Human Immunology[JOURNAL]
Sun
200 papers
In-silico design of a therapeutic multi-epitope peptide candidate vaccine against rheumatoid arthritis.
Mohammadi Sepahvand A, Azarbani N, Zare F … +2 more , Negahdaripour M, Dehshahri A
Hum Immunol · 2026 Mar · PMID 41529662 · Publisher ↗
Rheumatoid arthritis (RA) is a systemic autoimmune disease primarily affecting the joints, resulting in inflammation, swelling, and pain, ultimately impacting patients' quality of life and causing premature death. TNF-α,...
Rheumatoid arthritis (RA) is a systemic autoimmune disease primarily affecting the joints, resulting in inflammation, swelling, and pain, ultimately impacting patients' quality of life and causing premature death. TNF-α, regulated by the NF-κB transcription factor, is a key cytokine implicated in tissue destruction and disease progression. Both TNF-α and the NF-κB receptor ligand (RANKL) are considered significant targets in the treatment of RA. Due to the limitations of current therapeutic strategies in providing safe and effective long-term healing, there is a clear need for novel therapeutic interventions, including vaccine development. This study aims to design an innovative multi-epitope polypeptide vaccine targeting RA through computational methods. To achieve this goal, epitope sequences from TNF-α and RANKL were predicted using three servers. Adjuvants CTxB, PADRE, and B29 were then incorporated with appropriate linkers. The structure underwent several analyses to assess physicochemical properties, immunogenicity, and allergenicity using various servers. The designed protein showed slightly hydrophilic characteristics with a negative Gravy index and a pI of 8.20. Additionally, with an instability index below 40, the protein demonstrates stability, which is crucial for the vaccine's effectiveness. To predict the 3D structure, I-TASSER and trRosetta servers were utilized, and the best models underwent refinement using the GalaxyRefine server. Validation of the refined models was performed by the ProSA-web and Ramachandran plot analysis, and the best model was determined. Ultimately, the results of the conformational B-cell epitope prediction of the final model suggested that the designed vaccine can effectively trigger the humoral immune response. The combination of ten epitopes from TNF-α and RANKL linked with CTxB, PADRE, and B29 adjuvants presented a promising therapeutic candidate vaccine for RA.
Discerning the HLA allele and haplotype frequencies in the multiethnic population of Malaysia.
Kevin-Tey WF, Wen S, Chong HP … +8 more , Bee PC, Mohd Zain S, Mohamad M, Mohamed Yusoff N, Eng HS, Lim SK, Tan SM, Jalalonmuhali M
Hum Immunol · 2026 Feb · PMID 41512418 · Publisher ↗
The human leukocyte antigen (HLA) system is central to immune function, transplantation compatibility, and disease susceptibility. However, comprehensive data on HLA allele and haplotype distributions in Southeast Asia,...
The human leukocyte antigen (HLA) system is central to immune function, transplantation compatibility, and disease susceptibility. However, comprehensive data on HLA allele and haplotype distributions in Southeast Asia, particularly Malaysia, remain limited despite the region's rich genetic diversity. In this study we analyzed HLA class I (A, B, C) and class II (DRB1, DQB1) alleles in 4,882 individuals of Malay, Chinese, Indian, and Indigenous descent from genotyping data collected between 2000 and 2020. HLA genotyping was performed using PCR-SSP and PCR-SSO methods. Haplotype frequencies (HF) were resolved using haplotype segregation analysis (HSA) and the expectation-maximization (EM) algorithm, with linkage disequilibrium (LD) and Hardy-Weinberg equilibrium (HWE) evaluated across loci. The most frequent alleles included HLA-A*11, -A*02, -B*15, -B*40, -C*07, -C*03, -DRB1*15, and -DQB1*03, with notable variation among ethnic groups. A total of 1,416 unique A ∼ B ∼ DRB1 ∼ DQB1 haplotypes and 1,317 A∼C∼B∼DRB1∼DQB1 haplotypes were identified, with A*33∼C*03∼B*58∼DRB1*03∼DQB1*02 being the most prevalent overall (4.0 %). Ethnic-specific haplotypes were also delineated, underscoring the population's complex genetic architecture. Principal component analysis demonstrated genetic relatedness between Malaysian groups and other East and South Asian populations. This study represents the largest multiethnic HLA dataset in Malaysia to date. The findings contribute valuable insights for population genetics, donor registry optimization, and future disease association and immunogenomic research in Southeast Asia.
Potential synergistic role of pre-formed GSTT1 antibodies and de novo HLA antibodies in a heart-transplant recipient diagnosed with AMR.
