Human Immunology[JOURNAL]
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200 papers
Intronic region polymorphisms of autophagy gene ATG16L1 predispose individuals to Hepatitis B virus infection.
Sharma A, Duseja A, Parkash J … +1 more , Changotra H
Hum Immunol · 2025 May · PMID 40112491 · Publisher ↗
Intronic region polymorphisms, rs2241879 G/A, rs13005285 G/T, and rs7587633 C/T of ATG16L1 were analyzed in this case-control study in HBV-infected patients to find their role in HBV infection. The mutant alleles rs22418...
Intronic region polymorphisms, rs2241879 G/A, rs13005285 G/T, and rs7587633 C/T of ATG16L1 were analyzed in this case-control study in HBV-infected patients to find their role in HBV infection. The mutant alleles rs2241879A (OR = 1.57) and rs13005285T (OR = 1.39) were the risk factors for HBV infection. These alleles were associated with different stages of infection: asymptomatic rs13005285T (OR = 1.91), acute rs13005285T (OR = 1.58), chronic rs2241879A (OR = 1.62), and cirrhosis rs2241879A (OR = 3.02). Moreover, on applying various genetic models, rs2241879A predisposed individuals to HBV infection (homozygous model; AA vs. GG; OR = 2.58). Patients with CHB infection, the homozygous model showed an OR of 2.79, while the dominant model had an OR of 1.96. Among cirrhosis patients, the homozygous model resulted in an OR of 9.43, and the dominant model showed an OR of 4.92. The rs13005285 variant significantly increased the risk of acute HBV infection in the co-dominant model (OR = 1.78) and dominant model (OR = 1.84). Individuals with the rs7587633 variant at the asymptomatic stage of infection showed a reduced risk under the co-dominant model (OR = 0.41) and the dominant model (OR = 0.54). We identified GCG, GTG and GCT haplotypes corresponding to rs2241879, rs7587633, and rs13005285 SNPs, which play a protective role in HBV infection. Furthermore, we also developed a PCR-ARFLP assay for genotyping rs13005285G/T which would help to analyze this polymorphism in low-income settings where high-end instrumentation is not accessible.
Anti-HLA class I donor-specific antibodies are associated with lower overall and event-free survival and late mortality in outpatient haploidentical-related stem cell transplantation from the peripheral blood.
Jaime-Pérez JC, Robles-Valverde C, Domínguez-Villanueva A … +5 more , Ruiz-De la Cruz ML, Moncada-Saucedo NK, Mendoza-Ibarra SI, Barragán-Longoria RV, Gómez-Almaguer D
Hum Immunol · 2025 May · PMID 40096769 · Publisher ↗
BACKGROUND: Donor-specific (DSA) anti-HLA antibodies can adversely influence outcomes of haploidentical hematopoietic stem cell transplantation (haplo-HSCT). METHODS: Patients who received a haplo-HSCT from a sibling aft...
BACKGROUND: Donor-specific (DSA) anti-HLA antibodies can adversely influence outcomes of haploidentical hematopoietic stem cell transplantation (haplo-HSCT). METHODS: Patients who received a haplo-HSCT from a sibling after reduced-intensity conditioning (RIC) and had a virtual cross match against donor's HLA typing performed and a positive single-antigen microsphere-based immunoassay test were studied. DSA were considered positive with a mean fluorescence intensity (MFI) ≥ 1000. RESULTS: Anti-HLA DSA ≥ 1000, median 2623(range 1000-13,235) MFI were documented in 27/65 (42 %) patients. In 14 (21.5 %) patients, antibodies were anti-HLA class I, in 18 (27.7 %) anti-HLA class II, and in 6 (9.2 %) against both. Overall (OS) and event-free survival (EFS) were lower in patients with anti-HLA Class I DSA (p = 0.026 and p = 0.037, respectively). One-year mortality was higher with anti-HLA DSA of any class (p = 0.009). Nine (64.3 %) of 14 patients with DSA anti-HLA class I died, vs. 11/18 (61 %) with class II DSA (p = 0.238). Anti-HLA DSA were not associated with graft failure (GF) in the cohort. There was no difference in relapse or acute or chronic GVHD in patients with and without DSA. CONCLUSION: Anti-HLA Class I DSA > 1000 MFI after haplo-HSCT was associated with lower OS and EFS and higher one-year mortality, but no with GF, acute or chronic GVHD, or relapse.
Immunologic and genetic differences and similarities between skin diseases.
Kuśnierczyk P, Mintoff D, Niepiekło-Miniewska W
Hum Immunol · 2025 May · PMID 40090202 · Publisher ↗
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Association of TNFAIP3 expression and gene polymorphisms with systemic lupus erythematosus susceptibility in the Chinese Han population.
