International Journal of Immunogenetics最新文献

Toll-like receptors (TLRs) play an important role in innate immunity. Previous studies have shown that single nucleotide polymorphisms (SNPs) in the genes coding for these innate immune molecules can affect susceptibility to and the outcome of certain diseases. The aim of the present study was to examine the clinical relevance of well-studied TLR1–4 SNPs in individuals who are prone to infections. Four functional SNPs, TLR1 rs5743618 (1805C > A, Ser602Ile), TLR2 rs5743708 (2258G > A, Arg753Gln), TLR3 rs3775291 (1234C > T, Leu412Phe) and TLR4 rs4986790 (896A > G, Asp299Gly), were analysed in 155 patients with recurrent respiratory infections (n = 84), severe infections (n = 15) or common variable immunodeficiency (n = 56), and in 262 healthy controls, using the High Resolution Melting Analysis method. Polymorphisms of TLR2 rs5743708 (odds ratio [OR] 3.16; 95% confidence interval [CI] 1.45–6.83, p = .004, ap = .016) and TLR4 rs4986790 (OR 1.8; 95% CI 1.05–3.12, p = .028, ap = .112) were more frequent in patients with recurrent or severe infections than in controls. Interestingly, seven patients were found to carry both variant genotypes of TLR2 and TLR4, whereas none of the control group carried such genotypes (p  ≤ .0001). Moreover, TLR2 polymorphism was associated with increased risk for acute otitis media episodes (OR, 3.02; 95% CI 1.41–6.47; p = .012). This study indicates that children and adults who are more prone to recurrent or severe respiratory infections carry one or both variant types of TLR2 and TLR4 more often than control subjects. Genetic variations of TLRs help explain why some children are more susceptible to respiratory infections.

Vitamin D status has been involved with coronavirus disease 19 (COVID-19) severity. This may be mediated by vitamin D metabolism regulatory genes. Of interest is the vitamin D receptor (VDR) gene, which has been previously associated with other inflammatory and respiratory diseases. In order to investigate the role of VDR gene polymorphisms in COVID-19 severity and outcome, a total of 292 COVID-19 patients were classified according to severity in moderate (n = 56), severe (n = 89) and critical (n = 147) and, according to outcome in survivor (n = 163) and deceased (n = 129), and analysed for FokI and TaqI VDR gene polymorphisms by polymerase chain reaction-based restriction enzyme digestion. The FokI and TaqI single nucleotide polymorphisms (SNPs) were not associated with COVID-19 severity or mortality individually but when analysed by haplotype, TC was associated with an increased risk of presenting critical COVID-19. Additionally, FokI CT genotype was more frequent in COVID-19 patients with hypertension, and T allele carriers presented higher aspartate aminotransferase levels. Our results suggest a relationship between VDR FokI and TaqI SNPs and COVID-19 severity in Mexican population. Although there are some previous reports of VDR polymorphisms in COVID-19, this represents the first report in Latin American population. Further studies on other populations are encouraged.

Signal transducer and activator of transcription 4 (STAT4) plays a crucial role in the host immune response against Mycobacterium tuberculosis. This study investigates the association between STAT4 gene polymorphisms and pulmonary tuberculosis (TB) risk in the Moldavian population. A total of 272 TB patients and 251 community-matched controls underwent screening for functional single-nucleotide polymorphisms (SNPs) rs897200 and rs7574865 in the STAT4 gene. The minor T allele and the TT/CT genotype of rs897200 demonstrated a significant association with reduced pulmonary TB risk (allelic model: adjusted OR = .74, p = .025; log-additive model: adjusted OR = .72, p = .02; and dominant model: adjusted OR = .65, p = .023), indicating a protective effect. Similar associations, characterized by an even more pronounced reduction in risk, were observed among females and late-onset TB patients (>44 years). No significant associations were found for rs7574865. In addition, a combined genotype analysis incorporating 43 SNPs from our previous studies revealed potential associations, such as STAT4 rs897200 CT with IFNG rs2430561 AA (adjusted OR = .36, p = .0025) and STAT4 rs897200 CT with TNFA rs1800629 GA (adjusted OR = .33, p = .0012). This study emphasizes the significant association of STAT4 rs897200 with pulmonary TB risk in the Moldavian population, underscoring its role in the disease development.

