Human Immunology[JOURNAL]
Sun
200 papers
Nine neutrophil enzyme pathways can initiate hyperinflammatory or autoimmune diseases.
Roe K
Hum Immunol · 2025 Jul · PMID 40651068 · Publisher ↗
There is substantial experimental evidence suggesting several autoimmune or hyperinflammatory diseases, including multisystem inflammatory syndrome and Kawasaki disease, can be initiated by at least nine neutrophil enzym...
There is substantial experimental evidence suggesting several autoimmune or hyperinflammatory diseases, including multisystem inflammatory syndrome and Kawasaki disease, can be initiated by at least nine neutrophil enzyme pathways. One pathway can also be facilitated by lymphocyte suppression or exhaustion by a virulent pathogen, but eight pathways involving subtypes of neutrophil extracellular traps, are independent from lymphocyte suppression or exhaustion by a pathogen. All nine pathways involve activated neutrophils. In the first pathway, abnormally high releases of proteases from neutrophils and other immune cells respond to certain pathogen infections, and can expose auto-antigens to initiate auto-reactive T cells or antibodies. In eight pathways, immune cells including neutrophils can respond to pathogens by undergoing one of eight different subtypes of NETosis, which will release enzymes causing a posttranslational removal of amine groups (citrullination) from nuclear histones which include positively charged arginine amino acid residues. The enzyme peptidyl arginine deaminase 4 is a major catalytic enzyme released from neutrophils and its catalytic reaction produces ammonium ions and neutral citrulline amino acid residues in histones and other proteins. The citrullinated host proteins can act as auto-antigens to the immune system, causing auto-reactive T cells or antibodies. The trigger for any of these nine neutrophil enzyme pathways can be a novel virulent infection, or possibly a reactivated latent pathogen.
A reappraisal of the contribution of Th9 cells and interleukin-9 to the pathogenesis of rheumatoid arthritis.
Jafarzadeh A, Khorramdelazad H, Jafarzadeh Z … +1 more , Nemati M
Hum Immunol · 2025 Jul · PMID 40639065 · Publisher ↗
Interleukin-9 (IL-9), the principal cytokine of Th9 cells, influences a vast range of functions due to the widespread expression of its receptor on various immune and non-immune cell types. Th9 cells and IL-9 play a detr...
Interleukin-9 (IL-9), the principal cytokine of Th9 cells, influences a vast range of functions due to the widespread expression of its receptor on various immune and non-immune cell types. Th9 cells and IL-9 play a detrimental role in the pathogenesis of some autoimmune diseases, such as rheumatoid arthritis (RA). Elevated Th9 cell numbers and higher IL-9 levels were observed in the peripheral blood and synovial tissues of patients with RA and animals with collagen-induced arthritis (CIA), correlating with disease activity. IL-9 can contribute to the pathogenesis of RA through multiple mechanisms, such as promoting the expansion and survival of pathogenic T cells; impairing the activity of regulatory T (Treg) cells; boosting the pathogenic responses of Th1 and Th17 cells; prolonging the survival and increasing the activity of synovial neutrophils; supporting the differentiation and activation of osteoclasts; enhancing the proliferation and survival of fibroblast-like synoviocytes (FLS); inducing the secretion of pro-inflammatory mediators from FLS; facilitating the polarization of pro-inflammatory M1 macrophages; and promoting the expansion of Th9 cells. Experimental and clinical evidence suggests that targeting IL-9/IL-9R and Th9 cells may be a promising approach for RA treatment. In addition, treatment with mesenchymal stem cells and various therapeutic agents showed beneficial effects in RA by downregulating inflammatory responses, such as Th9 cells and IL-9. This review provides a comprehensive explanation regarding the role of Th9 cells/IL-9 in RA pathogenesis and potential therapeutic approaches based on experimental and clinical findings.
Elevated regulatory T cells in pediatric patients recovering from multisystem inflammatory syndrome (MIS-C) are evident five months post-COVID-19.
Silva-Avelar I, Santos-Silva BD, Zheng Y … +15 more , Ferreira AEF, Gonçalves GS, Bain V, Matsuo OM, Martins F, Suguita P, Fink TT, Yoshino de Paula CS, Ferreira JCOA, da Silva CAA, Carneiro-Sampaio M, Marques HHS, Pereira MFB, Palmeira P, Corrêa-Silva S
Hum Immunol · 2025 Jul · PMID 40617227 · Publisher ↗
BACKGROUND: Children can present a severe post-COVID-19 condition called Multisystem Inflammatory Syndrome in Children (MIS-C) and regulatory T cells (Tregs) can regulate the immune response during the inflammatory proce...