Chitnis NS, Nunugonda M, Foye C … +6 more , Erice PA, Robinson PJ, Cortes-Santiago N, Kearney DL, Spinner JA, Jindra PT
Hum Immunol · 2026 Feb · PMID 41506028 · Publisher ↗
Our center had a case of a 20-year old female with severe bi-ventricular dysfunction, leading to heart transplantation. Strong GSTT1 antibody was detected pre-transplant, which encouraged us to further study its possible...
Our center had a case of a 20-year old female with severe bi-ventricular dysfunction, leading to heart transplantation. Strong GSTT1 antibody was detected pre-transplant, which encouraged us to further study its possible significance. Glutathione S-transferases (GSTs) are a class of enzymes that metabolize xenobiotics. We hypothesized that high-titer non-HLA antibodies to GSTT1 can be generated in recipients who have a complete GSTT1 gene deletion and are exposed to GSTT1 antigen. When a donor organ is transplanted, the anti-GSTT1 antibodies could bind to functional GSTT1 which has been exposed due to transplant-related injury and contribute to allo-rejection. We genotyped GSTT1 with Real-Time PCR along with antibody screening using both HLA and non-HLA panels and found this recipient had a null GSTT1 genotype. Pre-transplant serum showed significantly high GSTT1 antibody. One-year post-transplant, there was an abnormal biopsy with antibody-mediated rejection (AMR) detected by microscopy and molecular profiling, showing both intra-luminal mononuclear cells as well as plasma cells, an atypical infiltrate. There were low levels of de novo DQ8 antibodies within the first year, that rose to moderate levels two years later with accompanying de novo moderate levels of DQ6 antibodies. Following AMR treatment, the GSTT1 Ab level decreased. Follow up testing showed increased inflammation and AMR by molecular profiling at 28 months post-transplant. The patient developed worsening cardiac allograft vasculopathy (CAV) and ultimately required re-transplantation.
HLA-E gene polymorphism and expression in colorectal cancer patients.
Dhouioui S, Boujelbene N, Hasni M … +9 more , Mansouri H, Bourogâa H, Jalouli M, Mokrani A, Mchiri R, Harrath AH, Zemni I, Rebmann V, Zidi I
Hum Immunol · 2026 Feb · PMID 41481968 · Publisher ↗
HLA-E has been proposed as an immunomodulatory molecule in various physiological and pathological contexts. However, few data are available on its involvement in bowel oncogenesis. Our aim was to investigate whether HLA-...
HLA-E has been proposed as an immunomodulatory molecule in various physiological and pathological contexts. However, few data are available on its involvement in bowel oncogenesis. Our aim was to investigate whether HLA-E gene polymorphism and its expression as soluble molecules (sHLA-E) contribute to colorectal cancer (CRC) pathology in the Tunisian population. A total of 240 CRC patients and 254 age/gender-matched healthy controls (CTRLs) were genotyped for HLA-E*01:01/01:03 polymorphism (rs1264457) using sequence-specific-primers (PCR-SSP). sHLA-E levels in plasma samples (50 CRC patients and 97 CTRLs) were measured by Enzyme linked ImmunoSorbent assay (ELISA). Our results revealed lower frequencies of the HLA-E*01:01 allele (OR = 0.70, 95 %CI = [0.55-0.90], p = 0.005) and HLA-E*01:01/01:01 homozygous genotype (OR = 0.55, 95 %CI = [0.36-0.85], p = 0.005) in CRC patients compared to CTRLs. Furthermore, individuals with HLA-E*01:01 are less likely to develop CRC before the age of 50. After stratifying the patients and CTRLs by gender, it became evident that frequencies of HLA-E*01:03 allele (p = 0.001) and HLA-E*01:03/01:03 genotype (p = 0.004) were significantly higher in female patients compared to female CTRLs. However, Kaplan-Meier survival analysis showed that female patients carrying the HLA-E*01:01 (N = 82) displayed a significant shorter 3-year overall survival (HR = 2.37; 95 % CI = [1.15-4.85], p = 0.01) than non-carriers (N = 37). Additionally, sHLA-E levels in patients were significantly (p = 0.006) reduced in females (1.8 ng/ml) compared to males (2.6 ng/ml). No relationship between sHLA-E levels and HLA-E polymorphism was found. Further, there was no significant association between sHLA-E levels and CRC outcome although enriched sHLA-E molecules were able to downregulated T cells mediated IFN-γ production in a dose-independent manner. Overall, these data suggest that in the Tunisian population, HLA-E*01:01/01:03 gene polymorphism and circulating sHLA-E molecules in female CRC patients may be important factors enabling gender-specific strategies for the diagnosis and treatment of this cancer.
Recovery from post-renal transplant lymphopenia predicts graft function and survival.
