Human Immunology[JOURNAL]
Sun
200 papers
Prevalence and Dynamics of HLA donor-specific antibodies in simultaneous liver-kidney transplantation.
Zhang Q, Pulido MA, Soltero S … +14 more , Butler C, Lum E, Abdalla B, Kendrick E, Yabu JM, Pham PT, Bunnapradist S, Veale J, Gritsch AH, Danovitch GM, Venick RS, Pickering H, Farmer DG, Reed EF
Hum Immunol · 2026 Apr · PMID 41687354 · Publisher ↗
AIMS: Donor-specific antibodies (DSAs) negatively affect outcomes in solid organ transplantation outcomes, but their significance in simultaneous liver-kidney (SLK) transplant recipients remains incompletely understood....
AIMS: Donor-specific antibodies (DSAs) negatively affect outcomes in solid organ transplantation outcomes, but their significance in simultaneous liver-kidney (SLK) transplant recipients remains incompletely understood. This study investigates the prevalence, dynamics, and clinical impact of both preformed and posttransplant DSAs in patients undergoing SLK transplantation. METHODS: A retrospective cohort of 151 SLK recipients transplanted at UCLA from 2014 to 2024 was analyzed. Assessment of DSA status, DSA strength (mean fluorescence intensity (MFI), and clinical outcomes including rejection and patient survival were performed. Patient survival was analyzed using Kaplan-Meier survival curves. RESULTS: Of the 151 patients, 35 (23.2 %) were transplanted with preformed DSAs. Among 110 patients with posttransplant DSA testing, 25 (22.7 %) developed new DSAs, with a significantly higher incidence in females (37.8 % vs. 15.1 %, p = 0.014). Preformed DSAs were not significantly associated with rejection in kidney, liver, or combined allografts. However, posttransplant DSAs correlated with increased rejection risk: 3/25 (12 %) vs. 1/85 (1.2 %) in kidney (p < 0.05) alone and 12 % vs. 8.2 % in liver (p < 0.05) alone. Four patients experienced antibody-mediated rejection, and all four patients had either preformed or posttransplant de novo DSA. Preformed Class II DSAs were more persistent posttransplant and were more frequently associated with rejection (p < 0.05). Both preformed and posttransplant DSAs significantly declined over time posttransplant, although class II DSAs exhibited more resistance to clearance compared to class I DSA. Survival analysis revealed no statistically significant differences among patients without DSA, preformed DSA and posttransplant DSA groups; however, patients without DSAs had the highest 5-year survival (74.3 %), while those developing de novo DSAs beyond 3 months had the lowest (48.4 %). CONCLUSIONS: In SLK recipients, posttransplant DSAs, especially class II, are significantly associated with increased rejection risk and may contribute to reduced long-term survival. Although preformed DSAs showed less clinical impact, persistent class II DSAs warrant closer monitoring. Larger studies are needed to validate these findings and guide individualized immunological risk assessment.
The role of complement protein and complement regulatory protein in diabetic nephropathy.
Jiang X, Sun Z
Hum Immunol · 2026 Apr · PMID 41687353 · Publisher ↗
BACKGROUND: Diabetic nephropathy is one of the main causes of end-stage renal disease, with dysregulation of the complement system playing a critical role in its pathogenesis. However, the specific mechanisms, key effect...
BACKGROUND: Diabetic nephropathy is one of the main causes of end-stage renal disease, with dysregulation of the complement system playing a critical role in its pathogenesis. However, the specific mechanisms, key effector molecules, and relevant therapeutic targets still require further investigation. METHODS: This review involves searching databases such as PubMed and Web of Science to identify and integrate key studies on the role of complement proteins and regulatory proteins in diabetic nephropathy. This is a narrative review integrating experimental and clinical studies, rather than a formal systematic review. The analysis systematically examines the mechanisms of the complement system in disease progression and its potential as a therapeutic target. RESULTS: This review collectively suggests that the hyperglycemic environment characteristic of diabetic nephropathy activates both the complement alternative and lectin pathways, continuously driving the complement cascade and generating key effector molecules (such as C5a and the membrane attack complex). These molecules directly lead to podocyte injury, glomerular inflammation, and fibrosis. Concurrently, dysfunction of complement regulatory proteins (such as CD59 and CD55) results in excessive activation of complement proteins, collectively accelerating the progression of diabetic nephropathy to end-stage renal disease. In terms of intervention strategies, inhibitors targeting specific complement components (such as C3 and C5) have shown protective effects in preclinical models. CONCLUSION: Dysregulation of the complement system is an important pathogenic mechanism in diabetic nephropathy. A deeper understanding of this regulatory network provides a solid theoretical foundation for developing targeted and precise therapeutic strategies aimed at the complement system.
A wide proteome analysis to engineer an efficient epitope based vaccine against Salmonella typhi: An immunoinformatic study.
Beiranvand M, Shams N, Jaydari A … +2 more , Nazifi N, Khademi P
Hum Immunol · 2026 Apr · PMID 41679099 · Publisher ↗
BACKGROUND: Typhoid fever, a potentially fatal disease caused by Salmonella enterica serovar Typhi, requires effective vaccines. This study aimed to design a recombinant subunit vaccine using the most immunogenic protein...