BACKGROUND: Children can present a severe post-COVID-19 condition called Multisystem Inflammatory Syndrome in Children (MIS-C) and regulatory T cells (Tregs) can regulate the immune response during the inflammatory process, serving as an important tool for controlling the immune response. OBJECTIVE: To analyze the profile of Tregs in pediatric patients recovering from COVID-19 at two time points: between 2 and 8 months post-infection (visit 1) and between 10 and 15 months post-infection (visit 2). METHODS: This prospective cohort study included a convenience sample divided into two groups: CV1 (COVID-19, n = 67) and MV1 (MIS-C convalescents, n = 9) at visit 1, and CV2 (n = 42) and MV2 (n = 8) at visit 2. Participants were previously healthy or had pre-existing chronic conditions, diagnosed with COVID-19 between 2020 and 2021, unvaccinated, aged 2-18 years, and had confirmed SARS-CoV-2 infection. A control group of 70 individuals without COVID-19 was included using the same criteria. Treg cell phenotypes and cytokines (IL-6, IL-8, IL-12, IL-1β, TNF-α, IL-10) were analyzed using flow cytometry, and TGF-β by ELISA. RESULTS: The study found that the COVID-19 (CV1, CV2) and control (Ct) groups were matched by age, sex, and comorbidities, while the MIS-C groups (MV1, MV2) mostly included previously healthy individuals. Both CV1 and MV1 groups had reduced levels of IL-1β, IL-8, IL-12, and TNF-α, which normalized by visit 2, indicating a gradual recovery from the temporary immunosuppressive state. The MV1 group had higher Treg cell numbers, including CD45RA and CTLA-4 subpopulations, compared to the CV1 group. CD45RA expression was lower in CV1 and MV1, but the Foxp3/CD45RA ratio was significantly higher in CV1 compared to the controls and lower in MV2 compared to MV1 and CV2. MV1 also had higher Treg counts compared to healthy and immunosuppressed individuals from both the CV1 and control groups. CONCLUSION: Children recovering from COVID-19 showed changes in regulatory T cell populations associated with disease severity. Those who developed MIS-C had higher Treg cell counts and a temporary immunosuppressive state that persisted in the early convalescence period, normalizing around a year after infection.
Gene expression profile of immune response markers associated with long COVID and its clinical aspects in a cohort from northern Brazil.
Soares Pereira LM, de Souza E Souza I, Dos Santos Brito WR … +26 more , Dos Santos EF, da Costa FP, Lima de Sarges KM, Damasceno Cantanhede MH, de Brito MTFM, da Silva ALS, de Meira Leite M, de Almeida Viana MNDS, Barbosa Rodrigues FB, da Silva R, Rachid Viana GM, do Socorro Souza Chaves T, de Oliveira Lameira Veríssimo A, da Silva Carvalho M, Henriques DF, da Silva CP, Lima Nunes JA, Costa IB, Vieira Cayres-Vallinoto IM, Brasil-Costa I, Simões Quaresma JA, Monteiro Rangel da Silva AN, Freitas Queiroz MA, Dos Santos EJM, Magno Falcão LF, Rosário Vallinoto AC
Hum Immunol · 2025 Jul · PMID 40614661 · Publisher ↗
BACKGROUND: Long COVID is characterized by a multisystemic, and complex disease and current efforts are focused on the search for biomarkers associated with clinical outcomes. OBJECTIVE: In this study, we evaluated the g...
BACKGROUND: Long COVID is characterized by a multisystemic, and complex disease and current efforts are focused on the search for biomarkers associated with clinical outcomes. OBJECTIVE: In this study, we evaluated the gene expression of 15 biomarkers and their relationship with the clinical aspects of the condition. METHODS: c-DNA samples from 15 patients with long COVID, 15 patients recovered and without sequelae (RWS), and 15 patients with symptomatic acute COVID-19 were analyzed. The relative expression of genes was determined by the 2-ΔΔCT method from real-time PCR. Sociodemographic and clinical data of interest were extracted from medical records. RESULTS: Of the 15 biomarkers, only the expression of TREX1, FOXP3, MYD88 and FASL was not associated with long COVID. The genes IRF7, IRF3, and IFI16 performed best as biomarkers of long COVID (AUC ≥ 0.90, p ≤ 0.05). Except for MDA5 and RIG-1 genes, the expression of the other eight genes was associated with the presence of comorbidities, medication use, and complaints of fever, abdominal pain, eye pain, and headache (H > 9.0; p ≤ 0.05). IRF3 expression was specifically associated with long COVID when compared to acute COVID (med.: 41.2; IQR: 116.20; p: 0.0036). CONCLUSION: Our results suggest that classical immune response genes are upregulated in long COVID and that certain clinical aspects of the disease may influence the expression profile of the studied genes.
Human leukocyte antigen and its association with oral potentially malignant disorders - A systematic review and meta-analysis.
Purohit BM, Kanga U, Singh A … +1 more , Priya H
Hum Immunol · 2025 Jul · PMID 40554141 · Publisher ↗
BACKGROUND: The Human Leukocyte Antigen (HLA) genes, located within the Major Histocompatibility Complex on chromosome 6p21, are highly polymorphic and play a vital role in immunity and has strong associations with autoi...
