Human Immunology[JOURNAL]
Sun
200 papers
Positive crossmatch with persistent donor specific antibodies increases risk of rejection in liver transplantation: A retrospective single-center analysis.
Corello H, Gimferrer I, Perkins J … +2 more , Kling CE, Henderson M
Hum Immunol · 2025 Jul · PMID 40280809 · Publisher ↗
Evidence is mixed regarding the effect of positive crossmatch (XM) and preformed donor-specific antibodies (DSA) on rejection in liver transplant recipients. We categorized liver transplant recipients by XM and DSA statu...
Evidence is mixed regarding the effect of positive crossmatch (XM) and preformed donor-specific antibodies (DSA) on rejection in liver transplant recipients. We categorized liver transplant recipients by XM and DSA status (XM negative, XM positive with resolved DSA, and XM positive with persistent DSA or any de novo DSA) and examined biopsy-proven rejection incidence within 6 months post-transplant, DSA trends, and immunosuppression management. Of 273 liver transplant recipients, 237 (86.8 %) were XM negative and 36 (13.2 %) were XM-positive, of whom 13 (36.1 %) had persistent or de novo DSA and 23 (63.8 %) had resolved DSA. Recipients in the persistent DSA group experienced earlier rejection at a higher rate (69.2 % at median of 25 days post-transplant) compared to the other two groups (21.7 % at median of 31 days in the resolved DSA group and 19.4 % at median of 46 days in the XM negative group; p < 0.001). Recipients in the persistent DSA group were also more likely to experience multiple rejection events (p < 0.001). XM positive recipients with persistent DSA or de novo DSA are at higher risk for early allograft rejection, while those who can clear their DSA early have a rejection risk profile similar to recipients with a negative crossmatch.
UCN expresses differently in left-sided and right-sided colon cancer contributing to distinct immune microenvironment via regulating CCL23.
Xiong Z, Hu L, Peng H … +4 more , Jiang X, Wang X, Tu L, Xu S
Hum Immunol · 2025 Jul · PMID 40274491 · Publisher ↗
PURPOSE: Urocortin (UCN), is found to be overexpressed in colorectal cancer (CRC) but its role in tumor immune microenvironment (TIME) remains unclear. METHODS: UCN expression was analyzed using RNA sequencing data from...
PURPOSE: Urocortin (UCN), is found to be overexpressed in colorectal cancer (CRC) but its role in tumor immune microenvironment (TIME) remains unclear. METHODS: UCN expression was analyzed using RNA sequencing data from TCGA and detected in tumor samples from 18 patients with LC and 27 patients with RC. Tumor infiltrated T cells (TILs) were isolated from tumors and the exhaustion markers including PD-1, TIGIT, TIM-3 and LAG3 on CD8 + TILs were detected by flow cytometry. Correlations between UCN level and immunoregulatory factors were analyzed using Spearman correlation analysis. UCN was overexpressed in CRC cell lines and the CCL23 levels were detected by quantitative RT-PCR and enzyme-linked immunosorbent assay. RESULTS: UCN was mainly overexpressed in Right-sided colon cancer (RC) and to be related to poor prognosis. Higher UCN level in tumors related to increased abundance of regulatory T cells and upregulated exhaustion markers in CD8 + T cells. UCN is positively correlated with CCL23 level in CRC and mainly upregulated in RC samples. Overexpression of UCN in HCT116 and HT-29 cells upregulated CCL23 expression and promoted CCL23 secretion. CD8 + T cells cultured with medium from UCN overexpressed CRC cells exhibited exhaustion phenotype with increased expression of CTLA-4, PD-1, TIGIT, TIM-3 and LAG-3, which was restored by CCL23 antibody. CONCLUSION: This study successfully constructed the correlation between UCN overexpression and immunosuppressive TIME formation in CRC, providing a candidate target for new immunotherapy against CRC development.
Single-cell analysis unveils immune dysregulation and EBV-driven lymphoproliferative disorder in pediatric liver transplant recipients.
Wen Y, Chen C, Zhou T … +3 more , Liu C, Zhang Z, Gu G
Hum Immunol · 2025 Jul · PMID 40263002 · Publisher ↗
Post-transplant lymphoproliferative disorder (PTLD) is a severe complication following liver transplantation, particularly in pediatric patients, with a high incidence rate associated with Epstein-Barr virus (EBV) infect...