Eappen K, Morrissey P, Heffernan DS
Hum Immunol · 2026 Feb · PMID 41422733 · Publisher ↗
Renal transplantation remains the gold standard for treating end-stage renal disease, yet early identification of patients at risk for graft dysfunction is essential to improving outcomes. Lymphocytes play a key role in...
Renal transplantation remains the gold standard for treating end-stage renal disease, yet early identification of patients at risk for graft dysfunction is essential to improving outcomes. Lymphocytes play a key role in the immune response and transplant rejection. Fluctuations in postoperative lymphocyte counts may arise from surgical stress and immunosuppression. We conducted a retrospective study of prospectively collected data with 376 consecutive adult renal transplant recipients at a single center from 2015 to 2023. Lymphopenia was observed after kidney transplantation with nadir on post-operative day (POD) 3 and gradual recovery by POD5. Multivariable analysis revealed that POD5 lymphocyte count < 0.5x10 cells/L was associated with increased odds of acute rejection (OR = 2.97;p = 0.037). Rapid recovery from lymphopenia on POD3 to POD5 predicted lower odds of delayed graft function (OR = 0.38;p = 0.047), and delayed recovery from POD3 to POD4 predicted higher risk of 3-year graft failure (OR = 5.23; p = 0.025). These findings suggest that early lymphocyte trends may serve as accessible, clinically relevant biomarkers for graft prognosis following renal transplantation.
Prolonged wait times among highly sensitized HLA-B46 homozygous kidney transplant candidates.
Butler CL, Gragert L, Du A … +17 more , Yin Y, Pulido MA, Elsheikh NE, Choi SM, Hickey MJ, Zhang QJ, Timofeeva O, Reed EF, Shaikh SJ, Gandhi M, Chen LX, Goussous N, Alexopoulos S, Perez R, Sageshima J, Huang Y, Sosa RA
Hum Immunol · 2026 Feb · PMID 41420996 · Publisher ↗
BACKGROUND: Individuals who are homozygous for HLA-B46 lack shared epitopes with most other HLA-B antigens and are capable of developing antibodies against all non-self B antigens including Bw4 and Bw6 epitopes. We ident...
BACKGROUND: Individuals who are homozygous for HLA-B46 lack shared epitopes with most other HLA-B antigens and are capable of developing antibodies against all non-self B antigens including Bw4 and Bw6 epitopes. We identified a series of B46 homozygous kidney transplant candidates with long wait times and high cPRAs. METHODS: A retrospective observational analysis was conducted on HLA typing and antibody profiles of deceased donor kidney waitlist candidates at the University of California, Davis. Waiting times among calculated panel reactive antibody (cPRA) and sex subgroups were compared using one-way ANOVA. RESULTS: Among 1,772 waitlist candidates, we found seven that were B46-homozygous (all Asian, four females, three males), with three of the seven having cPRAs > 99.98%. The median wait time for the four females was 4,654 days. The highly-sensitized B46 female subgroup had significantly longer waiting times than males (median 1,071 days) and for all other > 99.50% cPRA patients (median 2,299 days). CONCLUSIONS: These highly-sensitized B46 homozygous candidates had a very small pool of HLA-compatible donors and experienced extremely long waiting times. Future studies are needed using registry data to confirm these findings and assess outcomes.
Study of the association of LILRB2 gene polymorphisms with colorectal cancer susceptibility and prognosis in Tunisian population.
Ferjani M, Dhouioui S, Bourogâa H … +6 more , Jalouli M, Boujelbene N, Zemni I, Harrath AH, Ayadi MA, Zidi I
Hum Immunol · 2026 Feb · PMID 41418557 · Publisher ↗
BACKGROUND: leukocyte immunoglobulin-like receptors subfamily B member 2 (LILRB2), a receptor with immunosuppressive properties belonging to the Leucocytes Ig-Like receptors (LILR) family, is extensively detected in vari...