BACKGROUND: The Human Leukocyte Antigen (HLA) genes, located within the Major Histocompatibility Complex on chromosome 6p21, are highly polymorphic and play a vital role in immunity and has strong associations with autoimmune disorders. However, its role in cancers including oral cancers and oral potentially malignant disorders (OPMD) is still being explored and there is no strong evidence available for this association. Hence the present systematic review was performed to synthesize the current available evidence of genetic propensity of HLA alleles in protective or susceptibility role in occurrence of OPMD. METHODS: A thorough search was conducted in Medline, PubMed, Cochrane, Scopus, Web of Science, EMBASE databases for relevant articles until June 2024. PRISMA guidelines were followed for conducting the systematic review. Of the nine studies selected for review, five evaluated the association of HLA with Lichen Planus, three studies were conducted in oral submucous fibrosis (OSF) patients and remaining one study dealt with all oral lesions including OPMDs. A total of 6493 participants from 9 studies were eligible for the systematic review, HLA association was compared between 757 diagnosed patients of OPMD and 5736 control group. The risk of bias was assessed using the Newcastle-Ottawa tool, with most of the studies indicating fair to good quality. RESULTS: Studies across varied ethnic groups showed that HLA-DR2 and HLA-DR6 antigen group which includes DRB1*14 alleles were observed more frequently in oral lichen planus while HLA-B7, HLA-A10 and HLA-DR3 were reported to be associated with oral submucous fibrosis. CONCLUSION: Certain HLA alleles have more predilection towards occurrence of oral premalignant disorders. Hence, future multiethnic large scale population studies are recommended to understand the molecular mechanism behind the occurrence OPMD, so that HLA can be developed as potential biomarker in diagnosis and/or treatment of OPMD.
Exploring associations of single nucleotide polymorphisms in ERAP1 and ERAP2 with susceptibility to multiple immune-mediated inflammatory diseases.
Jørgensen S, Bertelsen T, Kronborg L … +6 more , Dige A, Laurberg TB, Loft AG, Agnholt J, Hjuler KF, Johansen C
Hum Immunol · 2025 Jul · PMID 40543396 · Publisher ↗
Single nucleotide polymorphisms (SNPs) in the endoplasmic reticulum aminopeptidase 1 (ERAP1) and ERAP2 genes have been associated with susceptibility to various immune-mediated inflammatory diseases (IMIDs). We utilized...
Single nucleotide polymorphisms (SNPs) in the endoplasmic reticulum aminopeptidase 1 (ERAP1) and ERAP2 genes have been associated with susceptibility to various immune-mediated inflammatory diseases (IMIDs). We utilized a unique cohort from the National Centre for Autoimmune Diseases (NCAS) to investigate whether specific SNPs in ERAP1 and ERAP2 act as a shared genetic susceptibility factor across various IMIDs. The study population comprised 171 patients from the NCAS cohort with two or more IMIDs and 57 healthy controls. Using real-time PCR allelic discrimination methods, we genotyped specific SNPs in ERAP1 (rs30187, rs27524), ERAP2 (rs2248374) and HLA-C (rs4406273). The distribution of ERAP1 and ERAP2 risk/minor alleles, genotypes and haplotypes was similar in the NCAS cohort and in healthy controls. When stratifying for HLA-C*06:02 positive psoriasis patients, a disease-associated haplotype A-A-T (rs2248374, rs27524, rs30187) was identified, significantly increasing the odds for having psoriasis and one or more IMIDs (OR = 3.41, 95 % CI: 1.32 - 8.78, p = 0.008). While SNPs in ERAP1 and ERAP2 may not constitute a shared susceptibility factor across all IMIDs, this study suggests a complex interaction between HLA types, ERAP1, and ERAP2, potentially influencing the development of certain MHC-I-associated disorders.
Precision medicine and machine learning to predict critical disease and death due to Coronavirus disease 2019 (COVID-19).
Júnior WLDT, Danelli T, Tano ZN … +12 more , Cassela PLCS, Trigo GL, Cardoso KM, Loni LP, Ahrens TM, Espinosa BR, Fernandes AJ, Almeida ERD, Lozovoy MAB, Reiche EMV, Maes M, Simão ANC
Hum Immunol · 2025 Jul · PMID 40527075 · Publisher ↗
INTRODUCTION: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19) and induces activation of inflammatory pathways, including the inflammasome. OBJECTIVE: The aim wa...
INTRODUCTION: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19) and induces activation of inflammatory pathways, including the inflammasome. OBJECTIVE: The aim was to construct Machine Learning (ML) models to predict critical disease and death in patients with COVID-19. METHODS: A total of 528 individuals with SARS-CoV-2 infection were included, comprising 308 with critical and 220 with non-critical COVID-19. The ML models included imaging, demographic, inflammatory biomarkers, NLRP3 (rs10754558 and rs10157379) and IL18 (rs360717 and rs187238) inflammasome variants. RESULTS: Individuals with critical COVID-19 were older, higher male/female ratio, body mass index (BMI), rate of type 2 diabetes mellitus (T2DM), hypertension, inflammatory biomarkers, need of orotracheal intubation, intensive care unit admission, incidence of death, and sickness symptom complex (SSC) scores and lower peripheral oxygen saturation (SpO) compared to those with non-critical disease. We found that 49.5 % of the variance in the severity of critical COVID-19 was explained by SpO and SSC (negatively associated), chest computed tomography alterations (CCTA), inflammatory biomarkers, severe acute respiratory syndrome (SARS), BMI, T2DM, and age (positively associated). In this model, the NLRP3/IL18 variants showed indirect effects on critical COVID-19 that were mediated by inflammatory biomarkers, SARS, and SSC. Neural network models yielded a prediction of critical disease and death due to COVID-19 with an area under the receiving operating characteristic curve of 0.930 and 0.927, respectively. CONCLUSION: These ML methods increase the accuracy of predicting severity, critical illness, and mortality caused by COVID-19 and show that the genetic variants contribute to the predictive power of the ML models.