Post-transplant lymphoproliferative disorder (PTLD) is a severe complication following liver transplantation, particularly in pediatric patients, with a high incidence rate associated with Epstein-Barr virus (EBV) infection. The immunological microenvironment of PTLD, particularly the cellular and molecular changes associated with EBV infection, remains unclear. Using scRNA-seq, we examined changes in the immune microenvironment of PBMC from pediatric liver transplant recipients across four groups: PTLD patients with EBV infection, EBV-positive non-PTLD transplant recipients, EBV-negative transplant recipients, and healthy children. PTLD patients exhibited profound immune dysregulation, marked by weakened cytotoxicity in NK cells, reduced B cell differentiation and activation, and an inflammatory shift in myeloid cells. EBV infection primarily targeted memory B cells and plasma cells in PTLD patients, with uninfected memory B cells showing impaired functional potential. Furthermore, CD8 T cells in PTLD were characterized by increased exhaustion and low cytotoxic activity. In addition, regulatory T cells in PTLD displayed enhanced suppressive functions. Our findings present an in-depth view of the immune landscape in PTLD, identifying key immune cell alterations associated with EBV infection and PTLD development. These insights could inform the development of targeted therapies aimed at restoring immune function and controlling EBV-driven lymphoproliferation in pediatric liver transplant recipients.
IL1B gene polymorphisms (rs1143627, rs16944) increase the risk of ANCA-associated vasculitis.
Zou Q, Liu L, Chu L … +3 more , Xue C, Zhu Y, Deng J
Hum Immunol · 2025 Jul · PMID 40253228 · Publisher ↗
Neutrophils and monocytes are involved in the pathogenesis of AAV(antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis), and secreted IL-1β is also closely related to the pathogenesis of antineutrophil cytopl...
Neutrophils and monocytes are involved in the pathogenesis of AAV(antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis), and secreted IL-1β is also closely related to the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. This study aimed to investigate the association between IL1B gene polymorphisms and AAV susceptibility in the Guangxi population.We collected peripheral blood from 271 AAV patients and 297 healthy controls for DNA extraction. Genotyping of rs1143627, rs16944, and rs2853550 was performed via multiplex polymerase chain reaction combined with high-throughput sequencing. This study revealed that the allele frequencies of rs1143627 and rs16944 varied significantly between the case groups and the healthy controls (p = 0.015, p = 0.036). There was an increased risk of homozygous mutations in the rs1143627 codominant and recessive models (p = 0.046, p = 0.025). Similarly, the risk of a homozygous rs16944 mutation was increased (p = 0.08, p = 0.03). In particular, in Han Chinese women, the risk of disease development is increased. There is strong linkage disequilibrium between rs1143627 and rs16944. Among the five haplotypes,no haplotype was associated with the occurrence of disease (p > 0.05). IL1B gene polymorphisms (rs1143627, rs16944) may increase the risk of ANCA-associated vasculitis in the Guangxi population.
First report on PARK-2 gene polymorphism and its relation to clinical pathological parameters and gene expression in Non-Hodgkin lymphoma.
Tawfeek GA, Abdelaziz RA
Hum Immunol · 2025 Jul · PMID 40240244 · Publisher ↗
AIM: we investigated for first time Parkin (PARK2) gene polymorphism as a risk factor of Non-Hodgkin lymphoma (NHL) and the relation to the clinical pathological features and gene expression. MATERIALS AND METHODS: The s...
AIM: we investigated for first time Parkin (PARK2) gene polymorphism as a risk factor of Non-Hodgkin lymphoma (NHL) and the relation to the clinical pathological features and gene expression. MATERIALS AND METHODS: The study involved 142 patients with NHL and 142 healthy control. Full histories, clinical examination, performance status, An Arbor staging, International prognostic index (IPI), patient survival and laboratory investigations such as LDH, β2microglobulin and Hepatitis C virus (HCV) RNA by qualitative real time PCR were performed for all subjects. PARK-2 gene polymorphism s (rs1801474, rs1801334) was determined by PCR-RFLP, PARK-2 mRNA was assessed by qRT-PCR. RESULTS: According to GG as reference genotype, the genotypes (except GA) and A allele were significant risk factors for NHL (OR: 1.93-6.05; p = 0.004 - p < 0.001). A-G and A-A haplotypes increased the risk of NHL by 4.03 and 2.76 fold respectively (p < 0.001). It was found that AA and GA genotypes of both SNPs associated with poor performance status (p < 0.001). AA (and not GA) rs1801474 and AA &GA rs1801334 genotypes significantly associated with higher LDH (p < 0.001 & p < 0.001) and higher β2 microglobulin (p = 0.015 & p = 0.002) respectively, AA &GA genotypes of both SNPs have positive correlation with extra nodal sites and advanced staging (p < 0.001). AA genotype of both SNPs were associated with poor response to therapy and poor survival (p = 0.021 & p < 0.001). PARK-2 gene polymorphism has negative impact on PARK-2 gene expression. CONCLUSION: it is the first study to indicate that PARK-2 rs1801474 and rs1801334 SNPs carrying significant risk factors of NHL and it is correlated to some clinical pathological parameters may be due to down regulation of PARK-2 gene expression. ABBREVIATIONS: Non-Hodgkin lymphoma (NHL); diffuse large B cell lymphoma (DLBCL); follicular lymphoma (FL); and chronic lymphocytic leukemia (CLL); Over all survival (OS), progression free survival (PFS) and cancer specific survival (CSS); International prognostic index (IPI).