BACKGROUND: Typhoid fever, a potentially fatal disease caused by Salmonella enterica serovar Typhi, requires effective vaccines. This study aimed to design a recombinant subunit vaccine using the most immunogenic proteins from the Salmonella Typhi proteome. METHODS: Initially, the most antigenic proteins were selected to predict linear T-cell, B-cell, and IFN-γ epitopes. A recombinant construct incorporating these epitopes, peptide linkers, and a molecular adjuvant was designed. Comprehensive evaluation assessed physicochemical properties, solubility, secondary/tertiary structure, antigenicity, and immune stimulation potential. Molecular docking and dynamics simulations investigated binding to the TLR4/MD2 receptor complex. RESULTS: Seven proteins from 4322 were chosen for epitope prediction, yielding a 655-amino acid construct. Physicochemical analysis showed 40.31 % hydrophobic amino acids, an aliphatic index of 53.66, GRAVY index of -0.712, and instability index of 22.34. Structural composition was 53.53 % alpha-helix, 8.85 % extended strand, and 40.61 % random coil. Immune simulations demonstrated significant enhancement of primary/secondary humoral and cellular immune responses. The vaccine construct effectively bound the TLR4/MD2 receptor via significant hydrogen bonding (affinity: -1019.1 kcal/mol). Molecular dynamics simulations confirmed the stability of this interaction over 200 ns, demonstrating that both the vaccine candidate and receptor remained structurally stable throughout the simulation period. CONCLUSION: Typhoid vaccine candidate shows immunogenic properties, robust immune responses and stable TLR4/MD2 receptor binding.
Preclinical and clinical developments in Treg therapy for heart transplantation: Critical assessment and translational challenges.
Mengrelis K, Wolner L, Lakatos RL … +2 more , Zuckermann A, Pilat N
Hum Immunol · 2026 Apr · PMID 41671722 · Publisher ↗
Regulatory T cells (Tregs) represent a promising approach to induce donor-specific tolerance in cardiac transplantation, potentially reducing reliance on chronic immunosuppression. This review critically evaluates precli...
Regulatory T cells (Tregs) represent a promising approach to induce donor-specific tolerance in cardiac transplantation, potentially reducing reliance on chronic immunosuppression. This review critically evaluates preclinical and clinical evidence. Preclinical studies demonstrate that adoptively transferred Tregs prolong cardiac allograft survival and prevent chronic allograft vasculopathy (CAV) in murine models through multiple suppressive mechanisms. Phase I/II trials in kidney and liver transplantation have already confirmed safety and feasibility of polyclonal Treg cell therapy, with evidence of immunosuppression reduction in selected patients. However, no cardiac-specific trials have been completed in adults, and critical translational barriers persist including limited in vivo persistence, phenotypic instability under inflammatory conditions, manufacturing complexity and incompatibility with deceased donor timelines. Emerging approaches show promise: CAR-engineered Tregs targeting HLA-A2 demonstrate enhanced specificity and establish infectious tolerance in preclinical cardiac transplant models, with preliminary data from the first-in-human kidney transplant data suggesting safety and efficacy. Thymus-derived Tregs offer advantages for pediatric recipients, with the first treated cardiac transplant patient showing preserved Treg homeostasis. This review identifies key research priorities necessary to translate Treg therapy into clinical cardiac transplantation practice.
Unique case of false-positive pan-HLA-A antibody detection in LABScreen single antigen bead assay.
Jarret M, Rachel B, Lydia B … +5 more , Justin K, Robyn P, Nathan T, Laurie W, Gandhi MJ
Hum Immunol · 2026 Apr · PMID 41671721 · Publisher ↗
Accurate detection of HLA antibodies is essential for assessing immunologic risk in transplantation. Solid-phase antibody assays (SPA), particularly Luminex-based single-antigen bead (SAB) assay offer high sensitivity, b...
Accurate detection of HLA antibodies is essential for assessing immunologic risk in transplantation. Solid-phase antibody assays (SPA), particularly Luminex-based single-antigen bead (SAB) assay offer high sensitivity, but are prone to false reactions that may lead to clinical misinterpretation. While false-positive pan-locus patterns have been described for HLA-C/DR, pan-HLA-A reactivity has not been previously reported. We present a patient who developed pan-HLA-A reactivity detected by LABScreen™ SAB one year after combined liver-kidney transplantation. Repeat testing and Presorb™ treatment yielded identical results. To investigate causes, testing with acid-treated beads ruled out antibodies to denatured HLA. An alternative SAB platform (LIFECODES® LSA™) and LABScreen™ Mixed beads were negative. Surrogate flow crossmatches with two unrelated donors were negative, confirming absence of cell-reactive antibodies. This represents the first documented case of false-positive pan-HLA-A reactivity confined to a single commercial SAB product. Recognition of such artifacts is essential to prevent misclassification of antibody specificity.
HLA-G alleles in Italian patients with locally advanced rectal cancer (LARC).