Yang Q, Wei G, Zhou X … +2 more , He Y, Chen J
Hum Immunol · 2025 May · PMID 40090201 · Publisher ↗
Systemic lupus erythematosus (SLE) is an autoimmune disease with complex underlying mechanisms that have not been fully elucidated. Tumor necrosis factor-α induces protein 3 (TNFAIP3) has been identified as an SLE suscep...
Systemic lupus erythematosus (SLE) is an autoimmune disease with complex underlying mechanisms that have not been fully elucidated. Tumor necrosis factor-α induces protein 3 (TNFAIP3) has been identified as an SLE susceptibility gene. This study aimed to investigate the association between TNFAIP3 levels in peripheral blood mononuclear cells (PBMCs), TNFAIP3 single nucleotide polymorphisms (SNPs), and SLE genetic susceptibility. The mRNA expression level of the TNFAIP3 and the concentration of A20 protein were significantly reduced and negatively correlated with disease activity in patients with active SLE. The C allele of rs377482653 was positively correlated with SLE susceptibility (T vs C: OR = 1.74, 95 %CI: 1.09-2.78, p = 0.02). There were no significant differences in the allele frequencies of rs582757 (p = 0.60), rs583522 (p = 0.40) and rs10499194 (p = 0.38) between SLE and healthy controls. Individuals with the rs377482653 C allele and CT genotype were more likely to develop arthritis (C: OR = 1.94, 95 %CI: 1.03-3.63, p = 0.04; CT: OR = 2.54, 95 %CI: 1.19-5.43, p = 0.02). Thus, we established that SLE shows a lower expression of TNFAIP3 and that rs377482653 polymorphism is associated with SLE.
Associations of HLA-DRB1 shared epitope alleles with cardiovascular disease and events in a multi-ethnic community-living population: The multi-ethnic study of atherosclerosis (MESA).
Kaur M, Katz R, Criqui MH … +5 more , Corr M, Post WS, Budoff M, Morris GP, Hughes-Austin JM
Hum Immunol · 2025 May · PMID 40068347 · Full text
OBJECTIVE: Rheumatoid arthritis (RA) has been considered an independent risk factor for cardiovascular disease (CVD), where RA and CVD later manifest following genetic predisposition and an extended preclinical phase.The...
OBJECTIVE: Rheumatoid arthritis (RA) has been considered an independent risk factor for cardiovascular disease (CVD), where RA and CVD later manifest following genetic predisposition and an extended preclinical phase.TheHLA-DRB1Shared Epitope (SE)allelespredispose for RA andare associated withhigherrisk of CV mortality in RA patients, but have not been evaluated in a community-living population.Thus, we evaluated whetherHLA-DRB1 (SE) alleleswereassociated with subclinical CVD, CV events, and mortality in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: We performed HLA typing in 955 MESA participants and evaluated associations of SE alleles with coronary artery calcium (CAC) and abdominal aortic calcium (AAC); risk difference for CAC, AAC severity, and carotid intima media thickness (cIMT); and associations of SE with all-cause mortality, CVD and non-CVD death, and CV events. RESULTS: Among 955 participants, 30 % were HLA-DRB1 SE positive. SE positivity was not significantly associated with higher risk of CAC, AAC, cIMT, CV events, or mortality. DRB1*10:01 demonstrated 2.63-fold higher risk for CAC (95 % CI 1.17-5.99); DRB1*14:02 demonstrated 42 % higher risk for AAC (95 % CI 1.17-1.74); and DRB1*04:05 demonstrated 24 % lower risk for AAC (95 % CI 0.58-0.99). CONCLUSION: In a multi-ethnic community-living population, HLA-DRB1 SE alleles were not associated with subclinical CVD, CV events, or mortality. However, individual allele-associations with subclinical CVD suggested variability in risk.
Genetic variants in the IFNGR2 locus associated with severe chronic Q fever.
David S, Castro L, Duarte E … +10 more , Gaspar U, da Costa Rodrigues MR, Cueto-Rojo MV, Mendonça J, Ferrão J, Machado M, Poças J, Lavinha J, Vieira L, Santos AS
Hum Immunol · 2025 May · PMID 40056764 · Publisher ↗
Q fever is a highly contagious zoonosis capable of causing large outbreaks of important health and economic consequences. Host genetic factors are believed to influence the development of severe chronic Q fever following...
Q fever is a highly contagious zoonosis capable of causing large outbreaks of important health and economic consequences. Host genetic factors are believed to influence the development of severe chronic Q fever following the infection by the etiological agent, Coxiella burnetii. Targetted next generation sequencing (NGS) was performed in a case-control genetic association study on 53 confirmed Q fever cases, including 38 compatible with acute and 15 with chronic disease, and 29 samples from the general Portuguese population. Four SNPs in the IFNGR2 locus, rs78407108 G > A, rs17879956 C > T, rs7277167 C > T, and rs9974603 C > A, showed a statistically significant association to chronic Q fever, resisting the Bonferroni correction. These belonged to haplotypes significantly associated with chronic Q fever. The individual SNPs are referenced in the GTEx database as possible eQTLs. Given the direct bearing of IFNGR2 on IFN-γ signaling, the possible involvement of the associated variants with higher IFNGR2 expression could be in line with observations suggesting that IFN-γ production in chronic Q fever patients is significantly higher than in healthy controls. Further investigations are required to clarify the role of IFNGR2 signaling in association with chronic Q fever.