Study on the common mechanisms of gastroesophageal reflux disease and interstitial lung disease.
Zhang W, Cai Q, You L … +4 more , Zhang W, Zheng X, Jiang C, Chen C
Hum Immunol · 2025 May · PMID 40209518 · Publisher ↗
OBJECTIVE: Interstitial lung disease (ILD) and gastroesophageal reflux disease (GERD) have complex interactions and can exacerbate severity of each other. This study aimed to screen shared genes between ILD and GERD and...
OBJECTIVE: Interstitial lung disease (ILD) and gastroesophageal reflux disease (GERD) have complex interactions and can exacerbate severity of each other. This study aimed to screen shared genes between ILD and GERD and explore their common mechanisms and clinical value. METHODS: We obtained microarray datasets of ILD and GERD from public databases. Shared genes were screened by differential expression analysis and Venn analysis. Hub genes were screened from shared genes using the protein-protein interaction (PPI) network analysis. The ssGSEA algorithm was utilized to estimate immune infiltration level of ILD and GERD, and correlation of hub genes with immune cell infiltration was studied. Finally, potential drugs that may act on hub genes were screened using DSigDB. RESULTS: 52 shared genes were obtained through Venn analysis. PPI network analysis identified 10 hub genes (BMP4, NT5E, PPARG, EPCAM, DPP4, KLF2, MMP1, AGR2, ADAMTS1, GATA6) that may have diagnostic performance (p < 0.05). The results of immune infiltration showed that hub genes were highly linked to multiple immune cell infiltrations (p < 0.05). In addition, we identified 5 potential drugs. Notably, thioridazine may target 5 hub genes (MMP1, AGR2, KLF2, ADAMTS1, and PPARG) simultaneously (p < 0.05) and had the potential to be a novel therapeutic drug. CONCLUSION: In summary, we have screened out the hub genes with diagnostic value in ILD and GERD, and also revealed the close relationship between the hub genes and the disease immune microenvironment, providing new research directions for the common mechanism and interaction of the two diseases.
Correlation of serum vitamin D levels with serum interleukin-23 levels in patients of ulcerative colitis.
Manoria P, Noor MT
Hum Immunol · 2025 May · PMID 40199019 · Publisher ↗
Ulcerative Colitis (UC) is a chronic inflammatory condition resulting from an abnormal immune response to gut microbiota, leading to cytokine dysregulation, including elevated interleukin-23 (IL-23) levels. Emerging evid...
Ulcerative Colitis (UC) is a chronic inflammatory condition resulting from an abnormal immune response to gut microbiota, leading to cytokine dysregulation, including elevated interleukin-23 (IL-23) levels. Emerging evidence suggests that vitamin D (VD) plays a crucial role in immune modulation. However, its correlation with IL-23 in UC is not well addressed. This study aims to elucidate the relationship between serum VD and IL-23 levels in UC patients. We included forty-four UC patients and forty-four healthy controls. VD insufficiency was more common in UC patients (n = 14) compared to controls (n = 5). Significant increases in IL-23 levels were observed from remission (46.6 ± 4.3 pg/mL) to severe stages (218.5 ± 62.41 pg/mL), while VD levels did not show a similar trend. IL-23 levels also rose significantly with disease extent, from proctitis to pancolitis. A significant negative correlation was found between VD and IL-23 levels (r = -0.3175; P = 0.035). IL-23 and pulse rate were significant predictors of UC in our cohort. Our findings highlight VD insufficiency to be prevalent in UC patients, with VD levels negatively correlating with IL-23 levels, which increase with disease severity and extent. Further, understanding the interplay between VD and IL-23 will help design therapeutic interventions to modulate immune response and disease progression.
Decoding human leukocyte antigen Beta-27; its active alleles in Ankylosing Spondylitis and computational insights of potential inhibitors: HLA-B27 in AS; its variants and inhibitors.