Despite recent advances that have improved outcomes following intestinal transplantation (ITx), achieving long-term patient survival and rejection-free survival is still challenging. Understanding the relevance of pre-transplant human leukocyte antigen (HLA) donor-specific antibody (DSA) in ITx and the immunomodulatory potential of the liver within the allograft is crucial to providing an accurate assessment of pre-transplant immunological risk, which could influence and improve post-transplant outcomes further. This was the primary objective of this retrospective study of 95 adult ITx transplants which took place at Cambridge University Hospitals (United Kingdom) between 2007 and 2019. Two novel programs were developed and validated to identify DSA (tested by Luminex single antigen beads) in this dataset. Data analysis utilised Kaplan–Meier survival methods, and statistical analysis was performed using log-rank tests and adjusted Cox models. Fifty-four (57%) ITx cases contained a liver, and 36 (38%) were sensitised to HLA. Pre-transplant DSA > 500 mean fluorescent intensity appeared to negatively affect post-ITx patient survival and rejection outcomes. Additionally, liver-inclusive allografts seemed to show particular resistance to HLA class I DSA. Our data hints towards consistency with other ITx studies where deleterious effects of DSA have been demonstrated, and where liver inclusion is protective from HLA class I DSA. This is in line with current national guidelines for immunological risk. Our publicly available research programs could support future large or multicentre studies where statistically relevant data might be gained.

We have read with great interest the recently published UK NEQAS and BSHI guideline on laboratory testing and clinical interpretation of HLA genotyping results supporting the diagnosis of coeliac disease (CD) by Pritchard et al. (2023). Interpretation of HLA genotyping for CD can be challenging in clinical practice, and sometimes even misleading, and these proposed guidelines provide a valuable framework for standardizing HLA genotyping and its interpretation in the context of CD diagnosis. However, we would like to address a particular point of contention regarding excluding CD in patients expressing only HLA-DQA1*05 (in the form of DQ7.5) in the absence of HLA-DQ2.5, DQ8 and DQ2.2.

The guideline suggests that the presence of DQA1*05 alone (which occurs in HLA-DQ7.5), without the corresponding DQB1*02 allele to form the DQ2.5 heterodimer in cis or trans, should lead to the exclusion of CD (Pritchard et al., 2023). However, in our experience, coeliac patients expressing only HLA-DQ7.5 do exist, and among coeliac patients diagnosed at our centre are roughly as common as those with only DQ8 or only DQ2.2. More precisely at our centre we have diagnosed 6 DQ7.5⁺, 6 DQ2.2⁺ and 4 DQ8⁺ coeliac patients. This may seem strange at first, but it might be explained by the very high frequency of the DQ7.5 haplotype in the Italian general population (26%), whereas DQ2.2 is less common (15%) and DQ8 is quite rare (2%) (Margaritte-Jeannin et al., 2004). These figures differ significantly from those of other populations, as data show a HLA-DQ7.5 prevalence of 17% in France (Margaritte-Jeannin et al., 2004), 11% in a European American population (Megiorni et al., 2009) and 10% in Scandinavia (Margaritte-Jeannin et al., 2004).

Data in the literature also show that a small, yet significant, subset of coeliac patients express only HLA-DQ7.5. More precisely, estimates show that 0.3%–2.1% of coeliac patients carry only the DQ7.5 allele in the absence of DQ2.5, DQ8 and DQ2.2 (Erlichster et al., 2020; Fernández-Bañares et al., 2017; Karell et al., 2003; Margaritte-Jeannin et al., 2004; Megiorni et al., 2009; Schiepatti et al., 2021; Tinto et al., 2015). Moreover, in a large multicentric study on seronegative CD, DQ7.5 alone was also found among seronegative patients (Schiepatti et al., 2021). Therefore, although the risk conferred by DQ7.5 alone is indeed very low, it is not negligible and we think that DQ7.5 alone may not ‘automatically’ exclude CD. The exclusion of CD based on DQ7.5 could therefore lead to missed diagnoses in a small minority of coeliac patients carrying only DQ7.5, who could otherwise benefit from a gluten-free diet and appropriate management of their condition.

Given the potential clinical implications, w

Chronic inflammation triggered by hepatitis B (HBV) and hepatitis C (HCV) viruses elevates interleukin 6 (IL-6) levels, activating pathways that cause liver damage and contribute to hepatocellular carcinoma (HCC) development. In this study, we assessed IL-6 levels and explored the correlation between the rs1800795 and rs1800797 variants of the IL-6 gene and the risk of developing HCC. We conducted a case–control study involving 314 participants. Among them, 157 were HCC patients (94 anti-HCV, 22 HBsAg and 41 metabolic dysfunction-associated steatotic liver disease [MASLD]) and 157 controls. Genotyping for IL-6 rs1800795 and rs1800797 polymorphisms was performed using real-time polymerase chain reaction (PCR). Additionally, plasma IL-6 levels were determined using enzyme-linked immunosorbent assay. The IL-6 levels were notably higher in patients compared to controls (p < .0001). Among HCC patients, those with MASLD exhibited higher plasma IL-6 levels than those with HCV and HBV (p = .003). In male HCC patients, IL-6 levels were significantly elevated compared to controls (p < .0001). Similarly, female patients showed significantly higher IL-6 levels compared to female controls, though still lower than in male HCC patients (p = .023). However, no significant difference was observed in IL-6 levels between male and female HCC patients (p = .129). Contrastingly, the genotype and allele distributions of the rs1800795 and rs1800797 polymorphisms in the IL-6 gene displayed no association with HCC development (all p > .05). In Moroccan HCC patients, chronic liver inflammation is characterized by elevated levels of IL-6, potentially playing a role in the progression of liver disease and tumourigenesis.