JoGo-LILR caller: Unveiling and navigating the complex diversity of LILRB3-LILRA6 copy number haplotype structures with whole-genome sequencing.
Nagasaki M, Hirayasu K, Khor SS … +4 more , Otokozawa R, Sekiya Y, Kawai Y, Tokunaga K
Hum Immunol · 2025 May · PMID 40054016 · Publisher ↗
Leukocyte immunoglobulin-like receptors (LILRs), encoded on human chromosome 19q13.4, comprise a set of 11 immunoglobulin superfamily receptors known for their genetic heterogeneity. Notably, LILRB3 and LILRA6 within thi...
Leukocyte immunoglobulin-like receptors (LILRs), encoded on human chromosome 19q13.4, comprise a set of 11 immunoglobulin superfamily receptors known for their genetic heterogeneity. Notably, LILRB3 and LILRA6 within this cluster exhibit pronounced sequence homology in immunoglobulin-like domains involved in ligand binding and variable copy number (CN) states. However, understanding their precise role remains challenging. To address this difficulty, we developed an algorithm and tool named JoGo-LILR Caller, which jointly calls CNs of LILRB3 and LILRA6 from a population-scale whole-genome short-read sequencing dataset. This tool was applied to 2,504 international HapMap samples and yielded a global CN profile. The 100 % concordance rate corroborated this profile with the CN data obtained from 40 samples of pangenome reference assemblies provided by the Human Pangenome Reference Consortium (HPRC). The frequencies of LILRB3-LILRA6 CN haplotype structures were also estimated for five continental groups with a global CN profile. The established allele frequency profile allowed our tool to estimate LILRB3-LILRA6 CN haplotype combinations. JoGo-LILR-trio enhanced the prediction reliability for haplotype pairs within trio datasets, with trio analysis on 40 child samples demonstrating a 100 % concordance between the predicted pair of haploid CN types and the diploid reference assemblies. Its utility will extend to facilitating software advancements for imputing LILRB3-LILRA6 CN types from SNP array genotyping data, enabling subsequent association analyses that link these CN types to diverse phenotypic traits and diseases, e.g., inflammatory bowel diseases and Takayasu arteritis.
Combined next generation sequencing for HLA typing and chimerism testing.
Tyler J, Casey H, Mowery C … +2 more , Kessler N, Shike H
Hum Immunol · 2025 May · PMID 40043508 · Publisher ↗
Two NGS-based assays, HLA typing (HLA-A, B, C, DRB1/3/4/5, DQA1/B1, DPA1/B1) and chimerism testing (202 single nucleotide polymorphisms) were combined and sequenced together, using the MiSeq V2 reagent kit. The HLA typin...
Two NGS-based assays, HLA typing (HLA-A, B, C, DRB1/3/4/5, DQA1/B1, DPA1/B1) and chimerism testing (202 single nucleotide polymorphisms) were combined and sequenced together, using the MiSeq V2 reagent kit. The HLA typing library pool (sample number: X, 1.42 nM) and the chimerism library pool (sample number: Y, 1.33 nM) were combined at the volume ratio X:2Y (X + 2Y ≤ 100). Chimerism MiSeq sample sheets (dual index) were edited to support 150 bp read length and uploaded to the BaseSpace Sequence Hub. After NGS, chimerism FASTQ files were downloaded and analyzed. An HLA typing MiSeq sample sheet was then uploaded to requeue indices for FASTQ file generation. Both the combined and the separate NGS achieved sufficient read numbers, sequence quality, chimerism assay sensitivity of 0.1 %, and comparable test results on clinical samples (HLA typing, N = 44; chimerism genotyping, N = 24, % recipient chimerism, N = 95). Potential benefits and considerations in combining NGS-based tests are discussed.
Immune dysregulation in glycogen storage disease 1b extends beyond neutropenia.
Gehlhaar A, Shouval DS, Santiago EG … +5 more , Ling G, McCourt B, Werner L, Yerushalmi B, Konnikova L
Hum Immunol · 2025 May · PMID 40037121 · Publisher ↗
Glycogen Storage Disease type 1b (GSD1b) is a rare disease manifesting as hypoglycemia, recurrent infections and neutropenia, resulting from deleterious mutations in the SLC37A4 gene encoding the glucose-6-phosphate tran...