Altaf H, Adil M, Anajirih N … +2 more , Saeed MA, Hussain N
Hum Immunol · 2025 May · PMID 40188509 · Publisher ↗
OBJECTIVES: This study aimed to determine the diverse inborn and adventitious variables that contribute to the rise of Ankylosing Spondylitis (AS) and to elucidate the genotypic study of HLA-B*27 alleles along with sub-a...
OBJECTIVES: This study aimed to determine the diverse inborn and adventitious variables that contribute to the rise of Ankylosing Spondylitis (AS) and to elucidate the genotypic study of HLA-B*27 alleles along with sub-alleles and in-silico inhibition of their respective abnormal receptor proteins by natural compounds. METHODS: Case-control study was piloted. Allele-specific DNA-based HLA typing was performed after DNA extraction. Patient questionnaires and Molecular docking was applied to identify AS prognosis and potential HLA-B*27 inhibitors respectively. RESULTS: Results revealed a 72.72% prevalence of HLA-B*27 alleles in patients versus 9.09% in controls. Sub-alleles HLA-B*27:02, 04, and 05 were identified in 87.5% of patients but were absent in controls. The chi-square (χ2) values for HLA-B*27 alleles and sub-alleles were significant, with p-values of 0.0024 and 0.0220, respectively. The study found no significant association of AS with gender, age, marital status, or environmental factors, but a strong association with family history of back pain, elevated CRP, ESR, body inflammation, and uveitis. In silico analysis identified Rutin, curcumin, and coumaroylquinic acid as natural compounds with the highest binding affinity to HLA-B27 chains A and F, suggesting their probability to modulate the structure and function of HLA-B27 proteins. CONCLUSIONS: AS is more prevalent in individuals with family history of backache, uveitis and elevated inflammatory markers, Sub-alleles of HLA-B*27 should be used as diagnostic tools alongside alleles, as they were found only in patients, not in healthy individuals. Furthermore, Rutin, curcumin, and coumaroylquinic acid may temper the function of HLA associated with AS.
Enhanced prediction of antigen and antibody binding interface using ESM-2 and Bi-LSTM.
Li Q, Zhao Y, Chordia MD … +3 more , Xia X, Zhang B, Zheng H
Hum Immunol · 2025 May · PMID 40188508 · Publisher ↗
The binding interface between antigens and antibodies is pivotal in humoral immune responses and provides crucial effective defense against pathogens and exogenous threats. Existing predictive computational methodologies...
The binding interface between antigens and antibodies is pivotal in humoral immune responses and provides crucial effective defense against pathogens and exogenous threats. Existing predictive computational methodologies, including structure-based and sequence-based approaches, offer valuable insights but face challenges such as unknown antigen structures and reliance on manually curated features. Most current methods primarily predict antigen epitope, often neglecting the specific molecular epitope-paratope interactions essential for immune efficacy. In this study, we introduce a novel approach EPP (Epitope-Paratope Predictor), using the ESM-2 protein language model as a feature encoder and a Bi-LSTM network to predict epitope-paratope interactions. Our method processes antigen and antibody sequences as inputs, leveraging a novel dataset strategy and encoding protein representations to enhance prediction accuracy. The results demonstrate a significant improvement in prediction accuracy compared to existing methods, highlighting the importance of protein feature encoder and temporal dependencies within sequences. The model's performance in different antigen clusters is analyzed, while those predictions are compared with that from AlphaFold3 and Dock method. Our method validation shows superior performance in recognizing distinctive epitopes of the same antigen when bound to different antibodies. This approach offers a new strategy for an in-depth understanding of antigen-antibody interactions, essential for an array of pioneer projects, such as structure-guided design and affinity maturation for precision antibodies targeting a given epitope.
The number and frequency of mucosal-associated invariant T (MAIT), γδ T, and innate lymphoid cells (ILCs) altered in patients with type I Gaucher disease.
Uzen R, Bayram F, Dursun H … +5 more , Kardas F, Cakir M, Cucer N, Eken A, Donmez-Altuntas H
Hum Immunol · 2025 May · PMID 40184787 · Publisher ↗
INTRODUCTION: Gaucher disease (GD) is a rare lysosomal storage disease caused by mutations in the Glucocerebrosidase (GBA) gene. The innate immunopathology of GD beyond macrophage involvement is not well characterized. I...
