International Journal of Immunogenetics最新文献

Toll-like receptors (TLRs) induce the production of pro-inflammatory cytokines and regulate the immune response to Plasmodium vivax infection. Genetic variants of TLRs are associated with susceptibility and severity of malaria in different populations. This study aimed to evaluate the association between polymorphisms in TLR1, TLR4, TLR7, TLR8, TLR9 and TIRAP and the clinical manifestations of malaria caused by P. vivax in a population from the Amazon region of Pará, Brazil. A total of 148 individuals with symptomatic uncomplicated malaria were genotyped for rs4833095, rs1927911, rs179008, rs3764880, rs352140 and rs8177374 variants, and their associations with parasitaemia levels, gametocytaemia and clinical index were analysed using generalised linear models. TLR9 rs352140TT homozygotes had higher parasitaemia levels than C allele carriers (p = 0.034). TLR4 rs1927911GG homozygotes had a higher clinical index than A allele carriers (p = 0.018). Our results describe, for the first time, the association of the rs1927911 variant found in intron 1 of TLR4 with P. vivax malaria symptoms in Brazilian Amazonian population.

The highly polymorphic HLA genes inform susceptibility and resistance to infectious and autoimmune diseases and cancers and are key for successful solid-organ and stem-cell transplantation therapies. Over 41,000 HLA alleles are known and are unevenly distributed across the human population. Here, we describe HLAtools, Searching Shared HLA Amino-Acid Residue Prevalence (SSHAARP) and the Global Frequency Browser (GFB), new informatic tools developed to facilitate working with HLA data and visualizing the global distribution of HLA variants in human populations. HLAtools is an R package that consumes static resources for HLA alleles and sequences and makes these data locally computable alongside data-query, data-customization and data-analysis functions. The package further includes new reference datasets that dissect and catalogue HLA regions and HLA gene structures and provide insight into the organization of HLA pseudogenes and gene fragments. SSHAARP is an R package that describes the frequency distributions of individual HLA haplotypes, alleles and amino-acid motifs as global heatmaps. Allele frequency maps for more than 800 HLA alleles can be browsed using the GFB web and mobile applications. HLAtools and SSHAARP are available from the Comprehensive R Archive Network, and the GFB apps are available on GitHub.

Background: Acute lymphoblastic leukaemia (ALL) is characterized by the clonal proliferation of immature lymphoid precursors in the bone marrow or peripheral blood. This study investigates whether genetic polymorphisms in IL-17RC are associated with an increased risk of ALL in the Saudi population.

Methods: This case-control study included 95 patients with ALL and 95 matched controls. Genetic polymorphisms and their associations with ALL risk were identified using logistic regression analysis. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess the level of IL-17RC mRNA.

Results: The results revealed that carriers of the GA and AA genotypes of rs76999397 had a significantly increased risk of ALL (GA: odds ratios [OR] = 63.78, 95% confidence interval [CI] = 25.51–159.43, p < 0.0001; AA: OR = 18.22, 95% CI = 1.50–221.37, p < 0.0001). Additionally, we identified that an increased risk of ALL was associated with two haplotypes in IL-17RC, C-A and T-A (in the order of rs708567 and rs76999397) (OR = 46.73, 95% CI = 17.30–126.28; OR = 49.42, 95% CI = 6.95–351.45, respectively).

Conclusions: The results suggested that the GA and AA genotypes of rs76999397 were significantly associated with an increased risk of ALL, whereas rs708567 did not show a significant association. Furthermore, the CA and TA haplotypes (rs708567/rs76999397) were found to be associated with increased susceptibility to ALL.

IgA nephropathy (IgAN) is one of the most prevalent glomerulonephropathies and commonly leads to kidney failure. The recurrence of IgAN following transplantation remains a significant concern. Currently, detecting IgAN recurrence requires a kidney biopsy, highlighting the need for non-invasive biomarkers such as donor-derived cell-free DNA (dd-cfDNA) to aid in early detection. This prospective pilot study aims to evaluate dd-cfDNA as a non-invasive biomarker for detecting IgAN recurrence post–kidney transplantation. Specifically, the study seeks to compare %dd-cfDNA levels in transplanted patients with and without IgAN recurrence and correlate these levels with other kidney function parameters. A total of 32 patients with histologically confirmed IgAN were enrolled, including those with documented IgAN recurrence post-transplantation and those without recurrence. Plasma samples were collected and processed using the AlloSeq cfDNA kit to quantify relative %dd-cfDNA levels. Kidney function parameters, including estimated glomerular filtration rate (eGFR) and proteinuria, were also assessed. The study found no significant difference in %dd-cfDNA levels between transplanted patients with IgAN recurrence and those without recurrence (median 0.37% [IQR 0.28%–3.53%] vs. median 0.42% [IQR 0.15%–0.84%], p = 0.67). Also, %dd-cfDNA (AUC = 0.57 [95% CI 0.28–0.85], p = 0.64) failed to effectively discriminate IgAN recurrence compared to traditional kidney function parameters such as proteinuria (AUC = 0.96 [95% CI 0.87–1.00], p = 0.002) and eGFR (AUC = 0.74 [95% CI 0.47–1.00], p = 0.09). Relative (%) dd-cfDNA alone may not be a robust biomarker for detecting IgAN recurrence post-transplantation. While proteinuria proved a more effective indicator in this study, kidney biopsy remains the gold standard for definitive diagnosis. These findings highlight the challenges of using %dd-cfDNA as a standalone diagnostic tool for monitoring IgAN recurrence post-transplantation. Future research should explore larger patient cohorts and longitudinal assessments to refine the utility of dd-cfDNA and investigate potential combination strategies with other biomarkers.

Primary HIV-associated thrombocytopenia (PHAT) is an isolated thrombocytopenia in HIV-positive individuals in the absence of secondary causes. The presence of certain Human Leukocyte Antigens (HLA) has been linked to individuals’ immune response to HIV and the development of immune-mediated thrombocytopenic disorders. Considering the established associations between HLA and HIV infection and HLA and immune-mediated thrombocytopenias, we hypothesise that specific HLA alleles may also increase the risk of developing PHAT, a condition that links both HIV and immune-mediated thrombocytopenia. Therefore, the study aimed to determine the frequency of high-resolution HLA alleles in patients presenting with possible PHAT. Following a detailed screening process, we evaluated the HLA profiles of 43 participants with probable PHAT using the Axiom Precision Medicine Diversity Array (PMDA) Kit on the GeneTitan Multi-Channel instrument. No single HLA allele was found to be more prominent in our PHAT population. However, 93.02% of participants had both HIV-protective and HIV-susceptible alleles. The potential mechanism causing thrombocytopenia to be the only clinically relevant haematological abnormality in these patients remains to be explored. We concluded that the presence of both an HIV-protective and HIV-susceptibility allele in the same individual may cause antagonistic immune reactions, resulting in thrombocytopenia in HIV-positive individuals. We propose future long-term follow-up studies to determine the progression and outcome in patients with PHAT.