Glycogen Storage Disease type 1b (GSD1b) is a rare disease manifesting as hypoglycemia, recurrent infections and neutropenia, resulting from deleterious mutations in the SLC37A4 gene encoding the glucose-6-phosphate transporter. Classic treatment strategies in GSD1b focus on restoring neutrophil numbers and function; however, the immune defect is believed to be multifactorial and extensive immunophenotyping characterization is currently missing. Here we apply a systems immunology approach utilizing Cytometry by Time of Flight (CyTOF) to map the peripheral immune landscape of 6 GSD1b patients. When compared to control subjects, those with GSD1b had a significant reduction in immune sub-populations of classical monocytes, non-classical monocytes, and natural killer cells. Additionally, there was a preference towards a central versus an effector memory phenotype in multiple T cell populations. We also identified a global reduction of CD123, CD14, CCR4, CD24 and CD11b across several populations and a multi-cluster with upregulation of CXCR3, hinting at a potential role of impaired immune cell trafficking in the context of GSD1b. Taken together, our data suggest that that the immune impairment observed in GSD1b patients extends beyond neutropenia and affects innate and adaptive compartments, which may provide novel insights into the pathogenesis of this disorder.
DUSP9-mediated inhibition of IRS1/PI3K/AKT pathway contributes to insulin resistance and metabolic dysfunction in gestational diabetes mellitus.
Zhang X, Jin Y
Hum Immunol · 2025 May · PMID 40020430 · Publisher ↗
BACKGROUND: Gestational diabetes mellitus (GDM) is a common pregnancy complication associated with adverse maternal and fetal outcomes. Recent studies suggest a role for dual-specificity phosphatase 9 (DUSP9) in insulin...
BACKGROUND: Gestational diabetes mellitus (GDM) is a common pregnancy complication associated with adverse maternal and fetal outcomes. Recent studies suggest a role for dual-specificity phosphatase 9 (DUSP9) in insulin resistance and metabolic dysregulation, though its specific contribution to GDM remains unclear. This study aims to investigate the function of DUSP9 in GDM pathophysiology and its underlying molecular mechanisms. METHODS: We analyzed DUSP9 expression in umbilical cord blood and placental tissues from GDM patients (n = 16) and healthy controls (n = 14) using RT-qPCR and western blot assays. In vitro, functional assays were conducted on high glucose-induced HTR-8/SVneo trophoblast cells to evaluate the effects of DUSP9 knockdown on cell viability, apoptosis, and insulin signaling. In vivo, a GDM mouse model was constructed, and lentivirus-mediated shRNA was used to downregulate DUSP9 expression. Furthermore, metabolic parameters, including insulin resistance indices, lipid metabolism, and placental apoptosis were assessed, along with the phosphorylation status of key proteins in the IRS1/PI3K/AKT pathway. RESULTS: We first observed that DUSP9 expression was significantly upregulated in the umbilical cord blood and placental tissues of GDM patients compared to healthy controls (p < 0.01). Using high glucose-induced HTR-8/SVneo trophoblast cells to mimic GDM conditions, we found that downregulation of DUSP9 increased cell viability and inhibited apoptosis (p < 0.01). Mechanistically, co-immunoprecipitation and pull-down assays demonstrated that DUSP9 directly interacts with insulin receptor substrate 1 (IRS1) and inhibits HG-mediated IRS1 phosphorylation at Tyr632, impairing downstream insulin signaling (p < 0.01). In vivo, a GDM mouse model revealed elevated DUSP9 expression, along with significant metabolic dysfunction, including insulin resistance and increased placental apoptosis (p < 0.01). Lentivirus-mediated knockdown of DUSP9 in these mice ameliorated insulin resistance, improved lipid metabolism, and reduced placental apoptosis by improving fasting glucose and insulin levels, lipid profiles, and decreased apoptotic markers (p < 0.01). Moreover, DUSP9 knockdown in these mice promoted activation of the IRS1/PI3K/AKT signaling pathway (p < 0.01). CONCLUSIONS: DUSP9 contributes to GDM progression by inhibiting the IRS1/PI3K/AKT pathway, leading to insulin resistance and metabolic dysfunction. The knockdown of DUSP9 ameliorates key pathological features of GDM, including insulin resistance, impaired lipid metabolism, and placental apoptosis, suggesting that targeting DUSP9 may represent a potential therapeutic strategy for GDM.
HOXA9 and HOXA13 along with their shared gene targets act as common immune biomarkers in recurrent implantation failure and pre-eclampsia.
Hazra S, Chattopadhyay S, Kalapahar S … +4 more , Halder S, Chakraborty P, Chaudhury K, Goswami R
Hum Immunol · 2025 May · PMID 40020429 · Publisher ↗
Malfunctions of the complex interactions between embryo and components of decidua lead to recurrent implantation failure (RIF) and pre-eclampsia (PE). Developmental process regulatory HOX proteins (HOXA4,7,10,11) have be...