INTRODUCTION: Gaucher disease (GD) is a rare lysosomal storage disease caused by mutations in the Glucocerebrosidase (GBA) gene. The innate immunopathology of GD beyond macrophage involvement is not well characterized. In the current study, the changes in ILC subsets, γδ T and MAIT cells, TNF-α and IFN-γ cytokine levels in the peripheral blood of patients with Type 1 GD and GD carriers were evaluated. METHODS: Peripheral blood mononuclear cells obtained from patients and controls were isolated using the Ficoll-Paque gradient method; after surface and intracellular staining, the cells were analyzed on FACSARIA III. RESULTS: Our analyses revealed that CD8 MAIT cells and CD8 γδ T cells are reduced in the treated patients compared with the carriers. MAIT cell-specific IFN-γ production and absolute counts of IFN-γ MAIT cells significantly decreased in Type 1 GD patients who received ERT compared with healthy controls, which could be important indicators for the pathogenesis and severity of the disease. Additionally, total ILCs, particularly the ILC1 subset, were reduced in the Type I GD patients receiving ERT compared with healthy controls and the carriers. CONCLUSION: The changes observed in ILCs, γδ T cells, MAIT cells, TNF-α and IFN-γ cytokine levels in both pre- and post-treatment Type 1 GD patients may play a vital role in the pathogenesis of GD.
The impact of donor-specific antibody and non-HLA antibodies on acute cellular rejection in pediatric liver transplantation.
Xu Q, Bedoyan SM, Bentlejewski C … +4 more , Sindhi R, Mazariegos GV, Zeevi A, Squires JE
Hum Immunol · 2025 May · PMID 40157164 · Publisher ↗
Antibodies to HLA or non-HLA antigens are associated with detrimental outcomes in organ transplants. Here, we aim to examine whether donor-specific antibodies (DSA) and non-HLA antibodies are associated with rejection in...
Antibodies to HLA or non-HLA antigens are associated with detrimental outcomes in organ transplants. Here, we aim to examine whether donor-specific antibodies (DSA) and non-HLA antibodies are associated with rejection in a single-center cohort of 101 pediatric liver transplant (PLTx) recipients. Rejection was found in 50/101 biopsies (49.5 %). DSA was positive in 32 paired sera and associated with rejection (HR = 2.63[1.10-6.30]). Antibodies to 3 non-HLA antigens, SNRPB (small nuclear ribonucleoprotein polypeptides B), GSTT1 (Glutathione S-transferase theta-1), and Actin were associated with rejection. Rejection was found in 22/35 cases positive for any of the three non-HLA antibodies. The presence of DSA and non-HLA antibodies was associated with an augmented risk of rejection (HR = 6.32[1.57-25.30], p < 0.01]. In conclusion, DSA or non-HLA antibodies were associated with a higher risk for rejection in PLTx recipients. When they were detected concomitantly, the risk for rejection increased significantly, indicating the synergistic effect of actions.
Defining a normal reference range for B cells: A key to diagnosing humoral inborn errors of immunity.
van Heerden G, Kassiem R, Hlongwa L … +1 more , Mayne E
Hum Immunol · 2025 May · PMID 40154099 · Publisher ↗
B cells are integral components of the adaptive immune response that develop in distinct stages, producing various subsets with specialized roles. Abnormal B cell subsets development is associated with humoral inborn err...
B cells are integral components of the adaptive immune response that develop in distinct stages, producing various subsets with specialized roles. Abnormal B cell subsets development is associated with humoral inborn errors of immunity (IEI) and so assessment of B cell subsets is a component of humoral IEI diagnosis and should be compared to a reference range which is age- and population-specific although relatively few studies on B-cell subsets have been published in Africa populations when compared with other populations and not all studies evaluate the same subsets or in the same age-groups. This highlights the need for local studies to establish locally relevant reference ranges.
Investigation of immune checkpoint molecules (CTLA-4, PD-1, PD-L1, Tim-3) expressions in preeclampsia: A comparative study of membranous and soluble forms.
Parhizkar F, Shekari N, HajiEsmailPoor Z … +4 more , Parsania S, Soltani-Zangbar MS, Aghebati-Maleki A, Aghebati-Maleki L
Hum Immunol · 2025 May · PMID 40154098 · Publisher ↗
Preeclampsia (PE) is characterized by immune dysfunction, including altered expression levels of multiple immune checkpoints (ICs), which are essential for inducing immune tolerance during pregnancy. While the pivotal ro...