Scarabel L, Castelli EC, Zorzi M … +13 more , De Mattia E, Milan N, Giacomin A, Innocente R, Navarria F, Gigante M, Mascarin M, Canzonieri V, Ongaro E, Cannizzaro R, Belluco C, Toffoli G, Cecchin E
Hum Immunol · 2026 Mar · PMID 41655323 · Publisher ↗
AIM: High-resolution HLA-G typing in selected patients with locally advanced rectal cancer (LARC) enrolled at the National Cancer Institute "Centro di Riferimento Oncologico di Aviano (CRO) IRCCS" (Italy) (CRO-2023-77)....
AIM: High-resolution HLA-G typing in selected patients with locally advanced rectal cancer (LARC) enrolled at the National Cancer Institute "Centro di Riferimento Oncologico di Aviano (CRO) IRCCS" (Italy) (CRO-2023-77). METHODS: HLA-G genotyping was conducted in 405 LARC patients with allele identification at the genomic (4-field), exonic (3-field), and protein (2-field) levels. Genomic DNA was extracted from buffy coat samples, and full-length HLA-G amplicons were obtained by long-range PCR. DNA libraries were prepared with the QIAseq FX DNA Library kit (Qiagen) and sequenced on the Illumina MiSeq platform (2x250bp). High-coverage sequencing data (>50x) were analyzed using an updated version (v5) of the hla-mapper workflow. RESULTS: This LARC cohort predominantly included patients from the North-East regions of Italy. Variants in the HLA-G gene were mostly located in intronic (50, 41.0%) and regulatory regions, including promoter, 5'UTR, and 3'UTR (50, 41%), compared to exonic regions (22, 18.0%). Most variants were bi-allelic single nucleotide variants, although insertions/deletions were also detected. Almost half of patients (186, 45.9%) showed at least one missense (rs41551813, rs770412396, rs12722477, or rs12722482), start-lost (rs143732275), or frameshift (rs41557518) variants. Moreover, in 60 (14.8%) patients, 39 different rare or putative novel variants were found, all in heterozygosity. One patient carried the G*01:01:11 rare allele, previously reported only in two Brazilian relatives of Italian ancestry. The most prevalent allotypes were HLA-G*01:01, HLA-G*01:04, HLA-G*01:06, HLA-G*01:03, and the HLA-G*01:05N null allele, consistent with European reference data. Our LARC cohort shows frequencies similar to those reported for the Italian population. The differences observed comparing HLA-G 4-field allele frequencies between this LARC cohort and the European population for G*01:01:01:01 (p = 0.0004, q = 0.0048), G*01:01:02:01 (p = 0.0033, q = 0.0132), G*01:01:01:05 (p = 0.0012, q = 0.0072), G*01:01:01:04 (p = 0.0093, q = 0.0279), G*01:03:01:02 (p = 0.0354, q = 0.0708), and rare 4-field alleles (p = 0.0117, q = 0.0281) reflected the known allele differences across European countries. CONCLUSIONS: This study represents the largest Italian cohort to date with comprehensive high-resolution HLA-G genotyping in LARC patients. Ongoing analyses aim to correlate these genetic findings with clinical parameters and HLA-G expression levels in liquid biopsies. This integrative approach may identify HLA-G-related genetic factors influencing prognosis, therapeutic response, and treatment-related adverse events in patients with LARC.
The limited clinical utility of neutrophil-to-lymphocyte ratio in systemic lupus erythematosus: A meta-analysis with external validation.
Du J, Tu X, He M … +4 more , Zuo Y, Chen L, Li M, Tang W
Hum Immunol · 2026 Apr · PMID 41650750 · Publisher ↗
OBJECTIVE: To evaluate the diagnostic and discriminative value of the neutrophil-to-lymphocyte ratio (NLR) in systemic lupus erythematosus (SLE). METHODS: A meta-analysis was conducted using literature from inception to...
OBJECTIVE: To evaluate the diagnostic and discriminative value of the neutrophil-to-lymphocyte ratio (NLR) in systemic lupus erythematosus (SLE). METHODS: A meta-analysis was conducted using literature from inception to January 2026. Pooled estimates were calculated, and external validation was provided by a single-center study (n = 290). RESULTS: Forty studies were included. NLR was significantly higher in SLE patients than healthy controls (SMD = 0.850). Patients with lupus nephritis (LN) and active disease also exhibited elevated NLR. A positive correlation was found between NLR and SLEDAI scores (pooled r = 0.330); however, this decreased to 0.200 after trim-and-fill adjustment for publication bias, a finding consistent with external validation (r = 0.210). Its discriminatory accuracy was generally limited (AUC 0.668-0.757), with ethnicity and treatments being major sources of heterogeneity. CONCLUSION: NLR is elevated in SLE, LN, and active disease, showing a weak positive correlation with disease activity. However, its clinical utility is influenced by ethnicity and treatment, indicating that it should not be used as an independent biomarker but may have a role as part of a combined assessment.
Novel association of HLA-DQA1 and HLA-DPB1 alleles with acute myeloid leukemia susceptibility in (Central Asian) Kazakhstani population: A case-control study.