Malfunctions of the complex interactions between embryo and components of decidua lead to recurrent implantation failure (RIF) and pre-eclampsia (PE). Developmental process regulatory HOX proteins (HOXA4,7,10,11) have been extensively studied to chalk reproductive immunology-related diseases with lesser-known effects of HOXA9, HOXA13, and their targets therein. Hence, functional enrichment and differential expression analysis of HOXA9 and HOXA13 targets were conducted to identify immunological markers in RIF and PE. 517 common transcription factors (CTFs) of HOXA9 and A13 were retrieved and subjected to an in-depth bioinformatic analysis to determine different associated diseases. This was followed by pathway enrichment and protein-protein interaction analysis by DAVID and Cytoscape, respectively along with depicting structural characteristics and interaction dynamics. Overlapping CTFs in RIF and PE were identified from microarray datasets (GSE103465, GSE26787 for RIF and GSE43942, GSE10588 for PE) from GEO database to determine differentially expressed genes. Validation by qRT-PCR on eutopic endometrial samples (n = 5) obtained during window of implantation and placental tissues (n = 5) revealed significant upregulation of HOXA9 and HOXA13 with dysregulated expression of CTFs (PARVA, TFAP2A, and PHTF2) in RIF and PE. Our findings revealed common potential immune characteristics of RIF and PE which may enrich the study of related pathogenic mechanisms.
Glucose metabolism is controlled by non-coding RNAs in autoimmune diseases; a glimpse into immune system dysregulation.
Saleh RO, Aboqader Al-Aouadi RF, Almuzaini NA … +7 more , Uthirapathy S, Sanghvi G, Soothwal P, Arya R, Bareja L, Mohamed Abdelgawwad El-Sehrawy AA, Hulail HM
Hum Immunol · 2025 May · PMID 39999745 · Publisher ↗
The immune system accidentally targets the body's tissues, causing inflammation and tissue damage, the root causes of autoimmune illnesses. In recent studies, non-coding RNAs have been shown to significantly control gene...
The immune system accidentally targets the body's tissues, causing inflammation and tissue damage, the root causes of autoimmune illnesses. In recent studies, non-coding RNAs have been shown to significantly control gene expression and metabolic pathways linked to autoimmune diseases. This review investigates the effects of non-coding RNA on glucose metabolism, a route frequently dysregulated in autoimmune illnesses such as multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and diabetes. We review how non-coding RNA affects immune cell activity modulation, glucose absorption, glycolysis, and other metabolic processes critical to immune function. We also investigate the possibility of using non-coding RNA-mediated metabolic pathway targeting as a new therapeutic approach to treat autoimmune disorders. By clarifying the complex interplay of non-coding RNA, glucose metabolism, and immune dysregulation, this study endeavors to enhance comprehension of autoimmune etiology and facilitate the creation of focused therapies.
Comprehensive profiling of the heterogeneity of molecular endotypic traits in chronic rhinosinusitis.
Takahashi H, Matsuyama T, Kawabata-Iwakawa R … +2 more , Kawamoto T, Chikamatsu K
Hum Immunol · 2025 May · PMID 39986126 · Publisher ↗
Chronic rhinosinusitis (CRS) is a common clinical disease with molecular endotypes. In the present study, we performed a comprehensive transcriptomic profiling to investigate the heterogeneity of endotypes in CRS with na...
Chronic rhinosinusitis (CRS) is a common clinical disease with molecular endotypes. In the present study, we performed a comprehensive transcriptomic profiling to investigate the heterogeneity of endotypes in CRS with nasal polyps (CRSwNP). The GSE23552 dataset, which includes microarray, was acquired from the Gene Expression Omnibus database. Additionally, surgical specimens were collected at Gunma University Hospital, and reverse transcription-quantitative PCR was performed. We performed gene expression analysis, Gene Set Enrichment Analysis (GSEA), deconvolution analysis, and hierarchical clustering of samples. Gene expression analysis and GSEA revealed that type 1, type 2, and Treg-related responses, were upregulated in nasal polyp tissues when compared with those in controls. Deconvolution analysis indicated the enrichment of type 1-related cells and generation of memory T cells. Furthermore, nasal polyps exhibited higher expression of effector function- and immune checkpoint-related genes than controls. In addition, hierarchical clustering revealed the heterogeneity in patients with type 2-inflamed CRSwNP. Notably, type 1 and type 2 scores correlated with the duration from surgery to biopharmaceuticals initiation. In conclusion, our study demonstrated the heterogeneity of molecular endotypes in CRSwNP. Further characterisation and stratification are required to develop a new endotype-based precision medicine for patients with CRS.
Alterations in gut microbiota in Rheumatoid arthritis patients with interstitial lung Disease: A Comparative study.
