ImmunogeneticsPub Date : 2023-10-01Epub Date: 2023-07-05DOI: 10.1007/s00251-023-01307-7
Jian Xiong, Jie Yang, Yuling Sun, Yachun Chen, Yundi Guo, Cuiping Liu, Jing Sun
{"title":"Dysregulated PD-L2 is correlated with disease activity and inflammation in rheumatoid arthritis.","authors":"Jian Xiong, Jie Yang, Yuling Sun, Yachun Chen, Yundi Guo, Cuiping Liu, Jing Sun","doi":"10.1007/s00251-023-01307-7","DOIUrl":"10.1007/s00251-023-01307-7","url":null,"abstract":"<p><p>The programmed death-1 (PD-1) pathway has been shown to deliver an inhibitory signal, and aberrant expression of the PD-1 molecule and/or its ligand programmed death ligand 1 (PD-L1) has been demonstrated in human diseases, while its other ligand, programmed death ligand 2 (PD-L2), has rarely been studied. Here, we investigated the expression of PD-L2 in synovial tissue and blood from patients with rheumatoid arthritis (RA). Soluble PD-L2 and inflammatory cytokine levels in serum among healthy controls and patients with RA were compared via enzyme-linked immunosorbent assay (ELISA). Membrane PD-L2 on monocytes in blood was analyzed through flow cytometry (FCM). The different expression levels of PD-L2 between the RA and non-RA synovium were semi-quantified by immunohistochemical (IHC) staining. The soluble PD-L2 levels in serum from patients with RA were significantly lower than those in healthy subjects, correlating with active parameters (rheumatoid factor) and inflammatory cytokine secretion. The FCM results showed that patients with RA had significantly increased percentages of PD-L2-expressing CD14<sup>+</sup> monocytes and correlated with inflammatory cytokines. PD-L2 expression on macrophages in the synovium from patients with RA was recorded by IHC staining with a higher score, and its correlation with pathological scores and clinical features was determined. Together, our results revealed aberrant expression of PD-L2 in RA, which may be a promising biomarker and therapeutic target associated with the pathogenesis of RA.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":" ","pages":"425-431"},"PeriodicalIF":3.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10110767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunogeneticsPub Date : 2023-10-01DOI: 10.1007/s00251-023-01317-5
Ronald Bontrop, Martin Flajnik, Colm S O'Huigin, Masanori Kasahara
{"title":"Prof. Dr. Jan Klein (1936-2023).","authors":"Ronald Bontrop, Martin Flajnik, Colm S O'Huigin, Masanori Kasahara","doi":"10.1007/s00251-023-01317-5","DOIUrl":"10.1007/s00251-023-01317-5","url":null,"abstract":"","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":" ","pages":"413-415"},"PeriodicalIF":3.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9908837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunogeneticsPub Date : 2023-10-01Epub Date: 2023-08-09DOI: 10.1007/s00251-023-01315-7
Kara B Carlson, Cameron Nguyen, Dustin J Wcisel, Jeffrey A Yoder, Alex Dornburg
{"title":"Ancient fish lineages illuminate toll-like receptor diversification in early vertebrate evolution.","authors":"Kara B Carlson, Cameron Nguyen, Dustin J Wcisel, Jeffrey A Yoder, Alex Dornburg","doi":"10.1007/s00251-023-01315-7","DOIUrl":"10.1007/s00251-023-01315-7","url":null,"abstract":"<p><p>Since its initial discovery over 50 years ago, understanding the evolution of the vertebrate RAG- mediated adaptive immune response has been a major area of research focus for comparative geneticists. However, how the evolutionary novelty of an adaptive immune response impacted the diversity of receptors associated with the innate immune response has received considerably less attention until recently. Here, we investigate the diversification of vertebrate toll-like receptors (TLRs), one of the most ancient and well conserved innate immune receptor families found across the Tree of Life, integrating genomic data that represent all major vertebrate lineages with new transcriptomic data from Polypteriformes, the earliest diverging ray-finned fish lineage. Our analyses reveal TLR sequences that reflect the 6 major TLR subfamilies, TLR1, TLR3, TLR4, TLR5, TLR7, and TLR11, and also currently unnamed, yet phylogenetically distinct TLR clades. We additionally recover evidence for a pulse of gene gain coincident with the rise of the RAG-mediated adaptive immune response in jawed vertebrates, followed by a period of rapid gene loss during the Cretaceous. These gene losses are primarily concentrated in marine teleost fish and synchronous with the mid Cretaceous anoxic event, a period of rapid extinction for marine species. Finally, we reveal a mismatch between phylogenetic placement and gene nomenclature for up to 50% of TLRs found in clades such as ray-finned fishes, cyclostomes, amphibians, and elasmobranchs. Collectively, these results provide an unparalleled perspective of TLR diversity and offer a ready framework for testing gene annotations in non-model species.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":" ","pages":"465-478"},"PeriodicalIF":3.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9960738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunogeneticsPub Date : 2023-10-01Epub Date: 2023-07-05DOI: 10.1007/s00251-023-01313-9