Pro inflammatory IL-1β: A potential biomarker for chronic chikungunya arthritis condition.
Thanapati S, Kulkarni S, Shinde T … +4 more , Ganu M, Ganu A, Jayawant P, Tripathy AS
Hum Immunol · 2025 Jul · PMID 40527074 · Publisher ↗
BACKGROUND: Cytokines and chemokines play a crucial role in orchestrating the immune response to chikungunya virus (CHIKV) infection, influencing disease course and outcome. Although significant efforts have been made to...
BACKGROUND: Cytokines and chemokines play a crucial role in orchestrating the immune response to chikungunya virus (CHIKV) infection, influencing disease course and outcome. Although significant efforts have been made to understand the cytokine signatures associated with CHIKV infection, the identification of specific cytokine biomarkers across different disease stages remains incomplete. MATERIAL AND METHOD: We have assessed CHIKV-specific cytokine, chemokine profiles of 17 analytes in 50 acute chikungunya patients, 31 chronic chikungunya arthritis patients, 30 recovered individuals, and 23 healthy controls. The cytokine and chemokines were measured in the supernatant of PBMCs stimulated in vitro with inactivated chikungunya virus. RESULTS: It was observed that chronic chikungunya arthritis patients exhibited significantly higher levels of IL-1β, IL-6, and GM-CSF compared to all other groups. MCP-1 levels were elevated in patient groups compared to recovered and control individuals. IL-1β emerged as a potential biomarker for chronic chikungunya arthritis based on ROC analysis. A negative correlation between IFN-γ levels and CHIKV load was observed in acute patients, suggesting its antiviral role. IL-12 levels were higher in recovered individuals compared to all other groups, while IFN-γ levels were elevated in recovered individuals compared to acute patients. CONCLUSION: Our findings highlight IL-1β as a potential biomarker for chronic chikungunya arthritis and suggest that GM-CSF inhibition could serve as a therapeutic intervention for disease-associated chronic inflammation. The observed co-regulation of IL-12 and IFN-γ in recovered individuals needs further investigation into their role in disease resolution. These insights provide a deeper understanding of the immunopathogenesis of CHIKV infection and may contribute in future diagnostic and therapeutic strategies.
Mast cells in autoimmune disease: Unveiling their multifaceted roles and therapeutic potential.
Javan MR, Akhlaghi M, Hormozi A … +2 more , Hosseini M, Khosrojerdi A
Hum Immunol · 2025 Jul · PMID 40479837 · Publisher ↗
Mast cells play a crucial role in developing autoimmune diseases by influencing immune responses, contributing to inflammation, and disrupting immune tolerance. This review examines the involvement of mast cells in vario...
Mast cells play a crucial role in developing autoimmune diseases by influencing immune responses, contributing to inflammation, and disrupting immune tolerance. This review examines the involvement of mast cells in various autoimmune disorders, including multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and type 1 diabetes mellitus (T1DM). The mechanisms through which mast cells mediate immune dysregulation are explored, focusing on their release of cytokines, role in antigen presentation, and interactions with other immune cells. Additionally, we discuss emerging therapeutic strategies aimed at targeting mast cells, such as monoclonal antibodies, small molecules, and inhibitors of signaling pathways, as potential approaches to modifying disease progression. Although the exact triggers and activation mechanisms of mast cells in autoimmunity are not yet fully understood, there is growing evidence suggesting that they may serve as valuable therapeutic targets. Further research is needed to refine therapies that focus on mast cells, enhance non-invasive detection methods, and optimize treatment strategies. Understanding the complex role of mast cells in autoimmune diseases could lead to innovative interventions aimed at reducing disease severity and improving patient outcomes.
Genetic polymorphism contributes to efficacy and adverse reactions of tenofovir combination lamivudine-based highly active antiretroviral therapy in HIV-infected patients.
Zeng L, Liu J, Xiong Y … +4 more , Ren H, Li C, Tang X, Li Z
Hum Immunol · 2025 Jul · PMID 40466234 · Publisher ↗
BACKGROUND: High HIV/AIDS prevalence in China calls for personalized therapies like pharmacogenomics to improve antiretroviral treatment efficacy. This study explored associations between single nucleotide polymorphisms...
