COVID-19 vaccination, both in healthy individuals and those with comorbid medical disorders, has proven highly effective in mitigating critical disease progression and mortality rates. Nevertheless, although rare, induction of autoantibodies and new-onset autoimmune conditions in apparently healthy individuals receiving COVID-19 vaccination have been documented. These autoimmune phenomena can be broadly classified into organ-specific autoimmune disorders (e.g., subacute thyroiditis (SAT)) and systemic autoimmune disorders, with many being generally transient (e.g., vaccine-induced thrombotic thrombocytopenia (VITT)) and others causing chronic disability (e.g., systemic vasculitis). Recent studies have highlighted significant associations between COVID-19 vaccine-associated autoimmunity and human leukocyte antigen (HLA) loci. For example, HLA class I alleles such as HLA-B*35 and HLA-C*04 have been associated with COVID-19 vaccine-induced SAT, while HLA class II alleles, including HLA-DRB1*11:04, HLA-DQA1*05:01, HLA-DQB1*02:01, and HLA-DPB1*17:01, have been linked to VITT. This review synthesizes the reported associations between classical HLA loci and COVID-19 vaccine-induced autoimmunity, providing insights into potential mechanisms and clinical implications.
BACKGROUND:Cholesteatoma recurrence is relatively common and often requires repeat surgical interventions, imposing a significant burden on patients and healthcare systems. Although clinical factors such as age, disease aggressiveness, surgical technique, and surgeon experience influence recurrence risk, accurate prediction remains challenging. Genetic Risk Scores (GRS), which aggregate the effects of multiple genetic variants, offer a promising approach to individualized recurrence risk estimation. OBJECTIVE:To evaluate the contribution of specific genetic variants to cholesteatoma recurrence by constructing a GRS using data from the UK Biobank. METHODS:A systematic review of PubMed identified six genes previously associated with cholesteatoma recurrence: KGF (FGF7), KGF-R (FGFR2), MMP9, KRT1, KRT10, and MIF. Corresponding single nucleotide polymorphisms (SNPs) were analyzed using the UK Biobank, a large-scale biomedical database of approximately 500,000 participants. Individuals with recurrent cholesteatoma were identified using ICD-10 code H95.0. SNPs with minor allele frequency <5% or in linkage disequilibrium were excluded. A weighted GRS was calculated by summing the number of risk alleles for each SNP, multiplied by their β coefficients (log odds ratios). RESULTS:A total of 39 SNPs were included in the final GRS calculation. Among 502,164 UK Biobank participants, 55 individuals were identified with recurrent cholesteatoma. The mean GRS for these individuals was 3.86, compared to 3.72 in the general population, indicating a 15.6% relative increase in genetically determined recurrence risk (OR ≈ 1.156). CONCLUSIONS:This study demonstrates a modest but measurable contribution of genetic variation to cholesteatoma recurrence. While the effect size is limited, future studies with larger cohorts and genome-wide data may improve predictive accuracy. Even at this stage, the GRS may help guide surgical decision-making and follow-up planning, moving toward more personalized management of cholesteatoma.
OBJECTIVES:Epstein-Barr virus (EBV) associated gastric cancer (EBVaGC) represents a distinct subtype of gastric carcinoma clinically characterized by low frequency of lymph node metastasis and better prognosis as compared to the EBV-negative gastric cancer (EBVnGC). Differential expression analysis of the transcriptome from tumor tissues revealed frequent involvement of immune genes which emphasizes the exclusive significance of immune response in EBVaGC patients. Considering the reported over-expression of toll-like receptor (TLR) genes in EBV infection and giving the crucial roles of TLRs in the innate immune system, we assumed that the entire TLR signaling pathway could have been differentially regulated in EBVaGC. METHODS:We tested our hypothesis by performing a differential expression analysis of the whole TLR signaling pathway using gene set enrichment test. RESULTS:A self-matched test detected a significant upregulation of the TLR signaling pathway in tumor as compared with non-tumor gastric tissues of EBVaGCs (P = 4×10-3) but no significant differential regulation of the pathway in EBVnGCs. A comparison of tumor gastric tissue in EBVaGCs versus non-tumor gastric tissue in EBVnGCs showed an even more significant upregulation of the pathway with a high enrichment of overexpressed genes (P = 2.5×10-4). CONCLUSIONS:Briefly, this study revealed a distinct pattern of activation of the TLR signaling pathway in EBVaGCs which can be seen as a specific feature of molecular pathology in the disease. This feature characterizes the disease as a distinct subtype of gastric cancer in oncogenesis which can be linked to its clinical manifestation and prognosis to motivate improved treatment strategies for both EBVaGC and EBVnGC patients.