Zhong X, Wang X, Xu L … +7 more , Zhang J, Yu W, Ji L, Huang J, Zhong X, Zhang J, Long L
Hum Immunol · 2025 Mar · PMID 39983663 · Publisher ↗
BACKGROUND: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is considered one of the most severe complications of rheumatoid arthritis. The etiology of RA-ILD is complex, involving genetic and environm...
BACKGROUND: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is considered one of the most severe complications of rheumatoid arthritis. The etiology of RA-ILD is complex, involving genetic and environmental factors. Recent studies suggest that the gut microbiota, a critical component of the immune system, may influence the pathogenesis of RA and other autoimmune disorders. However, specific data on the gut microbiota in patients with RA-ILD remain limited. OBJECTIVE: This study aimed to investigate alterations in the gut microbiota of RA-ILD patients and compare these profiles with those of RA patients without ILD and health controls. METHODS: We included three groups: RA-ILD patients (n = 30), RA patients without ILD (n = 31), and health controls (n = 30). Fresh fecal samples were collected and subjected to 16S rRNA gene sequencing to analyze microbial diversity. Statistical analyses involved α-diversity and β-diversity assessments, principal coordinates analysis (PCoA), and differential abundance testing with LEfSe and PICRUSt2. RESULTS: Significant differences in gut microbiota composition were observed between RA-ILD patients and the other groups. Notably, g_Prevotella showed differential abundance, particularly in RA-ILD patients. KEGG pathway analysis revealed upregulation in several metabolic pathways in RA-ILD compared to RA and health controls, suggesting a distinct microbial metabolic activity associated with RA-ILD. CONCLUSION: Our findings indicate that RA-ILD patients have a markedly different gut microbiota profile compared to RA patients without ILD and health controls. The observed microbial alterations may contribute to RA-ILD pathogenesis and could serve as potential biomarkers or therapeutic targets. Further studies are needed to explore these findings' clinical implications and validate the role of gut microbiota in RA-ILD progression.
Decoding immune tolerance in infertility: Exploring immune pathways and non-coding RNAs as pioneering biomarkers and therapeutic targets.
Pallathadka H, Khaleel AQ, Hjazi A … +7 more , Kumar A, Aloraibi F, Kadhum WR, Pramanik A, Hamzah HF, Mohammed SK, Mustafa YF
Hum Immunol · 2025 May · PMID 39978249 · Publisher ↗
Infertility, impacting a significant number of couples, is characterized by the failure to conceive after one year of consistent, unprotected sexual intercourse. It is multifactorial, with etiological contributors includ...
Infertility, impacting a significant number of couples, is characterized by the failure to conceive after one year of consistent, unprotected sexual intercourse. It is multifactorial, with etiological contributors including ovulatory dysfunction, male reproductive anomalies, and tubal patency issues. Approximately 15% of infertility cases are classified as "unexplained," highlighting the complexity of this condition. Lifestyle determinants such as obesity and smoking further complicate reproductive outcomes, while infertility can also indicate underlying chronic health conditions. A specialized category, immune infertility, arises from a breakdown of immunological tolerance, an essential aspect for conception and the maintenance of pregnancy. The role of various immunological components, including immune cells, cytokines, chemokines, factors like HLA-G, etc., is pivotal in this context. Moreover, non-coding RNAs (ncRNAs) have emerged as critical regulators of immune tolerance within the reproductive axis. This review synthesizes the complex immunological pathways vital for successful implantation and the early stages of pregnancy alongside the regulatory roles of ncRNAs in these processes. Offering an integrated view of molecular and immunological interactions associated with infertility seeks to enhance our understanding of potential strategies to facilitate successful conception and sustain early pregnancy.
Influence of Cytokine-Related genetic variants in TNF, IL6, IL1β, and IFNγ genes in the thalidomide treatment for Erythema nodosum leprosum in a Brazilian population sample.
Maciel-Fiuza MF, Sbruzzi RC, Feira MF … +9 more , Costa PDSS, Bonamigo RR, Vettorato R, Eidt LM, de Moraes PC, Oliveira Fam BS, Castro SMJ, Silveira MIDS, Vianna FSL
Hum Immunol · 2025 Mar · PMID 39956090 · Publisher ↗
Erythema nodosum leprosum (ENL), an inflammatory reaction in leprosy, causes painful nodules, fever, and malaise due to immune system activation. Thalidomide is an effective treatment, although associated with important...