BACKGROUND: High HIV/AIDS prevalence in China calls for personalized therapies like pharmacogenomics to improve antiretroviral treatment efficacy. This study explored associations between single nucleotide polymorphisms (SNPs) and outcomes of highly active antiretroviral therapy (HAART) in HIV-1 patients. METHODS: We collected blood samples and clinical data from 503 HIV-1-infected patients undergoing HAART for 12 months. Using bioinformatics databases, we identified 81 SNPs in genes related to drug transport, immunity, and HIV infection. These SNPs were genotyped and correlated with highly active antiretroviral therapy efficacy and side effects using the Mass Array system and SPSS. FDR multiple correction was performed on all positive SNPs. RESULTS: After 12 months of highly active antiretroviral therapy with Tenofovir disoproxil fumarate (TDF) and Lamivudine (3TC), the patients showed significant viral suppression and immune recovery.CD4 response was associated with GABPB1 rs12594956 (OR = 0.378, P = 0.002, FDR-P = 0.032). Viral load response was associated with CCR5 rs2734648 (OR = 22.812, P = 0.018, FDR-P = 0.045), IL2RA rs1323657 (OR = 18.312, P = 0.020, FDR-P = 0.045) and IL2 rs2069772(OR = 139.173, P = 0.002, FDR-P = 0.02). Rash risk was elevated with SLC22A2 rs316009 (OR = 16.077, P = 0.013, FDR-P = 0.048) and NRF2 rs1806649 (OR = 35.328, P = 0.002, FDR-P = 0.011). Liver toxicity was associated with SLC22A2 rs316009 (OR = 10.057, P = 0.005, FDR-P = 0.030). IFNL3 rs4803219 (OR = 2.461, P = 0.008, FDR-P = 0.024) and NRF1 rs11557288 (OR = 2.106, P = 0.035, FDR-P = 0.035) were linked to syphilis co-infection. NRF1 rs6949152 (OR = 0.329, P = 0.002, FDR-P = 0.030) were associated with HBsAg positivity in HBV co-infection.These results were verified in dominant or recessive models. CONCLUSION: This study establishes a foundation for using SNPs as predictive biomarkers for highly active antiretroviral therapy outcomes in Chinese HIV/AIDS patients, offering insights into personalized treatment strategies.
NEK7-mediated activation of NLRP1 and NLRP3 inflammasomes in the progression of Gestational Diabetes Mellitus.
Milan KL, Nandhana N, Shree RA … +4 more , Leela R, Jahnavi S, Anuradha M, Ramkumar KM
Hum Immunol · 2025 Jul · PMID 40435843 · Publisher ↗
Gestational Diabetes Mellitus (GDM) is characterized by impaired glucose metabolism and insulin resistance affecting up to 14.7 % of pregnancies. GDM is associated with adverse perinatal outcomes and long-term health ris...
Gestational Diabetes Mellitus (GDM) is characterized by impaired glucose metabolism and insulin resistance affecting up to 14.7 % of pregnancies. GDM is associated with adverse perinatal outcomes and long-term health risks for the offspring, including obesity and type 2 diabetes (T2DM). Maternal inflammation plays a key role in driving these complications, aggravating metabolic disturbances, and contributing to adverse developmental programming. In recent years, inflammasomes have emerged as the key regulators of inflammation. This study hypothesizes that NEK7 activates the inflammasomes in GDM pathogenesis. PCR analysis revealed that NEK7 expression, along with NLRP1 and NLRP3, was significantly overexpressed in pregnant women with GDM (n = 20) when compared to healthy pregnant women (n = 20). Further, a positive correlation was observed between NEK7 and the expression of NLRP1 and NLRP3, suggesting a potential mechanistic link in the regulation of inflammation in GDM. Additionally, the expression levels of NLRP1 and NLRP3 were found to strongly correlate with BMI, fasting glucose, postprandial glucose, HOMA-IR, and HbA1c levels in GDM patients. Furthermore, inflammatory cytokines, including IL-1β, IL-18, IL-6, and TNF-α, were significantly upregulated in GDM patients and positively correlated with the expression, suggesting the regulation of inflammation through inflammasomes. To validate the hypothesis, BeWo cells were cultured in a hyperglycemic environment. The results demonstrated that NEK7, along with inflammasomes and inflammatory cytokines, were significantly overexpressed in BeWo cells exposed to high glucose. Collectively, this study suggests that NEK7 upregulation may trigger inflammasome activation, contributing to the pathogenesis of GDM. These findings highlight the need for further research to develop the therapeutic approaches that target NEK7 to mitigate inflammation in GDM.
The effects of SARS-CoV-2 vaccines on antinuclear autoantibody formation in individuals without prior COVID-19 infection.
Dişli F, Yılmaz Y, Yıldız S
Hum Immunol · 2025 Jul · PMID 40424949 · Publisher ↗
BACKGROUND: Viral particles in SARS-CoV-2 vaccines have molecular motifs resembling self-antigens, potentially triggering autoantibody production. This study aimed to investigate the effects of mRNA vaccines (BioNTech),...
