International Journal of Immunogenetics最新文献

Vitamin D deficiency is widespread and poses a significant health concern, as emerging research links it to allergic diseases owing to its immunomodulatory functions. The optimal functioning of vitamin D and its activation depend on its nuclear receptor, vitamin D receptor (VDR). Genetic variants of VDR have been explored as potential factors in autoimmune and allergic diseases, with limited studies on their association with allergic rhinitis (AR). The present investigation aims to analyse the role of three VDR genetic variants – TaqI, FokI and BsmI – in AR susceptibility and their impact on VDR mRNA and serum vitamin D levels. A total of 550 subjects, consisting of 250 AR cases and 300 age- and gender-matched controls, underwent genotyping by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). VDR mRNA and vitamin D levels were determined by quantitative real-time PCR and chemiluminescence, respectively. Although TaqI did not exhibit significant differences, FokI demonstrated a noteworthy association with AR, particularly with the CC genotype (odds ratio [OR]: 3.34; confidence interval [CI]: 1.79–6.23). Similarly, BsmI revealed an increased risk for AR, with the GA + AA genotypes showing a 2.2-fold elevated risk (OR: 2.20; CI: 1.53–3.16). VDR mRNA expression was threefold lower in AR patients (p < .0001), accompanied by reduced serum vitamin D levels (p < .0001). In addition, CC (p = .01) and AA (p = .02) genotypes of FokI and BsmI were associated with reduced VDR mRNA levels, whereas TaqI showed no such association. Similarly, heterozygous genotypes of TaqI and FokI, as well as homozygous AA of BsmI, correlated with lower serum vitamin D levels (p < .001). This study emphasizes the intricate relationship among VDR genetic variations, altered VDR activity, immune modulation and vitamin D metabolism in AR. Further research involving diverse populations is crucial for confirming and generalizing these findings, paving the way for personalized therapeutic interventions in vitamin D–related disorders.

Penicillin allergy is a potentially life-threatening condition that is common among patients. However, the genetic associations with penicillin allergy are not yet recognized for prevention or diagnosis, particularly in East Asian populations. We conducted a retrospective case–control study using data from the Taiwan Precision Medicine Initiative and analysing DNA samples to identify eight major MHC Class I and Class II loci. We employed imputation methods for accurate HLA typing and enrolled 17,827 individuals who received penicillin. Logistic regression analyses were utilized to explore associations between HLA genotypes, comorbidities and allergy risk, while simultaneously conducting a subgroup analysis to explore the association between HLA genotypes, comorbidities and the severity of allergic reactions. Our study assigned 496 cases to the penicillin allergy group and 4960 controls to a matched group. The risk of penicillin allergy was significantly higher with HLA-DPB1*05:01 (OR = 1.36, p = .004) and HLA-DQB1*05:01 (OR = 1.54, p = .03), with adjusted p-values of .032 and .24, respectively. Urticaria was identified as a separate risk factor (OR = 1.73, p < .001). However, neither the HLA alleles nor the comorbidities had a significant relationship with the risk of severe penicillin-induced allergy. HLA-DPB1*05:01 was found to be significantly associated with penicillin allergy reactions among the Taiwanese population.

The purpose of this review is to encourage a new perspective on the question of donor–recipient compatibility and post-transplant assessment of graft health based on functional measures. The premise is that we should be better sighted on what (and how) the immune system responds toward rather than what is merely there. Continuance of the pursuit of further and better definition of antigens and antibodies is not however discouraged but seen as necessary to improved understanding of the structural correlates of functional immunity. There currently exists, in the opinion of the authors, an opportunity for histocompatibility and immunogenetics laboratories to develop and widen their scope of involvement into these new areas of laboratory activity in support and to the benefit of the transplant programmes they serve.

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.