The autophagy gene immunity-related GTPase M (IRGM) can affect the immune response against intracellular pathogens. The study was performed to determine any possible association between three IRGM single-nucleotide polymorphisms (SNPs) (rs4958842, rs4958843 and rs4958846) and chronic hepatitis B virus (HBV) infection. A total of 171 chronic HBV-infected individuals and 171 healthy controls were collected. Peripheral blood cells and Sanger sequencing were used to extract genomic DNA and determine the SNP genotypes, respectively. The C allele of rs4958843 is a risk factor for chronic HBV infection in various genetic models, including allelic, codominant and dominant models, with the following respective statistical data: allelic (T vs. C: OR = 1.371, 95% CI = 1.009–1.863, p = .043), codominant (TT vs. CC: OR = 2.137, 95% CI = 1.104–4.138, p = .024) and dominant (TT + TC vs. CC: OR = 1.976, 95% CI = 1.106–3.533, p = .021) models. The genotype and allele distributions of rs4958842 and rs4958846 showed no significant differences between chronic HBV infection patients and healthy controls. IRGM rs4958843 CC genotype carriers had significantly elevated values of alanine transaminase, aspartate transaminase alpha-fetoprotein and total bilirubin (OR = 3.467, 95%CI = 1.167–10.298), which was positively associated with the disease progression of HBV infection. Mutant allele C of IRGM rs4958843 polymorphism is associated with the risk of chronic HBV infection in the Han people in central China and contributes to the disease progression.

STrengthening the REporting of Genetic Association (STREGA) studies strongly recommend that researchers assess the Hardy–Weinberg equilibrium (HWE) in their control groups. The exact frequency of studies in which their control subjects show a significant deviation from the HWE is not well established. Therefore, the present study was conducted. The electronic database PubMed was searched using the terms: ‘meta-analysis’ and ‘polymorphism’. Data of original articles were extracted from meta-analysis. The STREGA statement was published in 2009. Therefore, studies were divided into two groups, before and after the statement. After data collection, quartiles for sample size and minor allele frequency (MAF) were determined separately. A total of 772 independent studies were extracted from these meta-analyses and included in the current study. Multivariate analysis revealed the following associations: (1) Reports published after the STREGA statement (compared to before the statement) were associated with an increased prevalence of deviation from HWE. (2) Reports with sample size Q2–Q4 versus Q1 were associated with an increased prevalence of deviation from HWE. (3) Studies with MAF Q4 versus Q1 were negatively associated with the prevalence of reports of deviation from HWE. We conclude that the STREGA statement failed to change the attitudes and practices of researchers and editors towards the importance of HWE.

The demographic factors, the socioeconomic status and the ethnicity of populations are important players that determine the incidence, the prevalence and the spectrum of systemic lupus erythematosus (SLE) clinical presentations in different populations. Therefore, the purpose of the present research was to investigate the possible association between the Ikaros family zinc finger 1 gene (IKZF1) rs4132601 and rs11978267 single nucleotide polymorphisms (SNPs) and SLE susceptibility and clinical presentations including lupus nephritis (LN) among Egyptian paediatric patients. After DNA extraction from Ethylenediaminetetraacetic acid (EDTA) blood samples for 104 paediatric SLE (pSLE) patients and 286 healthy controls, the investigated SNPs (IKZF1 rs4132601 and rs11978267) were genotyped using TaqMan-Real-time Polymerase chain reaction (PCR). The G allele, GG and GT genotypes of IKZF1 rs4132601 were associated with pSLE (p_c<.001, OR 2.97, 3.2 and 2.25, respectively). The GG and GA haplotype were more frequent in pSLE patients than other haplotypes (p_c<.001, OR 3.47 and p_c = .004, OR = 2.8, respectively). The studied SNPs have no impact on the distinctive features of pSLE. The rs4132601 TG genotype was significantly associated with proliferative LN (p_c = .03) The IKZF1 rs4132601 can be considered a risk factor for SLE in the cohort of Egyptian children. The TG genotype of the IKZF1 rs4132601 may predispose to proliferative LN.