BACKGROUND: Viral particles in SARS-CoV-2 vaccines have molecular motifs resembling self-antigens, potentially triggering autoantibody production. This study aimed to investigate the effects of mRNA vaccines (BioNTech), which contain a single viral particle, and inactivated whole viral particles (Sinovac) on antinuclear autoantibody (ANA) formation in individuals without prior COVID-19 infection. MATERIAL AND METHODS: The study was retrospective and included individuals who had not contracted SARS-CoV-2 (tested negative for antigen or antibody). The effects of the inactivated vaccine were assessed in individuals with samples before and after both doses (n = 36); the mRNA vaccine was evaluated in individuals unvaccinated and after two doses (n = 17); and the effects of both vaccines were assessed in individuals who received only the inactivated vaccine (n = 15), only the mRNA vaccine (n = 15), or both (n = 15). ANAs were determined using validated anti-dsDNA, anti-ENA, and anti-Hep-2 nucleus tests. RESULTS: The inactivated vaccines cumulatively increased (p < 0.05) positivity for anti-dsDNA (from 13.9 to 36.1%) and anti-Hep-2 nuclear antibody (from 13.9 to 38.9%) but not anti-ENA antibodies (from 11.1 to 22.2%). The mRNA vaccine did not affect ANA formation compared to unvaccinated stages (p > 0.05). On the other hand, combination of both vaccine types increased the rate of positivity for the anti-dsDNA antibody (from 20.0 to 53.3%, p < 0.05). CONCLUSIONS: Small, yet valuable, sample size suggest that whole molecule vaccines may increase likelihood of ANA formation, probably due to exposure to increased number of assorted viral epitopes. Moreover, combination of both vaccines appears to increase anti-dsDNA antibodies and this deserves further investigation.
Expression variation of Akt and cytokines in lamivudine-resistant HBV rare mutation that prematurely truncates the overlapping surface protein.
Khan S, Anwer A, Sevak JK … +6 more , Abbas Z, Fatima K, Islam M, Jehan T, Trehanpati N, Kazim SN
Hum Immunol · 2025 Jul · PMID 40382902 · Publisher ↗
The sW196*(Stop) mutation of HBV is the rarest variant of sW196L. It is associated with rapid progression of chronic hepatitis B to end-stage liver disease and hepatocellular carcinoma. Information on proliferative vs. a...
The sW196*(Stop) mutation of HBV is the rarest variant of sW196L. It is associated with rapid progression of chronic hepatitis B to end-stage liver disease and hepatocellular carcinoma. Information on proliferative vs. apoptotic cells and immunological manifestations related to the expression of HBV-associated cytokines in the presence of the lamivudine-resistant mutation sW196L and the rarest variant of sW196L, sW196*(Stop), has been limited. Therefore, the current investigation aimed to examine the molecular and immunological basis of lamivudine-resistant mutations with the help of transfection studies carried out in cell lines of hepatic origin. sW196*(Stop) transfected HepG2 cells showed IFN-gamma was extremely downregulated by 20.96 folds, and IL-6 was upregulated by 4.5 folds which had not been seen in any of the constructs. The current study reveals for the first time the underlying immunological processes that render detrimental effects to lamivudine-resistant rare mutations, in particular sW196*(Stop) of HBV that can be explained by downregulation of IFN-gamma, a known cytokine associated with efficient viral clearance, together with upregulation of IL-6 known to be associated with disease progression and HCC. Understanding the molecular and immunological mechanisms in such HBV mutations is furthered by the choreographed event of increased TNF-alpha expression, which is known to be linked to liver damage.
A multilevel study on the genetic relationship between schizophrenia and inflammatory bowel disease.
Li C, Xu X, Luo Q … +5 more , Yang J, Shen P, Yuan X, Zhang X, Zhang L
Hum Immunol · 2025 Jul · PMID 40373620 · Publisher ↗
BACKGROUND: Schizophrenia (SCZ) and Inflammatory Bowel Disease (IBD) represent significant clinical challenges, frequently co-morbid and potentially linked by a genetic correlation. However, the precise mechanism underly...
BACKGROUND: Schizophrenia (SCZ) and Inflammatory Bowel Disease (IBD) represent significant clinical challenges, frequently co-morbid and potentially linked by a genetic correlation. However, the precise mechanism underlying this correlation remains elusive. METHODS: we utilized genome-wide association study (GWAS) data for SCZ and IBD to evaluate their genetic correlation. Initially, we performed an overall assessment using Linkage Disequilibrium Score Regression (LDSC), Genetic Covariance Analysis (GNOVA), and High-Dimensional Likelihood (HDL) methods. Subsequently, we conducted a more detailed local analysis using the Local Analysis of Variant Association (LAVA) method. To quantify the genetic overlap between these traits, we employed the Conditional/Joint False Discovery Rate (cond/conjFDR) statistical framework. Finally, by integrating the conjFDR analysis with Multi-Trait GWAS (MTAG), we successfully identified multiple shared genetic loci, shedding light on the genetic intersection between these two traits. RESULTS: At the genomic level, three independent methods confirmed the overall genetic correlation between SCZ and IBD, including CD and UC. Local genetic correlations were also observed across multiple chromosomal regions. At the single-nucleotide polymorphism (SNP) level, we performed a conjFDR analysis, which indicated a genetic overlap between the two traits. By integrating conjFDR analysis with MTAG, we successfully identified several shared genetic loci, including SLC39A8, BACH2, ZNF365, NOD2, PLCL1, and KIF21B. CONCLUSION: The present study provides a novel perspective on the correlation between SCZ and IBD, potentially advancing the understanding of the genetic architecture and mechanisms of co-morbidities in both diseases.