Erythema nodosum leprosum (ENL), an inflammatory reaction in leprosy, causes painful nodules, fever, and malaise due to immune system activation. Thalidomide is an effective treatment, although associated with important adverse effects. We aimed to evaluate the association of genetic variants in genes encoding tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) with the response to treatment of ENL with thalidomide. 148 patients from the South and Northeast regions of Brazil were included. Genomic DNA was isolated from blood and/or saliva samples using commercial kits, and genetic variants in TNF, IL6, IL1β, and IFNγ genes were genotyped by TaqMan system. We identified an association between polymorphisms in TNF (rs1799964C, rs1800630A, rs1799724T and rs1800629A) IL1β (rs4848306G, rs1143623G, rs16944A, and rs1143627A), IL6 (rs2069840C and rs2069845G) and IFNγ (rs2430561T) with thalidomide dose variation in a time-dependent manner. Associations of IL6 and TNF haplotypes with thalidomide dosage variation over the time of treatment were also observed. Polymorphisms in TNF, IL6, IL1β, and IFNγ genes may modulate their expression levels, potentially impacting the required dosage of thalidomide in the treatment of ENL. Our findings should be confirmed in further studies to estimate the size effect of these polymorphisms on ENL treatment with thalidomide.
The effect of vitamin D supplementation and vaginal probiotics on fertility in women with recurrent implantation failure: A randomized clinical trial.
Badihi E, Sharifi P, Moradi A … +13 more , Kamrani A, Hassanzadeh A, Soltani-Zangbar MS, Parsania S, Afandideh F, Ahmadian Heris J, Danaii S, Shahriar B, Sadough M, Chakari-Khiavi F, Teymouri Nobari S, Aghebati-Maleki L, Yousefi M
Hum Immunol · 2025 May · PMID 39955996 · Publisher ↗
Recurrent implantation failure (RIF) is a significant obstacle in assisted reproductive technology, affecting approximately 10 % of couples undergoing in vitro fertilization (IVF). Emerging evidence suggests that vaginal...
Recurrent implantation failure (RIF) is a significant obstacle in assisted reproductive technology, affecting approximately 10 % of couples undergoing in vitro fertilization (IVF). Emerging evidence suggests that vaginal probiotics and vitamin D supplementation may improve reproductive outcomes. This randomized clinical trial evaluated the effects of these interventions on fertility in women with RIF and thin endometrium (<6 mm). A total of 112 women with a history of RIF were randomized into four groups: vaginal probiotics, vitamin D supplementation, a combination of both, or standard IVF treatment (control). The primary outcome was the pregnancy rate, confirmed by β-hCG testing and ultrasound. Secondary outcomes included changes in Th1/Th2 ratio, natural killer (NK) cell activity, and cytokine profiles. The combination group demonstrated the highest pregnancy rate (46.4 %), which was significantly higher compared with the probiotics ((14.2 %), p = 0.008), vitamin D ((17.8 %), p = 0.002), and control groups ((10.7 %), p = 0.003). Only the combination therapy significantly reduced the Th1/Th2 ratio (p < 0.001) and NK cell activity (p < 0.001), while significantly increasing IL-4 and TGF-β and decreasing IFN-γ levels (all p < 0.001). These findings suggest that combined vaginal probiotics and vitamin D supplementation may improve pregnancy outcomes by modulating the immune responses in women with RIF. This dual intervention may represent a promising strategy for enhancing fertility in this population of RIF patients.
Correlation between peripheral blood iNKT cell levels and exhaled NO in patients with allergic rhinitis.
Ge C, Zhuang H, Yu H … +1 more , Zhang C
Hum Immunol · 2025 Mar · PMID 39954629 · Publisher ↗
OBJECTIVES: This study aimed to investigate the relationship between the frequency of CD3 + TCRVα24 + iNKT cells, the proportions of iNKT CD4+, iNKT CD8 + and iNKT CD4-CD8- (DN) subgroups in peripheral blood, and nasal e...
OBJECTIVES: This study aimed to investigate the relationship between the frequency of CD3 + TCRVα24 + iNKT cells, the proportions of iNKT CD4+, iNKT CD8 + and iNKT CD4-CD8- (DN) subgroups in peripheral blood, and nasal exhaled nitric oxide (NO) levels in patients with allergic rhinitis (AR). METHODS: Peripheral blood samples were collected from 40 AR patients and 40 patients with nasal septal deviation (DNS). The frequencies of the iNKT cell subgroups were analyzed, and nasal exhaled NO levels were measured. Correlation analyses were conducted to assess the associations between these parameters.. RESULTS: The frequency of CD3 + TCRVα24 + iNKT cells was significantly higher in the AR group (0.4863 % ± 0.0874 %) compared to the DNS group (0.4451 % ± 0.0603 %) (p < 0.05). The proportions of iNKT CD4+, iNKT CD8+, and iNKT CD4-CD8- (DN) cells in the AR group were 76.32 % ± 10.24 %, 12.71 % ± 4.34 %, and 11.08 % ± 6.29 %, respectively, while in the DNS group, they were 60.79 % ± 9.04 %, 13.81 % ± 5.56 %, and 25.56 % ± 6.45 %. Significant differences were observed in the proportions of iNKT CD4+ and iNKT CD4-CD8- (DN) cells between the two groups (p < 0.01). Nasal exhaled NO levels were significantly elevated in the AR group (842.33 ± 237.88 ppb) compared to the DNS group (527.37 ± 163.57 ppb, p < 0.01). In the AR group, nasal exhaled NO levels showed a strong positive correlation with the frequency of iNKT cells (r = 0.9, p < 0.01), the iNKT CD4+ subgroup (r = 0.93, p < 0.01), and a negative correlation with the iNKT CD4-CD8- (DN) subgroup (r = -0.877, p < 0.01). These findings suggest that elevated iNKT cells, particularly the iNKT CD4+ subgroup resembling T helper 2 (Th2) cells, may contribute to AR pathogenesis. CONCLUSIONS: The significant correlations between iNKT cell subgroups and nasal exhaled NO levels highlight the role of iNKT cell variations in NO-mediated AR pathogenesis. These findings also suggest the potential diagnostic value of analyzing iNKT cell profiles in AR patients.