Preeclampsia (PE) is characterized by immune dysfunction, including altered expression levels of multiple immune checkpoints (ICs), which are essential for inducing immune tolerance during pregnancy. While the pivotal role of ICs in PE is well-established, a limited understanding remains of the changes in their various forms, particularly in their membranous and secretory states. This study focused on exploring the probable role of ICs in the pathophysiology of PE via measuring the levels of their transmembrane and soluble forms. Initially, expression levels of transmembrane CTLA-4, PD-1, PD-L1, and Tim-3 on PBMCs of PE patients were assessed through qRT-PCR and western blot analysis. Additionally, ELISA was performed to evaluate their soluble forms in serum. Finally, the correlation between transmembrane and soluble forms was determined. PE patients exhibited decreased CTLA-4, PD-1, and Tim-3 expression, while PD-L1 was increased compared to the healthy group. sCTLA-4 and sPD-L1 were reduced in serum; however, sPD-1 and sTim-3 were increased. The expression of CTLA-4 on PBMCs was positively correlated with sCTLA-4. Meanwhile, PD-1, PD-L1, and Tim-3 expressions were negatively correlated with soluble forms. The observed abnormal expression levels of transmembrane CTLA-4, PD-1, PD-L1, and Tim-3 on PBMCs, along with their soluble counterparts in serum, indicate their possible role in the pathogenesis of PE. Thus, variations in these ICs' expression could enhance the differentiation of PE and aid in developing targeted therapeutic strategies.
A case-control association study of APOE promoter region variants with glaucoma in North Indian population.
Passan S, Goyal S, Bhat MA … +3 more , Singh R, Kaur M, Vanita V
Hum Immunol · 2025 May · PMID 40154097 · Publisher ↗
PURPOSE: Genetic variants in apolipoprotein E (APOE) are reported as risk factors for glaucoma in different ethnic populations, however, there is a scarcity of data from North India. Therefore, the present study aimed to...
PURPOSE: Genetic variants in apolipoprotein E (APOE) are reported as risk factors for glaucoma in different ethnic populations, however, there is a scarcity of data from North India. Therefore, the present study aimed to investigate the association of APOE promoter region variants c.-219T > G, c.-427T > C, and c.-491A > T with glaucoma in the North Indian population. METHODS: 286 primary glaucoma patients and 300 healthy controls were included in the present study. Promoter region variants (c.-219T > G, c.-427T > C, c.-491A > T) of APOE were genotyped by Sanger sequencing followed by statistical analyses. RESULTS: Present case-control association analysis indicated that the GG genotype of the c.-219T > G variant is more common in glaucoma patients (18.53 %) than in controls (11.33 %) and conferred a 1.9-fold increased risk of glaucoma (OR = 1.92, 95 % CI 1.16-3.16, p = 0.010). This risk is particularly higher in females, showing a 2.7-fold increase (OR = 2.66, 95 % CI 1.10-6.41, p = 0.028). In the recessive model, the GG genotype also exhibited a 1.8-fold increased risk of glaucoma development (OR = 1.78, 95 % CI 1.12-2.83, p = 0.014). During sub-group analysis, GG genotype was more prevalent in POAG group compared to controls, with a 2.3-fold increased risk (OR = 2.27, 95 % CI 1.32-3.89, p = 0.002). However, no significant differences in genotype distribution were found between PACG and PCG vs. controls. Additionally, the genotype and allele frequency distributions for the c.-427T > C and c.-491A > T variants were not statistically significant between cases and controls. CONCLUSION: Our study shows the association of the c.-219T > G variant in the development of glaucoma in the analyzed Indian population. The present study analyzed the genotype-phenotype correlation between APOE promoter region variants and glaucoma characteristics in the Indian population.
Novel HLA-A, -B, -C and -DRB1 alleles identified in the Australian New South Wales tissue typing laboratory.
Velickovic M, Turner TR
Hum Immunol · 2025 May · PMID 40132251 · Publisher ↗
HLA compatibility between patients and donors is a determining factor for the success of stem cell and solid organ transplantations. However, finding suitable donors remains challenging due to the highly polymorphic natu...
HLA compatibility between patients and donors is a determining factor for the success of stem cell and solid organ transplantations. However, finding suitable donors remains challenging due to the highly polymorphic nature of HLA genes. Here we are describing 16 novel HLA-A, -B, -C and -DRB1 alleles identified over the period of 2 years. Fourteen differed from their closest reference allele sequence by single nucleotide substitutions detected in the coding regions and 13 contained polymorphism outside antigen recognition domains (exons 2 and 3 in class I and exon 2 in HLA class II). Two novel alleles, a non-sense substitution and a deletion of 2 bp resulted in two null alleles, while a substitution in a splice site resulted in an allele with questionable expression status. In HLA matching procedures, particularly in donor selection, it is important to determine alternatively expressed HLA alleles. Thirteen additional HLA-A, -B, -C and -DRB1 alleles detected as novel at the time of testing were already reported by other laboratories by the time of submission.
The evolving role of B cells in malignancies.
Bindu S, Bibi R, Pradeep R … +1 more , Sarkar K
Hum Immunol · 2025 May · PMID 40132250 · Publisher ↗
B cells play diverse roles in different pathological circumstances, such as neoplastic diseases, autoimmune disorders, and neurological maladies. B cells, which are essential elements of the adaptive immune system, demon...