BACKGROUND: leukocyte immunoglobulin-like receptors subfamily B member 2 (LILRB2), a receptor with immunosuppressive properties belonging to the Leucocytes Ig-Like receptors (LILR) family, is extensively detected in various tumor tissues. Its major ligand, human leukocyte antigen G (HLA-G), is pivotal in enabling tumor immune escape. This study sought to investigate the potential impact of LILRB2 gene polymorphisms (rs383369 G > A and rs7247538 C > T) on colorectal cancer (CRC) susceptibility and prognosis in the Tunisian population. METHODS: Genotyping of the LILRB2 gene polymorphisms rs7247538 C > T and rs383369 G > A was performed by PCR-RFLP. A total of 141 CRC patients and 150 healthy controls were included in this case-control study. RESULTS: The rs7247538 C allele and C/C genotype were found to be significantly more prevalent in healthy controls compared to CRC patients (p = 0.008 and p = 0.012, respectively). Furthermore, the C allele was more prevalent in the control subgroup above 50 years compared to CRC patients (p = 0.033). The rs383369 A/A genotype showed a significantly higher prevalence in controls than in CRC patients (p = 0.025). The rs383369 A/G genotype was significantly associated with a higher risk of CRC susceptibility in both the overall study population (p = 0.006) and in patients diagnosed after the age of 50 years (p = 0.014). The concomitant occurrence of both C and A alleles could provide a protective effect against CRC development (p = 0.003). CONCLUSION: The study indicates that LILRB2 SNPs are associated with susceptibility to CRC within the Tunisian population. These results underscore the relevance of LILRB2 SNPs as important biomarkers in CRC, potentially paving the way for the design of new personalized therapies guided by genetic profiles.
Increasing the liver donation pool: Eculizumab desensitization for ABO-incompatible living donor liver transplantation - A case series.
Spaggiari M, Alaniz MJ, Kortan E … +8 more , Valdepenas B, Benken J, Gaitonde S, Kim H, Chalisa A, Atia LG, Benedetti E, Tzvetanov I
Hum Immunol · 2026 Feb · PMID 41411792 · Publisher ↗
INTRODUCTION: ABO-incompatible living donor liver transplantation (ABO-I LDLT) is limited by the risk of antibody-mediated rejection (AMR) from preformed anti-A/B antibodies. Conventional desensitization with therapeutic...
INTRODUCTION: ABO-incompatible living donor liver transplantation (ABO-I LDLT) is limited by the risk of antibody-mediated rejection (AMR) from preformed anti-A/B antibodies. Conventional desensitization with therapeutic plasma exchange (TPE) and rituximab (RTX) has procedural and logistical drawbacks. METHODS: We conducted a retrospective analysis of patients who underwent ABO-I LDLT at our center between January 2022 and December 2023. All were managed with eculizumab (ECU) at a dose of 900 mg IV on preoperative day - 1 and again within two weeks, without preoperative TPE or RTX. RESULTS: Median recipient age was 49.5 years (MELD 14). All achieved prompt graft function. No biopsy-proven AMR was identified in the patients in whom biopsy was performed. Complement activity normalized by POD 30 in all cases. At a mean follow-up of 17 months, three patients had stable graft function; one died at one year from a cerebrovascular event unrelated to rejection. CONCLUSION: ECU-based complement inhibition may offer a simplified, potentially AMR-reducing approach in ABO-I LDLT; these findings are preliminary and hypothesis-generating, requiring validation in larger studies.
Pleiotropic gene mapping reveals shared immune regulatory hubs across 15 autoimmune diseases.
Jin Y, Lu HM, Yu XH
Hum Immunol · 2026 Feb · PMID 41406704 · Publisher ↗
BACKGROUND: Autoimmune diseases (AIDs) involve immune dysfunction with complex genetic underpinnings. This study examined genetic correlations and directional genetic associations across 15 AIDs to identify common immune...
BACKGROUND: Autoimmune diseases (AIDs) involve immune dysfunction with complex genetic underpinnings. This study examined genetic correlations and directional genetic associations across 15 AIDs to identify common immune pathways. METHODS: We retrieved GWAS summary statistics for 15 AIDs and analyzed genetic overlap using LDSC and Z-score correlations. Pleiotropy was assessed via MAGMA to assign SNPs to genes and PLACO for pleiotropic gene detection. Functional annotation (FUMA) and pathway enrichment (MAGMA, MSigDB) were performed. Two-sample Mendelian randomization (MR) explored causal links between diseases and immune cell traits. RESULTS: Primary Biliary Cholangitis (PBC) had the highest SNP-heritability (43.3 %), followed by Systemic Lupus Erythematosus (SLE) (32.84 %). Most disease pairs showed positive genetic correlations. We identified 76 pleiotropic genes, with HCP5, NOTCH4, and SKIV2L shared across all 15 diseases and concentrated in the extended MHC region. Enrichment analysis highlighted cytokine signaling, antigen presentation, and T-cell-mediated pathways. MR revealed directional genetic associations among rheumatoid arthritis (RA), SLE, and Systemic Sclerosis (SS), with PBC increasing SLE risk (OR = 1.253) and Inflammatory Bowel Disease (IBD) slightly protecting against Type 1 Diabetes (T1D) (OR = 0.959). Cell-type MR showed SKIV2L acting across multiple T-cell and myeloid subsets, whereas NOTCH4 effects were confined to M2 macrophages, highlighting distinct MHC-region hubs with broad versus myeloid-focused impact. CONCLUSION: These findings map shared genetic components and highlight pleiotropic genes, especially SKIV2L, HCP5 and NOTCH4, linking extended-MHC architecture to T-cell and myeloid programs. They provide a genetic framework for prioritizing common pathways and cell types for biomarker development and targeted therapy.