IL17RA genetic variants are associated with susceptibility and severity of psoriasis.
de Alcantara CC, Vissoci Reiche EM, Moreira CR … +4 more , Luz TF, Mário Martin LM, Batisti Lozovoy MA, Colado Simão AN
Hum Immunol · 2025 Jul · PMID 40347901 · Publisher ↗
BACKGROUND: Genetic variants that can play an important role in psoriasis (PsO) ethiology and pathophysiology. OBJECTIVE: To evaluate the association between the IL17RA genetic variants with the susceptibility and severi...
BACKGROUND: Genetic variants that can play an important role in psoriasis (PsO) ethiology and pathophysiology. OBJECTIVE: To evaluate the association between the IL17RA genetic variants with the susceptibility and severity of PsO. METHODS: This study included 154 patients with PsO and 154 healthy controls. The severity of PsO was determined using Psoriatic Activity and Severity Index (PASI). The IL17RA single nucleotide variants T > C rs2241043, A > G rs2241049, and G > A rs6518661 were genotyped. RESULTS: The IL17RA A > G (rs2241049) GG genotype was associated with protection against PsO [odds ratio (OR): 0.391, 95 % confidence interval (CI):0.199-0.768, p = 0.006)] while the IL17RA T > C (rs2241043) CC genotype and the IL17RA G > A (rs6518661) AA genotype were associated with the PsO severity (OR = 0.30, 95 % CI 0.10-0.093, p = 0.020 and OR = 0.22, 95 % CI 0.05-0.99, p = 0.020, respectively). CONCLUSION: The results demonstrated that the IL17RA A > G (rs2241049) GG genotype may be a protective factor against the development of PsO and the CC genotype of the IL17RA T > C (rs2241043) and the AA genotype of the IL17RA G > A (rs6518661) variants were associated with protection against the severity of PsO. Considering that these variants are located in intronic regions of the IL17RA, other genetic and epigenetic mechanisms involved in these associations should be investigated.
Preventing hyperacute rejection in a deceased donor kidney transplant recipient.
Zhang Q, Elsheikh NE, Hickey MJ … +13 more , Butler C, Sosa R, Choi SM, Timofeeva O, Huang Y, Shaikh S, Gandhi M, Chen LX, Perez R, Goussous N, Alexopoulos S, Sageshima J, Reed EF
Hum Immunol · 2025 Jul · PMID 40334348 · Publisher ↗
A 36-year-old, highly sensitized (cPRA 99.99 %) male listed for his third kidney transplant for more than 12 years received a deceased donor offer. The virtual crossmatch (VXM) indicated that the patient had two weak don...
A 36-year-old, highly sensitized (cPRA 99.99 %) male listed for his third kidney transplant for more than 12 years received a deceased donor offer. The virtual crossmatch (VXM) indicated that the patient had two weak donor-specific antibodies (DSA) to DR10 and DP17 against potential Donor 1, which would correlate with a negative T/B physical crossmatch (PXM). However, the PXM results were unexpectedly positive over 300 median channel shifts (MCS). Investigation into the discrepancy ruled out new sensitization and prozone effect. Repeated PXM showed results consistent with the initial findings and ruled out a sample swap of the donor cells or patient serum.Conditions such as auto-immune diseases and HIV, which could cause false positive PXM were also ruled out. Coincidentally, the patient received a second deceased donor offer (Donor 2) with identical HLA typing to Donor 1 from the same Organ Procurement Organization (OPO) on the same day. Further investigation of the ethnicity of the two donors revealed that Donor 1 was of African American (AFA) origin, and Donor 2 was Caucasian (CAU). Based on HLA disequilibrium, it is highly impossible that the two donors would share the same HLA typing, as A30-B42-DR18-DQ4 is the most common haplotype in AFA, and nearly absent in CAU populations. Repeating HLA typing of Donor 1 showed discrepant results from the initial HLA typing provided by the OPO. The updated VXM with the correct typing for Donor 1 revealed strong DSA to A1, A33, Cw8, DQ7, and DQA1*05, which corresponded with the PXM result.
Profiling the genetic diversity of the HLA system in Mexico using 9-locus allele and haplotype frequencies from donors in the NMDP Mexico donor center.
Madbouly A, Bashyal P, Banos A … +7 more , Ramirez J, Whitaker C, Fernandez-Vina M, Springer B, Ybarra Y, Maiers M, Bolon YT
Hum Immunol · 2025 Jul · PMID 40334347 · Publisher ↗
Profiling the HLA diversity at the population level benefits multiple clinical and anthropological applications, such as tracing population migration, identifying genetic relationships between different groups, quantifyi...
Profiling the HLA diversity at the population level benefits multiple clinical and anthropological applications, such as tracing population migration, identifying genetic relationships between different groups, quantifying the added diversity in a global donor pool and matching for solid organ and stem cell transplantation. We calculated nine-locus HLA-A ∼ C ∼ B ∼ DRB1 ∼ DRB3/4/5 ∼ DQA1 ∼ DQB1 ∼ DPA1 ∼ DPB1 allele and haplotype frequencies in about 170,000 volunteer donor genotypes from the NMDP Mexico (NMDP MX, previously Be The Match Mexico) donor center. These donors are predominantly of Mexican ancestry recruited from multiple regions in Mexico. The goal of the study was to describe the HLA genetic profiles of the Mexican population and investigate the contribution of these donors' HLA in serving Mexican, US and international patients in need of hematopoietic cell transplants. Additionally, we estimated that almost all Mexican patients will have an available 5 of 8 or better matched donor in the NMDP MX donor center with matches also available for some of the Latino patients in the U.S. We demonstrate that Mexican populations clustered genetically and shared multiple frequent alleles and haplotypes with populations from the US Mexican or Chicano, US South/Central American Hispanic, and some Latino populations. Operationally, 78 % of NMDP Mexico donors contributed genotypes that were observed a total of three times or less on the registry, increasing the diversity of the overall NMDP registry. More than 300 donor collections were facilitated through the NMDP MX donor center serving mostly Hispanic/Latino patients in the US and abroad. This study highlights the importance of adding the NMDP MX donors to the worldwide donor pool and paves the way for a data-driven strategy for future planning and donor recruitment.
