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Chlamydia trachomatis incidence in relation to vaginal microbiota dynamics, immunogenetics and exposures in a cohort of young student women in France.

BACKGROUND: Given the potential role of the vaginal microbiota in the acquisition of Chlamydia trachomatis infections, we aim to investigate its contribution together with immunogenetics and epidemiological exposures to the incidence of C. trachomatis in young women. METHODS: This study involved 313 female students aged 18-24 years from the i-Predict prevention trial in France. Participants provided four self-collected vaginal samples and filled four self-administered questionnaires every 6 months for 18 months. C. trachomatis-positive participants and negative controls with complete follow-up were selected for this analysis and submitted to chlamydia testing and to vaginal microbiota characterization using 16S rRNA amplicon sequencing. Thirteen human single nucleotide polymorphisms (SNPs) related to C. trachomatis susceptibility and severity were also assessed. RESULTS: Compared to 260 non-infected participants, Gardnerella spp., Fannyhessea vaginae and Prevotella timonensis were more abundant in C. trachomatis-incident participants (n=24) before infection. Having a CST IV at the preceding sample compared to a CST I (3.56 [1.08-11.70], p=0.037) was associated with increased risk of C. trachomatis acquisition, as well as having had multiple concomitant partners in the last 6 months (4.33 [1.19-15.72], p=0.028). Lifetime condom use was associated with decreased incidence (OR 0.38 [0.16-0.94], p=0.037). None of the tested human SNPs was associated with C. trachomatis infection. CONCLUSIONS: In this low-risk for C. trachomatis population, having a CST IV-AB vaginal microbiota and associated bacterial anaerobes was a risk factor for C. trachomatis acquisition after adjustment for other exposures. Condom use remains one of the main tools to prevent incidence.

C. trachomatis↗

IMGT, the international ImMunoGeneTics database.

IMGT, the international ImMunoGeneTics database (http://imgt.cines. fr:8104 ), is a high-quality integrated database specialising in Immunoglobulins (Ig), T cell Receptors (TcR) and Major Histocompatibility Complex (MHC) molecules of all vertebrate species, created in 1989 by Marie-Paule Lefranc, Université Montpellier II, CNRS, Montpellier, France (lefranc@ligm.igh.cnrs.fr ). At present, IMGT includes two databases: IMGT/LIGM-DB, a comprehensive database of Ig and TcR from human and other vertebrates, with translation for fully annotated sequences, and IMGT/HLA-DB, a database of the human MHC referred to as HLA (Human Leucocyte Antigens). The IMGT server provides a common access to expertized genomic, proteomic, structural and polymorphic data of Ig and TcR molecules of all vertebrates. By its high quality and its easy data distribution, IMGT has important implications in medical research (repertoire in autoimmune diseases, AIDS, leukemias, lymphomas), therapeutic approaches (antibody engineering), genome diversity and genome evolution studies. IMGT is freely available at http://imgt.cines.fr:8104. The IMGT Index is provided at the IMGT Marie-Paule page (http://imgt.cines.fr:8104/textes/IMGTindex.html).

Amino Acid Sequence↗

IMGT, the international ImMunoGeneTics database.