Better pancreatic adenocarcinoma outcomes linked to anti-EBV TCR CDR3 detection via tumor RNAseq files.
Baker MC, Paul S, Lewis GV … +5 more , Goel N, Huda TI, Singh T, Song JJ, Blanck G
Hum Immunol · 2026 Feb · PMID 41401737 · Publisher ↗
Although the Epstein-Barr virus (EBV) is implicated in several cancer types, its potential role in the initiation and progression of pancreatic cancer remains poorly understood. In this study, T-cell receptor (TCR) compl...
Although the Epstein-Barr virus (EBV) is implicated in several cancer types, its potential role in the initiation and progression of pancreatic cancer remains poorly understood. In this study, T-cell receptor (TCR) complementarity-determining region 3 (CDR3s) were isolated from tumor-derived RNAseq files of two independent pancreatic adenocarcinoma datasets. Patients found to have exact matches to anti-EBV TCR CDR3s exhibited better overall and disease-free survival across both datasets. For example, for one dataset: 91 cases positive for anti-EBV TCR CDR3s had a median overall survival (OS) of 22.27 months versus 43 cases negative for anti-EBV CDR3s, with a median OS of 14.95 months (logrank p-value = 0.0195). Expression of immune marker genes representing T-cell functions were significantly higher in cases with anti-EBV TCR CDR3s, consistent with a potential role for enhanced anti-viral immune activity in these patients. These findings also suggest that several immune marker genes studied in this report could serve as novel biomarkers for pancreatic adenocarcinoma and may hold clinical value for prognoses. Additionally, genomic anomaly assessments revealed that anti-EBV CDR3-positive samples had significantly lower mutation counts, consistent with a greater role for EBV in supporting the development of pancreatic adenocarcinoma than previously recognized. The findings justify consideration of assessments of EBV status and tumor mutation burdens for patient stratification. Also, EBV-targeted immunotherapy for pancreatic adenocarcinoma may be considered for clinical trials.
Belatacept suppresses B-cell subset alloresponses.
Ashokkumar C, Townsend R, Roberts M … +5 more , Thomas L, Gavin B, Spishock B, Higgs BW, Sindhi R
Hum Immunol · 2026 Jan · PMID 41380467 · Publisher ↗
BACKGROUND: Belatacept-treated kidney transplant recipients (KT) experience a lower incidence of de novo donor-specific anti-HLA antibody (DSA) formation despite their higher risk of acute cellular rejection. In vitro st...
BACKGROUND: Belatacept-treated kidney transplant recipients (KT) experience a lower incidence of de novo donor-specific anti-HLA antibody (DSA) formation despite their higher risk of acute cellular rejection. In vitro studies show that concentrations associated with half-maximal suppression (EC50) of target cells correlate with therapeutic trough concentrations (C0). PURPOSE: To determine whether belatacept inhibits B-cell alloantigen presentation and B-cell alloresponse at known therapeutic C0. METHODS: Peripheral blood leukocytes (PBL) from healthy adults were cultured with HLA-mismatched PBL or fluorochrome-labeled alloantigenic lysate and increasing belatacept concentrations. EC50 was calculated with best-fit four-parameter log-logistic function under a Poisson assumption, as described. RESULTS: After overnight allostimulation, frequencies of alloreactive CD154 + B-cells and their subsets decreased with increasing belatacept concentrations (n = 10). Median (range) EC50s were 1.3 (0.01-37) µg/ml for unfractionated B-cells, 2 (0.03-50) µg/ml for naïve, 3.6 (0.2-92) µg/ml for unswitched memory, 6.2 (0.05-32) µg.ml for transitional, and 7.8 (0.01-101) µg/ml for plasmablasts. Median EC50s were highest at 19 and 31 µg/ml, respectively for CD27- and CD27 + isotype-switched memory B-cells. No effect was seen on B-cell presentation of alloantigen. CONCLUSIONS: At lower C0 levels of < 10 µg/ml, belatacept suppresses alloresponses of B-cells and most B-cell subsets, thereby explaining lower levels of DSA in kidney transplant patients.
Immunoglobulin γ allotypes influence the level of autoantibody responses to amyloid-β in patients with Alzheimer's disease.