Risk of acute graft-versus-host disease in recipients with IL-10 promoter polymorphism rs1800872, but not IL-10 receptor β polymorphism rs2834167, after single-unit cord blood transplantation.
Konuma T, Hamatani-Asakura M, Monna-Oiwa M … +6 more , Kato S, Andoh S, Oda Y, Yokoyama K, Nannya Y, Takahashi S
Hum Immunol · 2025 Jul · PMID 40300933 · Publisher ↗
The function of Interleukin-10 (IL-10) is affected by polymorphisms in the promoter region of the IL-10 gene and IL-10 receptor β (IL-10Rβ), which are associated with acute and chronic graft-versus-host disease (GVHD) in...
The function of Interleukin-10 (IL-10) is affected by polymorphisms in the promoter region of the IL-10 gene and IL-10 receptor β (IL-10Rβ), which are associated with acute and chronic graft-versus-host disease (GVHD) in allogeneic hematopoietic cell transplantation from adult donors. We investigated the effect of recipient and donor IL-10 (rs1800872) and IL-10Rβ (rs2834167) polymorphisms on outcomes in adults who underwent cord blood transplantation (CBT) at our institution. A total of 158 recipients and 136 donors were included in this study. In the multivariate analysis, an rs1800872 GT or TT recipient had a significantly lower risk of grades II to IV acute GVHD compared to a GG recipient (hazard ratio, 0.60; 95 % confidence interval, 0.37-0.96; P = 0.036). Our data showed that the IL-10 rs1800872 polymorphism in recipients may serve as a predictor of grade II to IV acute GVHD risk following single-unit CBT.
Practical guide to personnel competency assessment in clinical histocompatibility laboratories.
Ho S, Hod-Dvorai R, Bravo-Egana V … +9 more , Kheradmand T, Bishop C, Brown NK, Eilrich H, O'Shields EF, Houp JA, Sanfilippo AM, Timofeeva O, American Society for Histocompatibility and Immunogenetics (ASHI) Professional Standards Division
Hum Immunol · 2025 Jul · PMID 40288922 · Publisher ↗
Deficiencies in personnel competency assessment are among the most frequent citations of the Clinical Laboratory Improvement Amendments (CLIA) and Accreditation Organizations with deeming authority, such as the American...
Deficiencies in personnel competency assessment are among the most frequent citations of the Clinical Laboratory Improvement Amendments (CLIA) and Accreditation Organizations with deeming authority, such as the American Society for Histocompatibility and Immunogenetics (ASHI). Despite having been introduced decades ago in the CLIA regulations of 1988, potential confusion and misinterpretation on who, what, when, and how to assess competency remain. Herein, the ASHI Professional Standards Division taskforce, consisting of leadership from the Accreditation Review Board, the American College of Histocompatibility and Immunogenetics, the Proficiency Testing Committee, and the Quality Assurance and Standards Committee, sought to provide clarifications, guidelines, recommendations, and best practice suggestions on how personnel competency should be assessed in clinical histocompatibility laboratories to achieve regulatory compliance.
A glance at the geographical distribution of histocompatibility laboratories.
Bravo-Egana V, Abraha J, Huang Y … +2 more , Kheradmand T, Ho S
Hum Immunol · 2025 Sep · PMID 40280810 · Publisher ↗
Histocompatibility laboratories (HLs) provide essential histocompatibility and immunogenetics (H&I) testing in support of organ and stem cell transplantation, diagnosis of diseases and risk assessment of drug-induced adv...
Histocompatibility laboratories (HLs) provide essential histocompatibility and immunogenetics (H&I) testing in support of organ and stem cell transplantation, diagnosis of diseases and risk assessment of drug-induced adverse reactions associated with HLA variants, and beyond. Their geographical distribution and the accreditation organizations that provide regulatory oversight have never been profiled. To understand the characteristics of HLs and their global distribution, a taskforce was established by the American Society for Histocompatibility and Immunogenetics (ASHI) Accreditation Review Board (ARB) to gather this data. Our study indicates there are at least 593 HLs routinely providing testing services across 58 countries and 6 continents, with two major organizations, ASHI and EFI, providing accreditation. The data presented here indicates that the distribution of HLs highly depends on the size and economic development of the countries and geographical areas where they are located. This report highlights the benefits of standardization and potential for cooperation among HLs and professional histocompatibility and immunogenetics societies and organizations worldwide.
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