The international ImMunoGeneTics database (IMGT) (http://imgt.cines.fr), is a high quality integrated information system specializing in Immunoglobulins (IG), T cell Receptors (TR) and Major Histocompatibility Complex (MHC) of human and other vertebrates, created in 1989, by the Laboratoire d'ImmunoGénétique Moléculaire (LIGM), at the Université Montpellier II, CNRS, Montpellier, France. IMGT provides a common access to standardized data which include nucleotide and protein sequences, oligonucleotide primers, gene maps, genetic polymorphisms, specificities, 2D and 3D structures. IMGT includes three sequence databases (IMGT/LIGM-DB, IMGT/MHC-DB, IMGT/PRIMER-DB), one genome database (IMGT/GENE-DB) with different interfaces (IMGT/GeneSearch, IMGT/GeneView, IMGT/LocusView), one 3D structure database (IMGT/3Dstructure-DB), Web resources comprising 8000 HTML pages ('IMGT Marie-Paule page') and interactive tools for sequence analysis (IMGT/V-QUEST, IMGT/JunctionAnalysis, IMGT/Allele-Align, IMGT/PhyloGene). IMGT data are expertly annotated according to the rules of the IMGT Scientific chart, based on IMGT-ONTOLOGY. IMGT tools are particularly useful for the analysis of the IG and TR repertoires in physiological normal and pathological situations. IMGT has important applications in medical research (autoimmune diseases, AIDS, leukemias, lymphomas, myelomas), biotechnology related to antibody engineering (phage displays, combinatorial libraries) and thera-peutic approaches (graft, immunotherapy). IMGT is freely available at http://imgt.cines.fr.

Animals↗

Hepatitis B epidemiology and its relation to immunogenetic traits in South American Indians.

Serologic tests for hepatitis B prevalence and immunogenetic characterizations were carried out on a sample of 800 persons from several isolated tribes of the lower Amazon basin and the southern Andes. The prevalence of hepatitis B antigen carriers and of antibody to the surface antigen varied from one tribe to another, but were high in all the forest tribes. The serologic evidence indicated high infection rates early in life, but also an increasing proportion showing evidence of infection with increasing age. The frequency of past infections was not differentially associated with the antigen status of the mother or father. A higher proportion of infected males than females had antigenemia. Contrary to published reports, no association of antigenemia was found with any HLA-A, B or C antigen or immunoglobulin allotype, individually or interactively. Antibody prevalence, however, did differ in persons with different HLA haplotypes.

Adolescent↗

Immunogenetics of the A-E alloantigen complex.

The close linkage (0.5%) between the A and E erythrocyte alloantigen loci present a special challenge in the production of locus-specific typing antisera. The objective of the investigation was to determine immunogenetically the A-E haplotypes (genetically linked combinations of A and E antigens) existing in the locally maintained individuals of the New Hampshire (NH) and White Plymouth Rock (WR) breeds. The A and E alloantigens in these populations were identified using reference antisera previously produced in White Leghorns. A total of four A-E haplotypes were identified within each of the two breeds; A2E1, A6E2, A6E4, and A8E2 in WR and A2E1, A3E7, A7E4, and A8E2 in NH. Individuals of these two brown-egg breeds were backcrossed over several generations to a line of Ancona chickens homozygous at the A and E loci. Genetic segregation occurring over four generations resulted in nonrecombinant and recombinant progeny that were immunized reciprocally with the blood of siblings to raise antibodies reactive with the individual A and E antigens of the NH and WR stocks. The antisera resulting from the within-family alloimmunizations confirmed the haplotypes deduced in the WR and NH lines from the initial tests with the A and E reference antisera.

Animals↗

Immunogenetic heterogeneity in rheumatoid disease as illustrated by different MHC associations (DQ, Dw and C4) in articular and extra-articular subsets.

Genetic variants at DRB1 (Dw subtypes), DQB, and C4 loci were compared in rheumatoid disease subjects with or without the extra-articular feature of Felty's syndrome or major vasculitis. DR4 positive subjects with rheumatoid arthritis alone showed no preferential associations with DQB or Dw variants or with C4 null alleles. Felty's subjects showed associations with the DQB encoded DQw7 allele and with the C4B null allele but no preferential associations with any Dw subtype of DR4. By contrast DR4 +ve rheumatoid-vasculitic subjects showed associations with the Dw14 as well as with DQw7 and the C4A null allele. These different MHC associations in different clinical disease subsets show that rheumatoid disease is immunogenetically heterogeneous and suggest that MHC genes outside the DRB1 locus may also influence susceptibility or modify expression of the rheumatoid disease process.

Alleles↗

Calcinosis and the anticentromere antibody: its clinical, radiological and immunogenetic aspects.