Pandey JP, Kimball C, Nietert PJ … +2 more , Lah JJ, Levey AI
Hum Immunol · 2026 Jan · PMID 41371042 · Full text
Immunoglobulin GM (γ marker) allotypes, highly polymorphic hereditary antigenic determinants of IgG, have been shown to be a risk factor for the development of Alzheimer's disease (AD). The mechanisms underlying the GM-A...
Immunoglobulin GM (γ marker) allotypes, highly polymorphic hereditary antigenic determinants of IgG, have been shown to be a risk factor for the development of Alzheimer's disease (AD). The mechanisms underlying the GM-AD association are not understood. The aim of the present investigation was to determine whether GM genotypes influenced the level of naturally occurring antibodies to amyloid-β (Aβ), a hallmark of AD. We genotyped 100 AD cases and 100 controls for several GM alleles and measured antibodies to Aβ. Results showed that IgG1 GM 3/17 and IgG2 GM 23 genotypes were significantly associated with anti-Aβ antibody levels in AD cases (p = 0.014, 0.018, respectively), but not in controls (p = 0.62, 0.08, respectively). These results, for the first time, show GM allotype restriction in naturally occurring antibody responses to Aβ in individuals with AD. If confirmed, they could help devise a more potent Aβ-based immunotherapy against this neurogenerative disorder.
Allele-specific HLA-B39 antibody reactivity in a highly-sensitized kidney transplant candidate.
Du A, Ishaq W, Flores DA … +9 more , Saquilayan M, Ling C, Muramoto J, Kendall K, Butler CL, Reed EF, Zhang QJ, Barba LM, Sosa RA
Hum Immunol · 2026 Jan · PMID 41371041 · Publisher ↗
A 43-year-old highly sensitized female waitlisted over 16 years received a deceased donor kidney offer. Virtual crossmatch (VXM) revealed three historic donor-specific antibodies (DSA) against the potential donor. Additi...
A 43-year-old highly sensitized female waitlisted over 16 years received a deceased donor kidney offer. Virtual crossmatch (VXM) revealed three historic donor-specific antibodies (DSA) against the potential donor. Additionally, the patient appeared to have strong current allele-specific DSA to HLA-B*39:01 based on positive reactivity by single antigen bead (SAB) testing and self-typing of B*39:08. The donor was typed B39 homozygous by real-time PCR (RT-PCR) by an outside laboratory with the allele-string including B*39:02/05/08/13. B*39:01 is the only bead representing B39 antigen group in the main SAB panel from One Lambda. Allelic differences suggested potential differential reactivity. PXM yielded a negative result. Investigation into the reactivity using alternate bead panels, surrogate flow cytometry crossmatching and high-resolution HLA typing showed the confirmed allele-specific B*39:01 antibody cross-reacts with B*39:04/05/06 and does not react with B*39:02/08/13. This case underscores the need for enhanced VXM tools and workflows integrating expanded antibody panels and high-resolution typing.
Citrullinated vimentin and alpha enolase are expressed at the cell surface of apoptotic human neutrophils.
Morin-Genest J, Girard D
Hum Immunol · 2026 Jan · PMID 41365250 · Publisher ↗
The cytoskeletal vimentin (Vim) and the alpha-enolase (ENO1) proteins are associated with autoimmune and inflammatory diseases. We previously documented that Vim is degraded by caspases and expressed at the cell surface...
The cytoskeletal vimentin (Vim) and the alpha-enolase (ENO1) proteins are associated with autoimmune and inflammatory diseases. We previously documented that Vim is degraded by caspases and expressed at the cell surface of human apoptotic neutrophils. The aim of the present study was to monitor the expression of Vim, ENO1, and their citrullinated forms (cit-Vim, cit-ENO1) during the regulation of spontaneous human neutrophil apoptosis (SA) by the antiapoptotic cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) and the proapoptotic anti-cancer drug arsenic trioxide (ATO). Although the degradation of Vim during SA was delayed by GM-CSF and accelerated by ATO, no significant degradation of cit-Vim, ENO1, and cit-ENO1 was observed. However, Vim, ENO1, cit-Vim, and cit-ENO1 are expressed at the cell surface of apoptotic neutrophils. These data further support the potential participation of neutrophils in autoimmune and inflammatory diseases as they might be an important source of autoantigens when they undergo apoptosis.
Immunogenetr: A comprehensive toolkit for clinical HLA informatics.
Coskun B, Brown NK
Hum Immunol · 2026 Jan · PMID 41344288 · Publisher ↗
There is significant interest in using modern informatics processes for clinical HLA data, but there are few resources developed for clinical use. To help clinical HLA laboratories make use of best practices in informati...