Objectives: Women are at a significantly higher risk of osteoporotic fractures, largely due to progressive bone demineralization and impaired bone microarchitecture. Low bone mineral density (BMD) is a common condition in women worldwide. Disrupted homocysteine (Hcy) metabolism has been linked to reduced BMD and increased risk of osteoporotic fractures. Hyperhomocysteinemia (Hhcy) affects osteoblast and osteoclast activity, interferes with collagen cross-linking in the extracellular matrix, and has a detrimental effect on bone health. This study aimed to establish the association between hematological and biochemical parameters and osteoporosis in adult females. Methods: We measured Hcy, creatinine, uric acid (UA), vitamin B12, and vitamin D levels. Significantly elevated Hcy (27.322 ± 0.816 vs 10.152 ± 0.381 µmol/L), creatinine (0.670 ± 0.012 vs 0.587 ± 0.011 mg/dL), and UA (5.118 ± 0.083 vs 2.786 ± 0.060 mg/dL) were found in osteoporotic females, while reduced concentrations of vitamin B12 (148.883 ± 2.192 vs 294.14 ± 6.505 pg/mL) and vitamin D (24.98 ± 0.621 vs 33.7 ± 0.652 ng/mL) were observed. Results: Hematological parameters were found differentially expressed in osteoporotic females. Elevated Hcy levels, combined with reduced vitamin B12 and vitamin D, were strongly associated with decreased BMD and a higher susceptibility to osteoporotic fractures. Women with increased Hcy levels also had lower T-scores compared to those without Hhcy. Conclusions: These findings suggest that Hcy plays a critical role in bone resorption and osteoporotic fractures. Regulating Hcy metabolism may serve as an effective therapeutic strategy for managing bone resorption and osteoporosis. We hypothesize that elevated Hcy levels are closely related to low BMD and an increased risk of osteoporosis.
Artemisinin Combination Therapies (ACT) stand as the most potent antimalarial treatments. In response to the emergence of ACT-resistant malaria parasites in Southeast Asia, the World Health Organization (WHO) has recommended continuous monitoring of the effectiveness of ACT and other antimalarials. To address this need, we collected dried blood spots from malaria patients during a 42-days drug efficacy trial evaluating the efficacy of Artesunate plus Amodiaquine (ASAQ), Artemether Plus Lumefantrine (AL) and Dihydroarthemisinine plus Piperaquine (DHAPQ) on simple P. falciparum malaria in 2017. Blood samples were collected on Day 0, prior to the patients' initial ACT dose, and on any days of recurrent parasitemia. Genetic markers such as Merozoite Surface Protein 1 (MSP1) and Merozoite Surface Protein 2 (MSP2) were genotyped to differentiate between recrudescence and re-infestation cases. Furthermore, PCR Single Specific Oligonucleotide Probes combined with-ELISA platform (PCR-SSOP-ELISA) and PCR-RFLP techniques were used to identify Pfcrt 72-76 mutant haplotype and Pfmdr1_86Y allele associated with chloroquine and amodiaquine resistance, respectively. Out of the 320 patients enrolled in the study, only 43 (13.43%) experienced relapses. Upon PCR correction, our analysis revealed that recrudescent infections affected 13 patients, with 8 in the ASAQ group, 5 in the AL group, and none in the DHAPQ group. Notably, no early treatment failures (within the first 3 days of treatment) were observed, and all recurrences occurred between Day 21 and Day 42. The prevalence of the Pfcrt wild-type haplotype CVMNK and Pfmdr N86 allele was 67.03% and 97.70%, respectively. In contrast, the mutant types CVIET and 86Y were found at 32.97% and 2.3%, respectively. The high prevalence of the CVMNK wild haplotype suggests that the parasites remain sensitive to chloroquine, while the low prevalence of the 86Y mutants indicates continued effectiveness of amodiaquine. Furthermore, the low prevalence of strains exhibiting the combination of CVIET and 86Y suggests that the use of multiple antimalarials is valuable for resistance control. Notably, none of the relapse cases carried the 86Y mutation or the combination of 86Y and CVIET.