Turganbekova A, Burkitbayev Z, Zhanzakova Z … +6 more , Baimukasheva D, Saduakas Z, Khamitova D, Abdrakhmanova S, Masalimov Z, Almawi WY
Hum Immunol · 2026 Mar · PMID 41633310 · Publisher ↗
BACKGROUND: Acute myeloid leukemia (AML) is a diverse hematological cancer characterized by clonal growth of myeloid precursors in the bone marrow. Although the core genetic pathways involved in AML development are not c...
BACKGROUND: Acute myeloid leukemia (AML) is a diverse hematological cancer characterized by clonal growth of myeloid precursors in the bone marrow. Although the core genetic pathways involved in AML development are not completely understood, a connection between specific HLA variants and a predisposition to AML, as well as graft-versus-leukemia effects in transplantation, has been observed across various ethnic groups. OBJECTIVE: Using high-resolution genotyping, this study investigates the relationship between HLA Class I and Class II alleles and the risk of developing AML in the Kazakhstani population. METHODS: The study included 123 patients diagnosed with AML and 350 unrelated healthy controls selected from the national registry of hematopoietic stem cell donors. HLA Class I (HLA-A, -C, -B) and Class II (HLA-DRB1, -DQA1, -DQB1, -DPB1) high-resolution genotyping was conducted using next-generation sequencing. Statistical significance was assessed with chi-square tests (and Fisher's exact tests where suitable). RESULTS: Class II alleles showed stronger associations with AML than Class I alleles. At the DQA1 locus, DQA1*05:01:01, DQA1*03:01:01, DQA1*01:01:01, and DQA1*01:02:01 were significantly protective (p < 0.001), while DQA1*04:01:01 was strongly linked to risk (p < 0.001). Protective DPB1 alleles included DPB1*04:01:01 and DPB1*02:01:01, whereas DPB1*01:01:01 increased susceptibility. Among Class I alleles, only HLA-C*02:02:01 was protective, while HLA-B*57:01:01 was associated with a higher AML risk. CONCLUSIONS: Class II alleles, especially those within DQA1 and DPB1, are important genetic factors influencing AML susceptibility in the Kazakhstani population.
HLA typing of HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1 loci of 226 individuals from three metropolitan areas in South Africa.
Suzuki A, Baguma R, Sawry S … +11 more , Gill K, Roux JL, Nana A, Patel F, Garrett N, Sigal A, Moore PL, Fairlie L, Riou C, Burgers WA, Valley-Omar Z
Hum Immunol · 2026 Mar · PMID 41633309 · Publisher ↗
The aim of this study was to characterize HLA diversity in individuals from clinical research sites in order to better understand T cell responses to COVID-19 vaccines in relation to their HLA profiles. Next-generation s...
The aim of this study was to characterize HLA diversity in individuals from clinical research sites in order to better understand T cell responses to COVID-19 vaccines in relation to their HLA profiles. Next-generation sequence-based typing of the HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1 loci is reported for 226 individuals from three metropolitan areas in South Africa. Overall, the frequencies of both class I and class II HLA alleles in this study were comparable to those identified in other South African studies. While a more uniform allele frequency prevalence was noted for HLA class I and HLA-DRB1 genes, an allele bias was noted within our population for HLA-DPB1 and -DQB1 alleles, where three most prevalent alleles accounted for allele frequencies of between 12.3 and 29.8%. Our HLA genotyping data will contribute to an expanding catalogue of HLA data from Africa, which are available in the Allele Frequencies Net Database under identifiers 3826, 3827 and 3828.
Cytotoxic and immunomodulatory activity of CD151-LEL-based peptides in breast cancer and THP-1 cells.
Vempati RK, Malla R
Hum Immunol · 2026 Mar · PMID 41628581 · Publisher ↗
CD151, a cell surface oncoprotein belongs to the tetraspanin family, drives metastasis, drug resistance, and immune escape, and is recognized as a tumor-associated antigen (TAA). In the screening phase, a positive correl...