Nicolas I E Rocos, Felicity J Coulter, Thomas C J Tan, Jim Kaufman
{"title":"The minor chicken class I gene BF1 is deleted between short imperfect direct repeats in the B14 and typical B15 major histocompatibility complex (MHC) haplotypes.","authors":"Nicolas I E Rocos, Felicity J Coulter, Thomas C J Tan, Jim Kaufman","doi":"10.1007/s00251-023-01313-9","DOIUrl":"10.1007/s00251-023-01313-9","url":null,"abstract":"<p><p>The chicken major histocompatibility complex (MHC, also known as the BF-BL region of the B locus) is notably small and simple with few genes, most of which are involved in antigen processing and presentation. There are two classical class I genes, of which only BF2 is well and systemically expressed as the major ligand for cytotoxic T lymphocytes (CTLs). The other class I gene, BF1, is believed to be primarily a natural killer (NK) cell ligand. Among most standard chicken MHC haplotypes examined in detail, BF1 is expressed tenfold less than BF2 at the RNA level due to defects in the promoter or in a splice site. However, in the B14 and typical B15 haplotypes, BF1 RNA was not detected, and here, we show that a deletion between imperfect 32 nucleotide direct repeats has removed the BF1 gene entirely. The phenotypic effects of not having a BF1 gene (particularly on resistance to infectious pathogens) have not been systematically explored, but such deletions between short direct repeats are also found in some BF1 promoters and in the 5' untranslated region (5'UTR) of some BG genes found in the BG region of the B locus. Despite the opposite transcriptional orientation of homologous genes in the chicken MHC, which might prevent the loss of key genes from a minimal essential MHC, it appears that small direct repeats can still lead to deletion.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":" ","pages":"455-464"},"PeriodicalIF":3.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10110766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunogeneticsPub Date : 2023-08-01DOI: 10.1007/s00251-023-01303-x
Mohamed Habib Yahyaoui
{"title":"Characterization and genetic diversity of MHC class II DRB genes in the Arabian camel (Camelus dromedarius).","authors":"Mohamed Habib Yahyaoui","doi":"10.1007/s00251-023-01303-x","DOIUrl":"https://doi.org/10.1007/s00251-023-01303-x","url":null,"abstract":"<p><p>This study investigated the MHC DRB genes in the Arabian camel (Camelus dromedarius). The results revealed the presence of - at least - two transcribed DRB-like genes in chromosome 20, designated MhcCadr-DRB1 and MhcCadr-DRB2. These genes are 155 Kb apart, have similar gene structure, and are transcribed in opposite directions. Compared to DRB1, the DRB2 locus contains a deletion of 12 nucleotides in the second exon (270 bp), exhibits lower transcript abundance, and is expressed as two splice variants differing by exon 2 skipping. This gene seems to be of minor functional relevance in the dromedary camel. Conversely, the DRB1 is thought to be the main gene in this species showing higher transcript abundance and polymorphism levels. A total of seven DRB1 exon 2 alleles were identified in the Tunisian dromedary camel resulting from 18 amino acid substitutions. Six full length alleles were characterized at the mRNA level. Although there is no clear evidence for balancing selection (i.e., heterozygote advantage), signals of weak historical positive selection acting on the DRB1 gene were detected, as indicated by the limited number of the sites being positively selected. This trend might be related to the low exposure to pathogens and to the demographic history of the species. Comparative analysis with Bactrian and wild camel genomes suggested occurrence of trans species polymorphism (TSP) in the Camelus genus. The results lay the foundation for the MHC DRB1 genetic diversity analysis in this genus since the developed genotyping protocols are fully applicable in the three Camelus species.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 4","pages":"355-368"},"PeriodicalIF":3.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10072047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10228222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunogeneticsPub Date : 2023-08-01DOI: 10.1007/s00251-023-01312-w
Nourelhoda E Hassan, Walaa A Moselhy, Ehab B Eldomany, Emad Farah Mohamad Kholef