The imbalance of follicular helper T cells and follicular regulatory T cells is involved in renal injury in active lupus nephritis.
Jiang Y, Li X, Zhou W … +7 more , Zhu H, Lao Y, Huang X, Huang L, Deng Z, Tang Y, Wang J
Hum Immunol · 2025 May · PMID 39954558 · Publisher ↗
OBJECTIVE: This study is to research the role of follicular helper T (TFH) cells and follicular regulatory T (TFR) cells in the progression of lupus nephritis (LN). METHODS: A total of 33 active LN patients, 30 stable LN...
OBJECTIVE: This study is to research the role of follicular helper T (TFH) cells and follicular regulatory T (TFR) cells in the progression of lupus nephritis (LN). METHODS: A total of 33 active LN patients, 30 stable LN patients, and 30 healthy controls (HC) were included in this study. The frequencies of TFH, TFR, T cell Ig and ITIM domain (TIGIT) + TFR, and CD226 + TFR cells in peripheral blood were measured using flow cytometry. The distribution and proportion of TFH and TFR cells in renal tissue were assessed using a multiplex immunohistochemical. RESULTS: Active LN had a significantly lower TFR and TFR/TFH ratio in peripheral blood than HC and stable LN. TIGIT + TFR was lower in active LN, while CD226 + TFR was higher. In LN, TFR and TFR/TFH ratio showed a negative correlation with creatinine (CREA), but a positive correlation with endogenous creatinine clearance (Ccr). TFH and TFR mainly infiltrated the renal interstitium or surrounding renal tubules and participated in the formation of ectopic lymphoid-like structures in active LN. In active LN, TFH cells in renal tissue were higher than in control renal tissue. The tissue TFH showed a positive correlation with the activity index, CREA, but a negative correlation with Ccr. The tissue TFR/TFH ratio showed a negative correlation with the activity index, CREA, but a positive correlation with Ccr. CONCLUSION: In active LN, the proportions of TFR cells in peripheral blood are reduced and function is impaired. In active LN, TFH and TFR imbalances have been observed and are associated with renal injury.
Exhaustion profile on classical monocytes after LPS stimulation on Crohn's disease patients.
Oliveira LPG, Xavier RG, Nora CCV … +7 more , Mangueira CLP, Rosseto EA, Aloia T, Gil JZ, Neto AS, Lopes FBTP, Carvalho KI
Hum Immunol · 2025 Mar · PMID 39952081 · Publisher ↗
Crohn's disease is a type of inflammatory bowel disease that leads to symptoms such as diarrhea, abdominal pain, weight loss, and increased risk of developing tumors. The immune system plays a vital role in the gastroint...
Crohn's disease is a type of inflammatory bowel disease that leads to symptoms such as diarrhea, abdominal pain, weight loss, and increased risk of developing tumors. The immune system plays a vital role in the gastrointestinal tract by maintaining tolerance to commensal antigens and food. However, in Crohn's disease, this tolerance mechanism is disrupted, resulting in chronic inflammatory responses. The involvement of the immune system is central to Crohn's disease, with a wide range of immune cells including monocytes, being affected. Due to the limited understanding of the role of monocytes in Crohn's disease, our study aimed to clarify the cytokine production and activation profile of monocytes subsets in the context of this condition. We used multiparametric flow cytometry to analyze the status of monocyte, quantified gene expression using qPCR, and created a correlation matrix to connect the flow cytometry data with the qPCR results through a bioinformatics approach. Our findings indicate that patients with Crohn's disease show a reduction in all monocyte subsets. Additionally, classical monocytes exhibit an exhaustion profile characterized by increased CD38 expression and reduced IL-1β production following LPS stimulation in patient groups. These results suggest that monocyte subsets play distinct roles in the disease's pathophysiology of Crohn's disease, potentially contributing to chronic inflammation and impairing the resolution of the immune response.
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