CD151, a cell surface oncoprotein belongs to the tetraspanin family, drives metastasis, drug resistance, and immune escape, and is recognized as a tumor-associated antigen (TAA). In the screening phase, a positive correlation between CD151 expression and amplification of CCND1, ERBB2, and MYC genes as well with breast cancer (BC) metastasis was observed using data from different GEO datasets. This study identified three immunogenic peptides within the large extracellular loop (LEL) of CD151 using in silico approaches: one each of CTL and HTL epitope, which bind strongly to class I and II MHC molecules, and one B-cell epitope, eliciting a robust IgG immune response. In the validation phase, a multiepitope was constructed by incorporating high immunogenic peptides and adjuvants, which showed significant antigenicity and broader population coverage. The results also showed a hierarchy in the binding of multiepitope with key immune receptor molecules, highlighting their potential in activating the innate and adaptive immune responses. Furthermore, molecular dynamic simulation and normal mode analysis studies uncovered a strong interaction between the multiepitope construct and TLR2. The simulation of immune system activation by the multiepitope construct using the C-ImmSim web server showed a strong B- and T-cell response with potential activation of natural killer and dendritic cells. The results also showed active antigen internalization by macrophages, their presentation to other immune cells, and IL-2 and IFN-γ secretion. In addition, AntiCP web server predicted both CTL and HTL epitopes as anticancer peptides. The in vitro study validated that synthetic peptides corresponding to CD151-LEL-based CTL and HTL peptides induced cytotoxicity in BC cell lines MDA-MB 231 and MCF-7. They reduced the CCND1mRNA levels in MDA-MB-231 and MCF-7 cells, while MYC mRNA levels in MCF-7 cells. Also, they significantly induced the secretion of IFN-γ and IL-2 while reducing the secretion of IL-10. Furthermore, conditioned media from the treated BC cells induced the proliferation of PMA treated monocyte like THP-1 cells and provoked the secretion of IL-6, while reducing IL-10. These findings suggest that the CD151-LEL-based peptides and their engineered multiepitope construct represent a prospective vaccine candidate for in vivo experimental validation, which can be used as a therapeutic vaccine for breast cancer.
A multipronged Tα1 reset of CD8 T cell cytotoxicity against breast cancer.
Mishra S, Telang G, Sureshbabu A … +4 more , Kulkarni S, Thayagrajan S, Kumar AWS, Singh R
Hum Immunol · 2026 Mar · PMID 41619634 · Publisher ↗
Thymosin α1 (Tα1) is an endogenous thymic peptide that enhances immune competence through activation of T cells, dendritic cells, and innate immune pathways. However, its direct impact on CD8 T cell-mediated antitumor im...
Thymosin α1 (Tα1) is an endogenous thymic peptide that enhances immune competence through activation of T cells, dendritic cells, and innate immune pathways. However, its direct impact on CD8 T cell-mediated antitumor immunity in breast cancer remains unclear. In this study, CD8 T cells isolated from peripheral blood of ten healthy donors were cultured under unstimulated, CD3/CD28-stimulated, Tα1-treated, or exhaustion-rescue conditions to evaluate cytotoxic activity against MDA-MB-231 breast cancer cells and CD44 cancer stem-like cells (CD44 CSC-like cells). Tα1 significantly enhanced CD8 T cell-mediated apoptosis, suppressed tumor cell proliferation, and increased granzyme B secretion beyond CD3/CD28 stimulation alone. In exhausted T cells, Tα1 partially restored effector function and reduced PD-1, TIM-3, and LAG-3 expression. Complementary transcriptomic analysis using a compact four-gene Tα1 Response Index (Tα1-RI: TLR9, TLR2, IRF1, NLRC5) in TCGA-BRCA (n = 1,112) confirmed positive correlations with antigen presentation and cytotoxic programs and enrichment in CD8-like T cells in single-cell datasets. Collectively, these findings demonstrate that Tα1 enhances CD8 T cell cytotoxicity while alleviating exhaustion, supporting its potential as an adjunct immunomodulator for improving immune surveillance in breast cancer.
Gene alterations in inborn errors of immunity and their presence in cancers: Implications for oncogenesis, progression, and outcomes.
Lokanc S, Sipila P, Cuvelier GDE … +5 more , Murguía-Favela L, Wright NA, Grunebaum E, Bose P, Narendran A
Hum Immunol · 2026 Mar · PMID 41616493 · Publisher ↗
Inborn Errors of Immunity (IEI) are genetic disorders impairing the immune system, increasing susceptibility to infections, autoimmunity, inflammation, and malignancies. Mutations in over 500 genes have been shown to cau...
Inborn Errors of Immunity (IEI) are genetic disorders impairing the immune system, increasing susceptibility to infections, autoimmunity, inflammation, and malignancies. Mutations in over 500 genes have been shown to cause IEI. This study investigated IEI-related differential gene expression by examining the somatic transcriptomes of cancers. RNA-sequencing data from cancers were obtained from TCGA and TARGET databases, alongside healthy tissue data from GTEx, and the differentially expressed gene set was filtered for 592 IEI-related genes. To examine the differential expression of genes across cancers, odds ratios were computed for enrichment of IEI-related genes. Pathway analysis on the differentially expressed IEI-related genes identified immune pathways that are significantly represented. IEI-genes that were significantly dysregulated include TMPRSS15, SEMA3E, ANGPT1, CFH, F5, CFB, CFD, CFH, and CR2. Interestingly, complement-related pathways were the most altered in our analysis. Furthermore, IEI-related genes are more likely to be differentially expressed compared to non-IEI genes in certain cancers. This study presents bioinformatic analyses of pan-cancer genomic datasets, identifying distinct IEI-associated gene expression changes. The findings provide insights into the role of immunological pathways, specifically the complement system, in cancer. Further investigation into the identified gene alterations could advance the care of a vulnerable group of cancer patients.
Meta-analysis of the association between HLA-G 14-bp insertion/deletion polymorphism and susceptibility to viral infections and cancer risk.