There is significant interest in using modern informatics processes for clinical HLA data, but there are few resources developed for clinical use. To help clinical HLA laboratories make use of best practices in informatics and align with published data standards, we developed immunogenetr for the R programming language. immunogenetr was built with tidyverse functions and principles, and uses Genotype List (GL) string, which encodes complete HLA genotypes, including ambiguities, in a single human- and machine-readable object, as the primary data structure. The package includes functions to easily convert HLA genotyping data to and from GL strings, parse and rebuild GL strings, validate and truncate allele names, search for specific alleles within a GL string, and perform matching and mismatching. The functions are highly customizable, with matching and mismatching functions including options for host-versus-graft, graft-versus-host, and bidirectional comparisons, along with configurable homozygous mismatch counting, aligned with published guidelines. The package is open-source and available on CRAN and GitHub. This manuscript gives an overview of immunogenetr, with examples of how the functions can be used in informatics pipelines. Together, this package enables standardized HLA informatics analyses across clinical and research workflows.
Association of PD-1 (rs36084323) gene polymorphism with autoimmune thyroid diseases.
Elkady NM, Elzeiny AA, Abd El-Raouf MA … +4 more , Elzeiny D, El-Morsy BZ, Mohamed SZ, Nassar DK
Hum Immunol · 2026 Jan · PMID 41337788 · Publisher ↗
Autoimmune thyroid disease (AITD) is among the most common autoimmune diseases, including Graves' disease (GD) and Hashimoto's thyroiditis (HT), but their pathophysiological mechanism isn't fully understood with multiple...
Autoimmune thyroid disease (AITD) is among the most common autoimmune diseases, including Graves' disease (GD) and Hashimoto's thyroiditis (HT), but their pathophysiological mechanism isn't fully understood with multiple involved genetic factors. Programmed cell death-1 (PD-1) boosts the suppression of regulatory T cells. The promoter region polymorphism rs36084323 affected PD-1 gene transcription and activation in many cancer and autoimmune diseases. Genetic correlation between this polymorphism and AITD pathogenesis was evaluated in Egyptian patients & included: Group 1; fifty-five GD patients & forty five HT patients, Group 2; one hundred fifty controls by PCR-RFLP technique. GD patients showed significantly higher AG, AA, and A allele frequencies of the PD-1 rs36084323 gene than the control group with no significant disparities between HT patients and controls for any genotype or allele. When analyzing all AITD patients compared to control group, only the A allele showed higher frequency approaching statistical significance (p = 0.057). AA genotype and elevated free T4 were significant risk factors for GD, while elevated TSH was a significant protective factor for GD and a significant risk factor for HT. PD-1 rs36084323 polymorphism differs between GD and HT and is associated with higher risk of GD in Egyptian patients.
Bridging the gap: Correlating virtual crossmatch assessments with post-transplant immunologic outcomes.
Amato-Menker CJ, Lewis N, Paulus A … +4 more , Seelam S, Tchoukina I, Gupta G, Philogene MC
Hum Immunol · 2026 Jan · PMID 41317489 · Publisher ↗
The virtual crossmatch (VXM) is a widely implemented tool for assessing immunological risk using donor HLA typing and a recipient's antibody profile. Several studies have documented the efficacy and advantages of the VXM...
The virtual crossmatch (VXM) is a widely implemented tool for assessing immunological risk using donor HLA typing and a recipient's antibody profile. Several studies have documented the efficacy and advantages of the VXM. Most studies validate the accuracy of the VXM by showing correlation with flow crossmatch (FXM) results. However, true utility lies in correlation with transplant outcome and humoral immune response. In this study, we compared the VXM assessment, reported as VXM acceptable or unacceptable, to post-transplant outcome, donor-specific antibody development or resurgence, and FXM results. Overall, a VXM that was deemed acceptable correlated with fewer post-transplant adverse events compared to a VXMunacceptable. Kidney recipients with VXM unacceptable were significantly more likely to demonstrate memory HLA-DSA (p = 0.019), develop antibody-mediated rejection (AMR, p = 0.020), and develop AMR associated with HLA-DSA (p = 0.006) compared to kidney recipients with acceptable VXMs. Heart recipients showed similar trends although the results were not statistically significant due to small size. 94.4 % of VXM acceptable were also negative on FXM, and only 1.1 % of patients with acceptable VXMs benefited from a retrospective FXM. Our findings support the VXM as a reliable alternative to the FXM in most cases and identify situations where the FXM remains beneficial.
Xenotransplantation: From research to trial to practice.
Platt JL, Cascalho M
Hum Immunol · 2026 Jan · PMID 41317488 · Publisher ↗
Animals have been considered potential sources of organs and complex tissues for clinical transplantation, and occasional cross-species transplants have been performed (when human sources were scarce or unavailable) over...