{"title":"Correction to: Evaluation of miRNA-16-2-3P, miRNA-618 levels and their diagnostic and prognostic value in the regulation of immune response during SARS Cov-2 infection.","authors":"Nourelhoda E Hassan, Walaa A Moselhy, Ehab B Eldomany, Emad Farah Mohamad Kholef","doi":"10.1007/s00251-023-01312-w","DOIUrl":"https://doi.org/10.1007/s00251-023-01312-w","url":null,"abstract":"","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 4","pages":"411"},"PeriodicalIF":3.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10353949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10219466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunogeneticsPub Date : 2023-08-01Epub Date: 2023-04-21DOI: 10.1007/s00251-023-01305-9
Jeannine A Ott, Christian Mitchell, Morgan Sheppard, Thad C Deiss, J M Cody Horton, Jeremy K Haakenson, Ruiqi Huang, Abigail R Kelley, Brian W Davis, James N Derr, Vaughn V Smider, Michael F Criscitiello
{"title":"Evolution of immunogenetic components encoding ultralong CDR H3.","authors":"Jeannine A Ott, Christian Mitchell, Morgan Sheppard, Thad C Deiss, J M Cody Horton, Jeremy K Haakenson, Ruiqi Huang, Abigail R Kelley, Brian W Davis, James N Derr, Vaughn V Smider, Michael F Criscitiello","doi":"10.1007/s00251-023-01305-9","DOIUrl":"10.1007/s00251-023-01305-9","url":null,"abstract":"<p><p>The genomes of most vertebrates contain many V, D, and J gene segments within their Ig loci to construct highly variable CDR3 sequences through combinatorial diversity. This nucleotide variability translates into an antibody population containing extensive paratope diversity. Cattle have relatively few functional VDJ gene segments, requiring innovative approaches for generating diversity like the use of ultralong-encoding IGHV and IGHD gene segments that yield dramatically elongated CDR H3. Unique knob and stalk microdomains create protracted paratopes, where the antigen-binding knob sits atop a long stalk, allowing the antibody to bind both surface and recessed antigen epitopes. We examined genomes of twelve species of Bovidae to determine when ultralong-encoding IGHV and IGHD gene segments evolved. We located the 8-bp duplication encoding the unique TTVHQ motif in ultralong IGHV segments in six Bovid species (cattle, zebu, wild yak, domestic yak, American bison, and domestic gayal), but we did not find evidence of the duplication in species beyond the Bos and Bison genera. Additionally, we analyzed mRNA from bison spleen and identified a rich repertoire of expressed ultralong CDR H3 antibody mRNA, suggesting that bison use ultralong IGHV transcripts in their host defense. We found ultralong-encoding IGHD gene segments in all the same species except domestic yak, but again not beyond the Bos and Bison clade. Thus, the duplication event leading to this ultralong-encoding IGHV gene segment and the emergence of the ultralong-encoding IGHD gene segment appears to have evolved in a common ancestor of the Bos and Bison genera 5-10 million years ago.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 4","pages":"323-339"},"PeriodicalIF":2.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10119515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9851940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunogeneticsPub Date : 2023-08-01DOI: 10.1007/s00251-023-01304-w
Michael Levinson, Mohamed Khass, Peter D Burrows, Harry W Schroeder
{"title":"Germline-enforced enrichment for charged amino acids in TCR beta chain (TCRβ) complementarity determining region 3 (CDR-B3) alters T cell development, repertoire content, and antigen recognition.","authors":"Michael Levinson, Mohamed Khass, Peter D Burrows, Harry W Schroeder","doi":"10.1007/s00251-023-01304-w","DOIUrl":"https://doi.org/10.1007/s00251-023-01304-w","url":null,"abstract":"<p><p>T cell receptor beta chain (TCRβ) diversity (Dβ) gene segments are highly conserved across evolution, with trout Dβ1 sequence identical to human and mouse Dβ1. A key conserved feature is enrichment for glycine in all three Dβ reading frames (RFs). Previously, we found that replacement of mouse Dβ1 with a typical immunoglobulin D<sub>H</sub> sequence, which unlike Dβ is enriched for tyrosine, leads to an increase in the use of tyrosine in TCRβ complementarity determining region 3 (CDR-B3) after thymic selection, altering T cell numbers, CDR-B3 diversity, and T cell function. To test whether the incorporation of charged amino acids into the Dβ sequence in place of glycine would also influence T cell biology, we targeted the TCRβ locus with a novel glycine-deficient DβDKRQ allele that replaces Dβ1 coding sequence with charged amino acids in all three reading frames. Developing T cells using DβDKRQ expressed TCR CDR-B3s depleted of tyrosine and glycine