Bourogâa H, Dhouioui S, Zaibi H … +5 more , Mokrani A, Boujelbene N, Rahman MA, Harrath AH, Zidi I
Hum Immunol · 2026 Mar · PMID 41592445 · Publisher ↗
BACKGROUND/OBJECTIVE: HLA-G 14-bp insertion/deletion (I/D) polymorphism has been linked to both cancer susceptibility and various viral infections. This meta-analysis examined the relationship between HLA-G 14-bp I/D pol...
BACKGROUND/OBJECTIVE: HLA-G 14-bp insertion/deletion (I/D) polymorphism has been linked to both cancer susceptibility and various viral infections. This meta-analysis examined the relationship between HLA-G 14-bp I/D polymorphism with different viral infections on patients with or without complications of cancer. METHODS: We carried out a meta-analysis according to PRISMA guidelines, pooling data from 26 case-control studies on HLA-G 14-bp I/D polymorphism including association with viral diseases and cancer cases. 5906 cases and 6963 healthy controls were included in the meta-analysis. RESULTS: Analysis under the random model showed lack of association between HLA-G 14-bp I/D polymorphism and viral infection either in the presence or absence of cancer in the overall population. Interestingly, subgroup analysis revealed variable outcomes across the subgroups analysed. Heterogeneous results depended mainly on virus characteristics (type, genome and family) and ethnicity. The HLA-G 14-bp I/D polymorphism was associated with Hepadnaviridae (DNA genome) infection in patients without cancer under the allelic model (D vs. I: OR = 0.801, 95% CI = 0.714-0.898, p < 0.001). Conversely, it was associated with Flaviviridae (RNA genome) infection in the presence of cancer under the same model (D vs. I: OR = 1.972, 95% CI = 1.022-3.806, p = 0.043). Whereas the HLA-G 14-bp I/D polymorphism was not associated with Coronaviridae infection or Retroviridae infection in patients without cancer. The results of analysed subgroups influenced by ethnicity indicated that HLA-G 14-bp I/D polymorphism was associated with viral infection under the allelic model for mixed populations and under the allelic model and the genotypic models for Caucasians. In complicated infections with the presence of cancer, the HLA-G 14-bp I/D polymorphism is associated with viral infection under the allelic model (D vs. I: OR = 1.855, 95% CI = 1.459-2.358, p < 0.001) and genotypic models (DD + DI vs II: OR = 4.410, 95% CI = 2.754-7.064, p < 0.001; and DD vs DI + II : OR = 1.434, 95% CI = 0.984-2.088, p = 0.061) in Caucasians. Particularly, it gives protection against hepadnavirus infection in patients without cancer for Caucasians under the allelic model (D vs. I: OR = 0.752, 95% CI = 0.640-0.883, p = 0.001) and genotypic (DD + DI vs. II: OR = 0.534, 95% CI = 0.422-0.677, p < 0.001 ; DD + II vs. DI: OR = 1.819, 95% CI = 1.449-2.284, p < 0.001; and DI vs. II: OR = 0.509, 95% CI = 0.399-0.650, p < 0.001) models. But it seems to offer a protection against flavivirus infection in Caucasians when expressing cancer under the allelic (D vs. I) and genotypic (DD vs. DI + II; DD + DI vs. II; DD + II vs. DI; DI vs. II; and DD vs. II) models. CONCLUSION: This meta-analysis highlights the potential implication of virus structure, patient history, and ethnicity in HLA-G 14-bp I/D polymorphism regulation. This polymorphism appears to be associated withcancer susceptibility and immune protection during viral infection. It is hoped that further research will give more clinical utility of HLA-G polymorphism as a valuable molecular tool for prognostic assessment and therapy planning.
Modulatory effect of magnesium sulfate on NLRP3 inflammasome expression by human monocytes stimulated in vitro with monosodium urate.
Franco GO, Romao-Veiga M, Ribeiro-Vasques VR … +4 more , Braga da Silva P, de Oliveira LRC, Peracoli MTS, Peracoli JC
Hum Immunol · 2026 Mar · PMID 41570703 · Publisher ↗
The NLRP3 inflammasome contributes to inflammation in preeclampsia (PE), a hypertensive pregnancy disorder associated with immune imbalance. Magnesium sulfate (MgSO), the standard therapy for eclampsia, also exhibits ant...
The NLRP3 inflammasome contributes to inflammation in preeclampsia (PE), a hypertensive pregnancy disorder associated with immune imbalance. Magnesium sulfate (MgSO), the standard therapy for eclampsia, also exhibits anti-inflammatory properties linked to intracellular calcium regulation. This study investigated the modulatory effect of MgSO on NLRP3 inflammasome expression in monocytes from 16 healthy non-pregnant women stimulated with monosodium urate (MSU). Monocytes were cultured in vitro with or without MSU and MgSO. Gene and protein expression of NLRP3, caspase-1, and gasdermin D were assessed by RT-qPCR and flow cytometry. The concentrations of IL-1β, IL-18, TNF-α, and IL-10 in culture supernatants were measured using ELISA. MSU stimulation increased the expression of NLRP3 and its components, confirming the activation of the inflammasome. Treatment with MgSO significantly reduced the expression of NLRP3, caspase-1, gasdermin D, IL-1β, and TNF-α, while increasing IL-10 levels. Additionally, MSU induced intracellular calcium elevation, whereas MgSO significantly decreased calcium concentration. These findings demonstrate that MgSO exerts an immunomodulatory effect on MSU-activated monocytes by downregulating NLRP3 inflammasome activation, pyroptosis, and proinflammatory cytokine production through a calcium-dependent mechanism. This suggests that MgSO may contribute to reducing the exaggerated inflammatory response associated with PE, supporting its therapeutic actions beyond seizure prevention.
