034). Our results suggest that ‘C’ allele of rs1800795 (–174G > C) polymorphism of IL6 may be the risk allele for severity of COVID-19 in North Indian population.

Asthma, a chronic inflammatory disorder of the lungs and airways, typically results from a combination of multiple environmental and genetic factors. Human leucocyte antigen (HLA) region on chromosome 6p21 encodes the most highly polymorphic loci in the human genome, encoding genes with central roles in the immune function where HLA loci are strongly associated with various immune-mediated diseases such as autoimmunity, allergies and infection. The alleles of HLA class II genes such as DRB1 and DQB1 are the key genetic markers in the development of asthma and have been extensively studied in different ethnicities of the world population. However, the genetic screening of HLA class II alleles and haplotypes in Pakistani asthmatics has not been studied so far. The aim of the present study was to screen the HLA class II DRB1 and DQB1 alleles in asthma cases and controls in a Pakistani population. Seven hundred and two healthy controls and asthma patients were genotyped for HLA class II by sequence-specific polymerase chain reaction assays. The HLA-DRB1 and HLA-DQB1 allele and haplotype frequencies were calculated, and their risk or protective association with asthma was determined. Two-locus haplotypes of DRB1 and DQB1 alleles were imputed using Arlequin version 3.1 software. The signals of association with asthma were stronger at the DQB1 locus as compared to DRB1. HLA DQB1*03:03:02 (odds ratio [OR] = 2.42, 95% confidence interval [CI] = 1.34–4.25) was significantly associated with an increased risk of asthma, as was the haplotype comprised allele DRB1*07:01-DQB1*03:03:02 (OR = 2.40, 95% CI = 1.25–4.62). In contrast, DQB1*06 (OR = 0.39, 95% CI = 0.22–0.70) and DQB1*06:02 (OR = 0.27, 95% CI = 0.10–0.71) emerged as protective alleles for asthma. Our data concludes that the HLA DQB1*03:03:02 allele was a risk allele for asthma, whereas two DQB1 alleles, DQB1*06 and DQB1*06:02, were associated with asthma protection. Our findings highlight a prominent role for HLA-DQB1 alleles in asthma pathogenesis in studied Pakistani cases. More studies, especially with a larger study cohort are needed to confirm the utility of HLA DQB1*03:03:02 as a predictive marker.