B cells play diverse roles in different pathological circumstances, such as neoplastic diseases, autoimmune disorders, and neurological maladies. B cells, which are essential elements of the adaptive immune system, demonstrate exceptional functional variety, including the generation of antibodies, the presentation of antigens, and the secretion of cytokines. Within the field of oncology, B cells display a multifaceted nature in the tumor microenvironment, simultaneously manifesting both tumor-promoting and tumor-suppressing characteristics. Studies have found that the existence of tertiary lymphoid structures, which consist of B cells, is linked to better survival rates in different types of cancers. This article examines the involvement of B cells in different types of malignancies, emphasizing their importance in the development of the diseases and their potential as biomarkers. Additionally, the review also examines the crucial role of B cells in autoimmune illnesses and their potential as targets for therapy. The article also analyses the role of B cells in immunization and exploring their potential uses in cancer immunotherapy. This analysis highlights the intricate and occasionally contradictory roles of B cells, underlining the necessity for additional research to clarify their varied actions in various illness scenarios.
DonorCheck: A quality control tool to validate the interpretation and data entry of HLA typing results used for organ allocation.
Muluhngwi P, Hiner MC, Clarke K … +7 more , Cole BR, Greenwood MP, Beutel KM, Kremer M, Tumer G, Maurer D, Pankratz N
Hum Immunol · 2025 May · PMID 40121738 · Publisher ↗
HLA (human leukocyte antigen) typing is performed on both organ donors and recipients to ensure compatibility and thus maximize graft and patient survival. In the US, the final assigned HLA typing is then entered, often...
HLA (human leukocyte antigen) typing is performed on both organ donors and recipients to ensure compatibility and thus maximize graft and patient survival. In the US, the final assigned HLA typing is then entered, often manually, into the DonorNet system managed by United Network for Organ Sharing (UNOS), where it is used to generate a list of potential recipients. For deceased donor organs, HLA typing is most often performed via real-time PCR (rtPCR), which is rapid and robust but requires human interpretation. Human error in that interpretation or in the data entry process (regardless of whether the typing is generated by rtPCR or sequencing) can have severe consequences including organ wastage due to inappropriate matching and graft rejection. UNOS requires laboratories to validate the accuracy of their DonorNet submission. To address this need, we have developed DonorCheck (https://github.com/PankratzLab/DonorCheck/), an open-source and user-friendly software application written in Java that validates DonorNet field entries against the original donor HLA typing source report. DonorCheck helps HLA laboratories independently validate their interpretation of rtPCR data (including accounting for allele, P-group, and serotype lookup) and the HLA data entry into DonorNet, reduce data entry errors, and enhance patient safety.
Cytomegalovirus-associated CD57 + KLRG1 + CD8 + TEMRA T cells are associated with reduced risk of CMV viremia in kidney transplantation and chronic allograft dysfunction in lung transplantation.
Pickering H, Arakawa-Hoyt J, Llamas M … +13 more , Ishiyama K, Sun Y, Parmar R, Sen S, Bunnapradist S, Hays SR, Singer JP, Schaenman JM, Lanier LL, Reed EF, Calabrese DR, Greenland JR, CMV Systems Immunobiology Group
Hum Immunol · 2025 May · PMID 40120236 · Full text
Cytomegalovirus (CMV) infection threatens outcomes across solid organ transplantation, but organ-specific differences in CMV immunity are incompletely understood. We investigated whether lung and kidney CMV infection dro...
Cytomegalovirus (CMV) infection threatens outcomes across solid organ transplantation, but organ-specific differences in CMV immunity are incompletely understood. We investigated whether lung and kidney CMV infection drove similar immune profiles, hypothesizing that CMV-associated T cells would be associated with graft function. We longitudinally examined 41 lung transplant (LTx) recipients and 31 kidney transplant (KTx) recipients with CMV viremia, alongside non-viremic controls. We performed flow cytometry and single-cell protein and transcriptomic profiling (CITE-seq) on blood cells. Chronic lung allograft dysfunction (CLAD)-free survival and glomerular filtration rate decline-free survival were assessed by Cox proportional-hazards models. Terminal effector memory (TEMRA) CD8 T cells segregated by expression of CD57 and KLRG1. CMV viremia led to expansion of CD57 TEMRA in both cohorts (P < 0.001). In KTx, increased frequency of CD57KLRG1 were associated with viremia control (P = 0.05). In LTx, frequency > median of CD57KLRG1 conferred a 67 % reduced risk for CLAD or death (95 % CI; 3-89 % P = 0.04). CD57KLRG1 TEMRA showed evidence of cytotoxic and effector function, whereas CD57KLRG1 TEMRA showed evidence of exhaustion. CD57KLRG1 TEMRA were most active against CMV and reduced risk for viremia in KTx and CLAD in LTx. This population merits increased attention for its potential role in mediating CMV-associated transplant outcomes.