ILT4 and its R20H variant as marker of poor prognosis in Spanish patients with colorectal cancer.
Fernández-Uría S, Vaquero-Yuste C, Álvarez-González E … +6 more , Del Pueblo CS, Suárez-Solís ML, Mugüerza-Huguet JM, Arnaiz-Villena A, Martín-Villa JM, Juarez I
Hum Immunol · 2026 Mar · PMID 41570702 · Publisher ↗
BACKGROUND: Immune checkpoint blockade is proving beneficial for cancer treatment by stimulating the anti-tumor immune response. However, the lack of success in certain cancer types encourages the research of new potenti...
BACKGROUND: Immune checkpoint blockade is proving beneficial for cancer treatment by stimulating the anti-tumor immune response. However, the lack of success in certain cancer types encourages the research of new potential targets. ILT4 (Immunoglobulin-like transcript 4) is a transmembrane protein that binds with high affinity to HLA-G molecules present on tumor cells, modulating responses mediated by monocytes, macrophages, and dendritic cells. OBJECTIVE: To compare ILT4 expression and the distribution of the LILRB2 rs383369 single nucleotide polymorphism (SNP), a R20H variant resulting in higher levels of ILT4 expression, in patients with colorectal adenocarcinoma of Spanish origin. METHODS: Seventy-three patients with colorectal adenocarcinoma were included in this study. ILT4 expression was assessed by immunohistochemistry and flow cytometry. Genotyping of the rs383369 SNP was performed by PCR-RFLP and further confirmed by Sanger sequencing. Associations were tested with clinical variables, histological differentiation, and survival outcomes. RESULTS: Flow cytometric analysis confirmed ILT4 expression in the peripheral blood mononuclear cells of patients with colorectal adenocarcinoma. Similarly, immunohistochemistry demonstrated a greater infiltrate of ILT4 + cells in tumor tissue samples compared to distal tissue. The frequency of the rs383369-C (20H) variant was increased in patients with lymph node infiltration, identifying the C allele as a risk variable for tumor progression towards nodal invasion and more severe disease (p-value = 0.035). CONCLUSIONS: Patients with colorectal tumors exhibit a high infiltrate of ILT4 + cells within the tumors, and the rs383369-C polymorphism is linked to greater pathological severity. These results support the involvement of ILT4 in the development of colorectal tumors, as well as its potential use as a biomarker and therapeutic target.
Characterization of anti-HLA antibodies pre- and post-renal transplantation in the Tunisian central region.
Changuel M, Bannour I, Elghali M … +7 more , Mahmoud NB, Chouat H, Jaafar I, Aissi W, Hamouda M, Skhiri H, Sakly N
Hum Immunol · 2026 Mar · PMID 41564752 · Publisher ↗
BACKGROUND: In kidney transplantation, anti-HLA antibodies are associated with poor graft outcomes. This study aimed to describe the profile of anti-HLA antibodies in both renal transplanted patients and patients awaitin...
BACKGROUND: In kidney transplantation, anti-HLA antibodies are associated with poor graft outcomes. This study aimed to describe the profile of anti-HLA antibodies in both renal transplanted patients and patients awaiting transplantation and to assess their impact on graft outcomes in the Tunisian central coastal region. METHODS: We retrospectively analyzed the results of anti-HLA antibody determination in 191 patients (31 transplanted and 160 awaiting transplantation) recruited between January 2019 and October 2024. Anti-HLA antibodies were investigated, prior and after a kidney transplantation if any, at the Immunology Laboratory of the University Hospital of Monastir, using Luminex technology in two steps: screening and single antigen typing. RESULTS: Among the 191 patients evaluated before transplantation, 31.4 % (60/191) had anti-HLA antibodies, and 12.9 % (4/31) developed de novo antibodies after transplantation. Among the sensitized individuals, 92.2 % had anti-HLA class I antibodies, 54.7 % had class II antibodies, and 46.9 % had antibodies against both classes. The most frequent specificities were anti-HLA A2, A25, B44, B45, DQ7, and DR17. Sensitization was significantly associated with a history of blood transfusion (42.0 %; p = 0.036). High immunization levels (cPRA > 80 %) were observed in 24.5 % of patients with class I antibodies and 29 % with class II antibodies, while high Mean Fluorescence Intensity (MFI > 10,000) were detected in 38.9 % and 58.1 % of class I and class II cases, respectively. After transplantation, de novo developed antibodies were non-donor-specific antibodies, except for one. Graft rejection occurred in four patients (12.9 %), comprising three acute cellular rejections and one chronic rejection. CONCLUSION: In summary, our study confirmed that anti-HLA antibodies are relatively frequent prior to transplantation. They are not associated with antibody-mediated rejection, and the most frequently detected antibody specificities did not correlate with the most prevalent HLA antigens in the Tunisian population.