The relationship between calcinosis and the anticentromere antibody (ACA) was studied from a clinical, radiological and immunogenetic standpoint. Ten ACA-positive scleroderma patients, 34 ACA-negative scleroderma patients, 31 ACA-positive patients without sclerodermatous skin changes and 140 ACA-negative patients with various rheumatic diseases were compared with regard to the incidence of calcinosis as measured by radiographs of hand and/or foot. Calcinosis was found in 10 (100%), 12 (35%), 13 (42%) and eight (6%) patients in each group respectively. Frequent sites for calcinosis in the ACA-positive patients were foot (24%), hand (21%) and leg (19%). The forearm was not usually involved (6%). During the follow-up term (1.0-9.5 years; mean 4.5 years) of 11 ACA-positive patients without calcinosis, four (36%) developed new calcinosis and this incidence was significantly higher (P less than 0.02) than that in the ACA-negative control group (2/42; 4.8%). As a whole, 23 (59%) of 39 patients with ACA showed calcinosis. In the ACA-positive patients with calcinosis, sclerodactyly (P less than 0.005) and CREST syndrome (P less than 0.001) were found more frequently than in ACA-positive patients without calcinosis. HLA-A2 was found more frequently (67%) in the ACA-positive patients with calcinosis when compared to normal subjects (41%) (P less than 0.02). We concluded that calcinosis seems closely related to scleroderma, especially those with ACA, and that the development of calcinosis requires a certain genetic background.

Antibodies↗

Cytokine and immunogenetic profiles in Japanese patients with adult Still's disease. Association with chronic articular disease.

OBJECTIVE: To determine cytokines and MHC class II alleles in Japanese patients with adult Still's disease (ASD) and clarify the association between those profiles and chronic articular disease. METHODS: Of 35 patients with ASD (13 men, 22 women, mean age at onset 34.0 yr), 17 (49%) had chronic arthritis (>6 months, chronic articular ASD) and 18 (51%) lacked chronic arthritis (systemic ASD). Cytokines and cytokine receptors in sera were measured by ELISA. Correlations of each cytokine with disease activity or C-reactive protein (CRP) were determined. MHC class II alleles were examined by polymerase chain reaction methods. RESULTS: In chronic articular ASD, female gender was more frequent and liver dysfunction and myalgia were rarer than in systemic ASD. In active disease, the white blood cell count was lower, but total IgG was greater in patients with chronic articular ASD than in those with systemic ASD. Tumour necrosis factor (TNF) alpha, soluble TNF receptor 2 and interleukin (IL)-18 were increased in both types of ASD, even in remission. Soluble IL-2 receptors, IL-4 and IL-18 levels were correlated with disease activity or CRP value only in chronic articular ASD. Interferon gamma and IL-8 remained increased only in chronic articular ASD, even when disease activity, including IL-6 and CRP, was low. DRB1*1501 (DR2) and DRB1*1201 (DR5) alleles were more frequent in chronic articular than in systemic ASD, whereas DQB1*0602 (DQ1) was frequently observed in both types of ASD. CONCLUSION: The present study suggests that ASD with chronic articular disease has distinct clinical, cytokine and immunogenetic profiles.

Adult↗

Immunogenetics of the spondyloarthropathies.

In this review, recent data relevant to better understanding of the immunogenetics of the spondyloarthropathies are discussed or, in a somewhat broader sense, the HLA-B27 disease associations. Although in 1993 much more is known about the B27 molecule than was known in 1992, its contribution to the pathogenesis of disease is unclear. Peptide presentation to the T-cell receptor is still the basic, if not the only, function of HLA class I molecules. Nothing special was found for the B27 gene, molecule assembly, protein sequence, and crystal and peptide-binding motif, nor for the function dependent on these physical properties. Nevertheless, the theory regarding an "arthritogenic peptide" seemed to promise an explanation. However, this theory is rather an assembly of older views modified by the new data and is missing any detail or perspective that would answer the specific question: why B27 and not other HLA molecule(s)? If the solution is simple, and B27 is qualified to bind certain (bacterial) peptides that are not bound by any other class I molecule, or the unique complex, B27 + x, has special properties resulting in a "dysfunction," there is still no answer to the question: which peptide and why does its binding with B27 result in disease?