Computational predictions of artificial nucleoside triphosphates as potent inhibitors of RNA-dependent RNA polymerase of the ZIKA virus.
Pant S, Jena NR
Hum Immunol · 2025 May · PMID 40117673 · Publisher ↗
As the RNA-dependent RNA polymerase (RdRp) of the Zika virus (ZIKV) is responsible for replicating the viral RNA genome inside host cells, its inhibition is necessary to control the Zika viral disease. Here, the interact...
As the RNA-dependent RNA polymerase (RdRp) of the Zika virus (ZIKV) is responsible for replicating the viral RNA genome inside host cells, its inhibition is necessary to control the Zika viral disease. Here, the interactions of 16 artificial RNA and DNA nucleoside triphosphates with the substrate active site of RdRp are studied in detail by using the molecular docking technique. The top 8 hits containing ligands such as ZTP, BTP, STP, XTP, dZTP, dBTP, dSTP, and dXTP were further studied by using molecular dynamics, and MM/GBSA Free-energy methods. It is revealed that among various nucleoside triphosphates studied herein, the dBTP would bind to RdRP most strongly with a binding free energy (ΔG) of -70.40 ± 4.6 kcal/mol followed by dZTP with a ΔG of -67.37 ± 3.1 kcal/mol. The binding of these artificial nucleoside triphosphates to RdRp is about 22-26 kcal/mol more stable than that of the natural nucleoside triphosphate GTP. Therefore, it is expected that dBTP and dZTP would inhibit the activities of RdRp strongly. The molecular mechanisms of inhibition of RdRp activities are also discussed and compared with experimental studies.
Pyrimethamine treatment in breast cancer lysate-loaded dendritic cells promotes autologous T cells' anti-tumor responses in vitro.
Sohrabi S, Masoumi J, Naseri B … +7 more , Baghbani E, Kazemi T, Maleki LA, Doustvandi MA, Ghahramanipour Z, Alipour S, Baradaran B
Hum Immunol · 2025 May · PMID 40112492 · Publisher ↗
BACKGROUND: Suppressing inhibitory molecules such as signal transducer and activator of transcription (STAT) 3 in dendritic cells (DCs) and eliciting an effective immune response via T cells against antigens (Ags) produc...
BACKGROUND: Suppressing inhibitory molecules such as signal transducer and activator of transcription (STAT) 3 in dendritic cells (DCs) and eliciting an effective immune response via T cells against antigens (Ags) produced exclusively by malignant cells represents the major method in the process of DC-based vaccines. Pyrimethamine (Pyri), a potential STAT3 inhibitor, is an antimalarial drug that is employed for ameliorating various cancers, including breast cancer. The present study aimed to investigate T cell-mediated responses after DCs and T cells co-culturing using breast cancer lysate (BCL) and Pyri to inhibit STAT3 protein in the DCs for the first time. METHOD: Employing the Magnetic Activated Cell Sorting (MACS) technique, monocytes were separated from peripheral blood mononuclear cells (PBMCs). After monocytes were differentiated into DCs, they were divided into two groups: mature dendritic cells (mDCs) (received lipopolysaccharide (LPS) and BCL) and Pyrimethamine-treated mature dendritic cells (Pyri-mDCs) (incubated with LPS, BCL, and Pyri). Flow cytometry was used to examine the surface markers related to DC phenotype in both groups of DCs. Consequently, RT-PCR was employed to investigate the expression of genes linked to inflammatory and anti-inflammatory cytokines in mDCs and Pyri-mDCs as well as related genes to T cell response after DC/T cell co-culturing. RESULTS: Our outcomes revealed that Pyri-mediated STAT3 inhibition in DCs upregulates and downregulates the expression of inflammatory and anti-inflammatory cytokines' genes. Furthermore, co-culture of Pyri-mDCs with autologous T cells downregulated T helper (Th) 2 and regulatory T cell (Treg) responses and augmented Th1 activation compared to T cell cultured along with mDCs. CONCLUSION: Overall, our research points to Pyri-mediated STAT3 suppression in DCs loaded with BCL as a potentially effective therapeutic method for inducing effective T cell responses; nevertheless, additional investigation is required to evaluate the effectiveness of this approach especially in pre-clinical settings.
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