Animals have been considered potential sources of organs and complex tissues for clinical transplantation, and occasional cross-species transplants have been performed (when human sources were scarce or unavailable) over the past 120 years. However, no clinical xenotransplant has been deemed successful. Today, after extensive efforts to understand the immunological and biological barriers to xenotransplantation and with the application of genetic engineering and other technologies to overcome these barriers, enthusiasm for xenotransplantation has grown again. A small number of clinical xenotransplants have recently been performed, with formal clinical trials either planned or underway. Therefore, it is important to consider whether and how clinical xenotransplantation might move forward. The key to advancing xenotransplantation from research to clinical practice depends on the experience gained-specifically, whether large clinical trials are necessary to prove feasibility and usefulness, or if such proof must be established before initiating large trials. This question prompted the development and publication of a collection of papers in Human Immunology in 2023. With the outcomes of a few clinical xenografts now known, the question is even more relevant. Consequently, an updated commentary and the contents of the collected papers follow.
HLA-B27 modulates the composition of the gut microbiota and drives a proinflammatory intestinal microecology.
Zhang T, Chen SY, Zhang C … +9 more , Chen R, Zhou PF, Li ZC, He Q, Fu XH, Wen W, Zhang CP, Yao MY, Geng JJ
Hum Immunol · 2026 Jan · PMID 41274275 · Publisher ↗
The pathogenesis of autoimmune diseases such as spondyloarthritis (SpA), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD) involves genetic factors and gut microbiota dysbiosis, which have been widely repor...
The pathogenesis of autoimmune diseases such as spondyloarthritis (SpA), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD) involves genetic factors and gut microbiota dysbiosis, which have been widely reported in patients and animal models. Although genetic factors are known to reshape the gut microbiota, the mechanistic role of the host gene-reshaped gut microbiota in mediating inflammatory diseases remains poorly characterized. This study focused on HLA-B27 to investigate its impact on the gut microbial composition and its association with HLA-B27 related autoimmune inflammatory diseases. The expression of HLA-B27/β2M significantly altered the diversity of the gut microbiota in mice, leading to changes in bacterial species and their functions. Concurrently, HLA-B27/β2M profoundly modified the gut metabolic profile, resulting in increased levels of multiple prostaglandins and decreased levels of anti-inflammatory metabolites. Multi-omics integrated analysis demonstrated that HLA-B27/β2M promoted the synthesis of Gram-negative bacteria while suppressing Gram-positive bacteria, findings validated in both omics datasets. Further validation confirmed that these HLA-B27/β2M-driven alterations in the gut microbial composition caused a shift toward a proinflammatory microbial community. These findings first revealed that genetic factors significantly reshaped the gut microbiota composition and further drove the microbial ecosystem toward a proinflammatory state. This study provides a foundation for identifying gut microbial signature targets in HLA-B27 associated diseases.
In silico identification of novel vaccine candidates against multidrug-resistant pseudomonas aeruginosa using subtractive proteomics and immunoinformatics.
Al-Harbi AI, Alshabrmi FM, Alatawi EA … +1 more , Fatima I
Hum Immunol · 2025 Nov · PMID 41265053 · Publisher ↗
Pseudomonas aeruginosa, a notorious pathogen, frequently presents in hospitals and poses numerous health issues due to its drug resistance, making treatment challenging. The rise of multidrug-resistant microorganisms emp...
Pseudomonas aeruginosa, a notorious pathogen, frequently presents in hospitals and poses numerous health issues due to its drug resistance, making treatment challenging. The rise of multidrug-resistant microorganisms emphasizes the crucial need for novel therapeutic approaches, such as vaccines. This work employed immunoinformatics and subtractive proteomics to find possible universal vaccine candidates. After analyzing the proteome of P. aeruginosa (PAO1 strain), three pathogenic or antigenic proteins were identified as potential targets for vaccines. T and B cell epitopes were predicted from vaccine candidate proteins using various immunoinformatics techniques. A vaccine was developed using specific epitopes (three Helper T lymphocyte (HTL), four Linear B lymphocyte (LBL), and seven Cytotoxic T lymphocyte (CTL) epitopes) and linkers, and a Cholera toxin subunit B adjuvant was added to enhance the immune response. The vaccine binds to and interacts with MHC molecules and TLR4 using molecular dynamics simulations and docking studies. After cloning, we reverse-translated the vaccine in E. coli to optimize protein production. Our approach offers a promising strategy for developing effective, long-lasting vaccines against Pseudomonas aeruginosa infections, which could help address the growing problems of antibiotic resistance in this bacterium.
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