and enriched for germline-encoded lysine, arginine, and glutamine. Total thymocytes declined in number during the process of β selection that occurs during the transition from the DN3bc to DN4 stage. Conventional thymocyte and T cell numbers remained reduced at all subsequent thymic stages and in the spleen. By contrast, regulatory T cell numbers were increased in Peyer's patches and the large intestine. In terms of functional consequences, T cell reactivity to an ovalbumin immunodominant epitope was reduced. These findings buttress the view that natural selection of Dβ sequence is used to shape the pre-immune TCRβ repertoire, affecting both conventional and regulatory T cell development and influencing epitope recognition.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 4","pages":"341-353"},"PeriodicalIF":3.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10209946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunogeneticsPub Date : 2023-08-01DOI: 10.1007/s00251-023-01308-6
Nourelhoda E Hassan, Walaa A Moselhy, Ehab B Eldomany, Emad Farah Mohamad Kholef
{"title":"Evaluation of miRNA-16-2-3P, miRNA-618 levels and their diagnostic and prognostic value in the regulation of immune response during SARS Cov-2 infection.","authors":"Nourelhoda E Hassan, Walaa A Moselhy, Ehab B Eldomany, Emad Farah Mohamad Kholef","doi":"10.1007/s00251-023-01308-6","DOIUrl":"https://doi.org/10.1007/s00251-023-01308-6","url":null,"abstract":"<p><p>Following the announcement of the pandemic of COVID-19 in December 2019, several studies focused on how to early predict the severity of the disease in symptomatic and asymptomatic patients. Many cytokines including interleukin-6, interleukin-8, and tumor necrotic factors have been concluded as strong indicators for COVID-19 infection. Additionally, miRNAs have been associated with dysregulation in the immune system. The aim of this study are the following: (1) to estimate the level of miRNA-16-2-3P, miRNA-618, IL-8, IL-1β as predictors for SARS-CoV-2 complications in PCR negative and positive patients; (2) to assess the biological role and effect of these miRNAs on SARS-CoV-2 pathogenicity. Our study showed that the level of IL-1β had been significantly associated with patient who need hospitalization, also the alteration of the level of miRNA-16-2-3P, miRNA-618 is positively correlated with the admission of these patients and influence the outcomes of SARS-cov-2 infection. Measurement of miRNA-16-2-3P, miRNA-618, IL-1β could be a good predictor of COVID-19 patient outcome. However the measurement of IL-8 levels during immune responses in the admitted and in ICU patients could have a prognostic value.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 4","pages":"403-410"},"PeriodicalIF":3.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10206366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9852707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prognostic value of the WT-1 gene combined with recurrent cytogenetic genes in acute myeloid leukemia.","authors":"Qing Zhang, Linlin Liu, Haotian Yan, Xiyang Ren, Mei Zhou, Shudao Xiong, Huiping Wang, Qianshan Tao, Zhimin Zhai","doi":"10.1007/s00251-023-01314-8","DOIUrl":"https://doi.org/10.1007/s00251-023-01314-8","url":null,"abstract":"<p><p>Wilms tumor gene 1 (WT-1 gene) is overexpressed in most patients with acute myeloid leukemia (AML) and is an indicator for minimal residual disease (MRD) monitoring, but because the WT-1 gene has relatively low specificity, further studies of the prognostic value of a combination of the WT-1 and other genes are needed. The aim of this study was to explore the prognostic value of the WT-1 gene combined with recurrent cytogenetic genes in AML. In AML, the transcript expression of the WT-1 gene was closely related to leukemic tumor burden and acted as an accurate molecular indicator for MRD detection. Most patients with low expression levels of the WT-1 gene after induction and consolidation therapy were significantly associated with favorable relapse-free survival (RFS) and overall survival (OS), but 17.6% of patients relapsed and died of primary disease. However, when analyzing the WT-1 gene combined with recurrent cytogenetic genes, none of the patients with low expression levels of the WT-1 gene and recurrent cytogenetic genes negative relapsed and died in the median follow-up time of 19 months (range: 3-94 months). Thus, the combination of the WT-1 gene and recurrent cytogenetic genes is a more accurate indicator for MRD monitoring and prognosis evaluation in AML patients.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 4","pages":"395-401"},"PeriodicalIF":3.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9851972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}