HLA typing challenges in organ donation after transplant.
Lemp NA, Lalli P, Dionne SO
Hum Immunol · 2026 Mar · PMID 41564751 · Publisher ↗
BACKGROUND: Human leukocyte antigen (HLA) typing is essential for organ donor-recipient matching. However, complexities arise when donors have unique clinical histories that are not fully disclosed to laboratory personne...
BACKGROUND: Human leukocyte antigen (HLA) typing is essential for organ donor-recipient matching. However, complexities arise when donors have unique clinical histories that are not fully disclosed to laboratory personnel. CASE PRESENTATION: We describe two cases involving deceased organ donors who had recently received liver and lung transplants, respectively, prior to death. Both cases of Organ Donation After Transplant (ODAT) were referred for urgent infectious disease and HLA testing. In each case, HLA typing from peripheral blood specimens failed. At the time of laboratory submission, prior transplant status was not disclosed. OUTCOME: Buccal swabs and pre-transplant HLA typing were obtained to determine HLA typing for use in organ allocation. CONCLUSION: These cases underscore the need for timely, complete clinical communication between organ procurement teams and histocompatibility laboratories to avoid preventable delays and improve safety and efficiency in the donor allocation process.
A novel pathogenic RFXANK variant causing MHC class II deficiency in two unrelated patients from Mexico.
Nuñez-Nuñez ME, Valenzuela-Vazquez L, Bustamante-Ogando JC … +7 more , Bayardo-Gutierrez B, Lona-Reyes JC, Estrada-Arce EV, Martinez-Duncker I, Lugo-Reyes SO, Espinosa-Padilla SE, Cruz-Muñoz ME
Hum Immunol · 2026 Mar · PMID 41558066 · Publisher ↗
Abstract loading — click title to view on PubMed.
Association of NLRC3 gene polymorphism with Graves' disease susceptibility in a Southwest Chinese Han population.
Liang Z, Li Q, Wang X … +4 more , Sun X, Li H, Chen J, Yu H
Hum Immunol · 2026 Mar · PMID 41547091 · Publisher ↗
PURPOSE: Graves' disease (GD) is a frequently-occurring autoimmune thyroid condition, distinguished by complex molecular and cellular alterations. However, the fundamental mechanisms underlying its pathogenesis are still...
PURPOSE: Graves' disease (GD) is a frequently-occurring autoimmune thyroid condition, distinguished by complex molecular and cellular alterations. However, the fundamental mechanisms underlying its pathogenesis are still mostly unknown. The objective of this research was to explore the association between gene polymorphisms in candidate genes (NLRC3, SATB1 and USP19) and susceptibility to GD in a Southwest Chinese Han population. METHODS: A two-stage association analysis was conducted in 768 GD patients and 768 healthy controls. Genotyping of NLRC3 rs117213971 C > G, SATB1 rs2229261 G > T and USP19 rs11552724 C > G was performed using the Sequenom Massarray platform. Additionally, the expression of candidate genes was assessed using qRT-PCR, and inflammatory cytokines (IL-17, IL-10, and TGF-β1) levels were measured by ELISA. RESULTS: In the initial phase of statistical analysis, GD patients exhibited significantly higher frequencies of the NLRC3 rs117213971 C > G C allele and a greater prevalence of the CC genotype, a finding confirmed with a larger sample set. Additionally, the NLRC3 rs117213971 C > G CC genotype was significantly associated with increased IL-17 levels, decreased TGF-β1 secretion, and reduced NLRC3 expression. CONCLUSION: This study demonstrates a strong correlation between the NLRC3 rs117213971 C > G genotype and susceptibility to GD in the Southwest Chinese Han population, suggesting that NLRC3 expression regulation and inflammatory cytokine secretion may contribute to the development of GD.
Reuse of a living donor kidney: A case study.
Yin Y, Prewitt F, Nguyen J … +7 more , Tao J, Pham PT, Kendrick E, Nassiri N, Veale JL, Reed EF, Hickey MJ
Hum Immunol · 2026 Mar · PMID 41547090 · Publisher ↗
Reuse of a previously transplanted solid organ for another recipient prevents waste of functioning organs. Here, we present a case of a kidney transplant in which the donor had previously received a kidney from a living...
Reuse of a previously transplanted solid organ for another recipient prevents waste of functioning organs. Here, we present a case of a kidney transplant in which the donor had previously received a kidney from a living donor 6 years earlier. We discuss system inefficiencies and gaps that complicate clinical decision making in this context. For example, during allocation donor ID, KDPI and HLA typing misrepresent the kidney that is from a prior donor potentially confounding virtual crossmatching. In addition, samples of PBMC received from the donor are insufficient for physical crossmatching. As well, peri-operative and post-transplant management in this context requires assessment of donor specific antibodies to the current and prior donor.
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