Animals↗

Familial predisposition to discogenic low-back pain. An epidemiologic and immunogenetic study.

The first-degree relatives (parents, siblings and children) of 284 patients complaining of discogenic low-back pain (Group I), 114 patients who had undergone surgery for lumbar disc herniation (Group II), and 280 individuals who had never complained of low-back pain (Group III) were surveyed by self-completed questionnaires. Of the families in Group I and Group II, 35 and 37%, respectively, had at least one member with a history of discogenic back pain and 5 and 10%, respectively, had one or two members who had undergone disc surgery. Of the asymptomatic subjects in Group III, only 12% had at least one or more affected relatives and 1% had a relative who had undergone disc surgery; of the affected families, 41% had two or more members with a history of back pain. The proportion of symptomatic relatives in the affected families was higher among sedentary workers and motor vehicle drivers than among heavy or light manual workers. An immunogenetic study comparing the frequencies of HLA-A, B, and C antigens in 39 patients who had undergone lumbar disc surgery with those in 60 asymptomatic individuals showed no significant differences between the two groups. This study indicates that there is a strong familial predisposition to discogenic low-back pain, and suggests that the etiology of degenerative disc disease is related to both genetic factors, not linked to the HLA antigen system, and environmental factors.

Adult↗

Studies on the antigenicity of vital allogeneic valve leaflet transplants in immunogenetically controlled strain combinations.

The use of defined inbred strains of rats enables reproducible experimentation on the antigenicity of heart valve leaflet transplantation. The inbred strains CAP, F344, and LEW were used as syngeneic, weakly allogeneic (RT-1-identical) and strongly allogeneic (RT-1-incompatible) strain combinations. After heart valve leaflet transplantation, humoral and cell-mediated immune responses were investigated. The results were: (1) Allogeneic heart valve leaflets are antigenic. (2) Just one heart valve leaflet, applied intravascularly induces sensitization of the recipient. (3) In the weakly allogeneic system, sensitization is only revealed by donor-specific skin transplants, while in the strongly allogeneic group, sensitization is demonstrated humorally as well. (4) The greater the immunogenetical difference, the sooner sensitization appears. In the strongly allogeneic system, skin transplants were rejected as "white grafts".

Animals↗

Joint report of the Third International Workshop on Canine Immunogenetics. I. Analysis of homozygous typing cells.

The Third International Workshop on Canine Immunogenetics involved 80 potentially DLA-D homozygous typing cells obtained from dogs of various breeds and submitted from five laboratories in Europe and the United States. Mutual reactivity of all cells was studied in mixed leukocyte cultures, and stabilized relative responses were used for analysis. Intralaboratory and interlaboratory comparisons of results suggest that a stabilized relative response of 30% represents an acceptable parameter for "typing responses" indicating phenotypic DLA-D identity of stimulator and responder cells. Using this criterion, 10 clusters of homozygous typing cells were defined and accepted on an international level, and they were assigned the specificities Dw1 to Dw10. At least six additional (provisional) specificities were recognized that were well characterized within individual laboratories but require additional testing before workshop specificities can be assigned. These data show that DLA-D typing is feasible and represents a useful tool in the genetic analysis of the canine major histocompatibility complex. Much work is needed to confirm the present results in family studies, to determine gene frequencies, and to analyze at a molecular level the antigens responsible for mixed leukocyte culture reactivity.

Animals↗

Orthotopic corneal transplantation in mice--evidence that the immunogenetic rules of rejection do not apply.

The fate of orthotopic corneal transplants has been studied in inbred strains of mice. Using a surgical technique that achieves > 95% success of syngeneic cornea grafts, it was determined that a high proportion of orthotopic cornea allografts were accepted indefinitely, irrespective of the degree of immunogenetic disparity between graft donor and recipient. Grafts that succumbed to irreversible rejection developed extensive corneal edema and intrastromal neovascularization as harbingers of corneal opacity and endothelial cell failure. The highest rate of rejection occurred among grafts that confronted their hosts with multiple minor histocompatibility antigens, with or without major histocompatibility antigens. Much lower rates of rejection (< 35%) were observed when the donors of the grafts differed from recipients at class I and/or class II major histocompatibility loci. Corneal grafts that confronted their hosts with class II MHC alloantigens alone experienced early, acute inflammation, and eventually developed stomal neovascularization, but only a small minority of these grafts were eventually destroyed. Allogeneic corneas that were transplanted orthotopically into eyes of presensitized mice were uniformly subjected to an acute rejection process that produced opacity within three weeks; however, in a minority of instances, the inflammation and opacity subside, and after eight weeks the grafts displayed a clear, nonvascularized appearance. The high rate of success of even grossly histoincompatible orthotopic corneal allografts in mice resembles the extraordinary success of unmatched allogeneic corneas transplanted into human eyes. The results are discussed in terms of the possible mechanisms that permit orthotopic corneal allografts to enjoy significantly better survival than orthotopic grafts of other types of solid tissues.

Animals↗

Immunogenetics of HTLV-I/II and associated diseases.

The ethnic background of human T-lymphotropic virus types I and II (HTLV-I/II) infections and associated diseases was investigated in association with human leukocyte antigens (HLA) (alleles) and haplotypes. Japanese HTLV-I carriers were characterized by two categories of HLA class I antigens (A24, A26, B7, B61, Cw1, and Cw7) and class II alleles (DRB1 *0101, 0803, 1403, 1501, and 1502 and DQB1 *0303, 0501, and 0601); one category was associated with adult T-cell leukemia (ATL) patients and the other with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients. The ATL-associated haplotypes had unique DRB1-DQB1 alleles (0901-0303, 1501-0602, 1401-0503), which were correlated with a low immune responsiveness to HTLV-I, while the HAM/TSP haplotypes had different DRB1-DQB1 alleles (0101-0501, 0803-0601, 1502-0601), which were correlated with a high immune responsiveness to HTLV-I. Both ATL- and HAM/TSP-associated haplotypes were found among HTLV-I carriers and the patients from other ethnic groups (Jamaican blacks, Andes natives, South American mestizos, and Mashhadi Jews). HLA haplotypes of HTLV-II carriers were different from those of HTLV-I carriers among South American natives. These results suggested that HTLV-I/II infections and the associated diseases might be determined by immunogenetic factors segregated with HLA alleles and haplotypes.

Carrier State↗

Non-HLA immunogenetic polymorphisms and the risk of complications after allogeneic hemopoietic stem-cell transplantation.

BACKGROUND: Existing data indicate that non-human leukocyte antigen (HLA) immunogenetic polymorphisms influence the risk of complications after allogeneic hemopoietic stem-cell transplantation. However, prior studies have been limited by small sample size and limited genotyping. METHODS: We examined 22 polymorphisms in 11 immunoregulatory genes including cytokines, mediators of apoptosis, and host-defense molecules by polymerase chain reaction using sequence-specific primers in 160 related myeloablative transplants. Associations were confirmed in two independent cohorts. RESULTS: An intronic polymorphism in the tumor necrosis factor gene (TNF 488A) was associated with the risk of acute graft-versus-host disease (GVHD) (odds ratio [OR] 16.9), grades II to IV acute GVHD (OR 3.3), chronic GVHD (OR 12.5), and early death posttransplant (OR 3.4). Recipient Fas -670G and donor interleukin (IL)-6 -174G were independent risk factors for acute GVHD. Recipient IL-10 ATA and Fas -670 genotype were independent risk factors for chronic GVHD. Recipient IL-1beta +3953T was associated with hepatic acute GVHD, and Fas -670G was associated with major infection. CONCLUSIONS: These results highlight the potential importance of cytokine and apoptosis gene polymorphisms in stem-cell transplantation, and indicate that non-HLA genotyping may be useful to identify individuals at the highest risk of complications and new targets for therapeutic intervention.

Adult↗

Neonatal lupus erythematosus: a review of the racial differences and similarities in clinical, serological and immunogenetic features of Japanese versus Caucasian patients.

There has been tremendous interest in neonatal lupus erythematosus (NLE) since the reports of anti-Ro/SSA antibodies as a diagnostic marker. Recent studies, including ours, have revealed racial differences as well as similarities in the clinical features and immunogenetic backgrounds of Japanese and Caucasian patients with NLE. The frequency of photosensitivity and subacute cutaneous LE lesions is not high in Japanese infants with NLE, which is in sharp contrast to their Caucasian American counterparts. The majority of Japanese infants with NLE develop annular, erythematous or edematous lesions which have also been reported in association with Sjögren's syndrome. The frequency of isolated congenital heart block (CHB) is about 50% in Japanese anti-Ro/SSA positive neonatal lupus infants; this is similar to the frequency among Caucasians. The HLA-DR3 phenotype, which is found in the great majority of Caucasian mothers of NLE infants, is absent in Japanese mothers. Finally, both Japanese and Caucasian children with CHB are often identical to their mothers in their alleles of HLA-DRB1, DQA1 and DQB1 loci.

Asian People↗

Immunogenetic analysis of tolerance induction in anti-alloantigen delayed type hypersensitivity responses by portal venous pre-inoculation with allogeneic cells.

The present study investigates some of the immunogenetic bases for tolerance of anti-allo-delayed type hypersensitivity (DTH) responses as induced by pre-inoculating allogeneic cells via portal venous (p.v.) route. BALB/c mice were injected with totally allogeneic C57BL/6 or H-2 incompatible BALB.B spleen cells via p.v. route. These mice not only failed to exhibit anti-H-2b DTH responses, but also abrogated the potential to generate H-2b-specific DTH responses as induced by the subsequent immunization with H-2b spleen cells via subcutaneous (s.c.) route. The p.v. presensitization with allogeneic spleen cells differing at either class I or class II of major histocompatibility complex (MHC) resulted in the tolerance induction of DTH responses to the respective allogeneic class I or class II MHC antigens. Moreover, the p.v. administration of the class I-positive allogeneic cell fraction depleted of class II-positive component into recipients differing at both class I and class II was capable of inducing anti-class I DTH tolerance. These results indicate that anti-allo-class I or class II DTH tolerance can be induced independently and that the existence of class II antigens on p.v.-presensitized cells is not necessarily required for the tolerance induction of anti-allo-class I DTH response.

Animals↗

Immunogenetics of Graves' ophthalmopathy.

We have performed an immunogenetic analysis of 53 patients with severe Graves' ophthalmopathy, 51 patients with Graves' disease but little or no clinically apparent eye disease, and 90 controls. The distribution of restriction fragment length polymorphisms was analysed in the three groups, using probes for the HLA-DQ alpha and DR beta regions, the T-cell receptor C alpha, V alpha, C beta and J gamma genes and the immunoglobulin gene switch regions, S alpha and S mu. There was no abnormal distribution of these polymorphisms in either group of Graves' patients, or differences between the Graves' patients with or without eye disease. It was possible to assign HLA-DR types in most patients using the polymorphisms found after probing with DQ alpha and DR beta; there was no abnormal distribution of DR types (including HLA-DR3) assigned by restriction fragment polymorphisms in the two Graves' groups. These results fail to confirm the reported associations between ophthalmopathy and HLA-DR3 and between Graves' disease and the T-cell receptor C beta polymorphism; they also argue against a strong influence of Gm allotypes in Graves' disease since these genes are in linkage disequilibrium with the S alpha polymorphisms. The association of Graves' disease with HLA-DR3, defined hitherto using serological reagents, may be less strong than previously described.

Graves Disease↗