Immunogenetic basis of acquired transplantation tolerance.
Explore the source record for details and available documents.
Animals↗
SEARCH · Search PubMed
Results for “immunogenetics”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Immunogenetic aspects of transplantation in the rat brain.
The nature of the brain as an immunologically privileged site is controversial. Using congenic rats, we have demonstrated that grafts that differ from the recipient in the A locus of the MHC produce sensitization following intracerebral transplantation, thus indicating that the brain is not immunologically privileged. The IC grafts show histologic signs of rejection, which are delayed compared with the changes found in the subsequent orthotopic grafts, suggesting that the immune response is weaker in the brain.
Animals↗
Immunogenetic and clinical factors affecting renal transplantation. A rigorous analysis of data recorded by the UK Transplant Service.
A total of 3653 first cadaver kidney transplants in nondiabetic recipients over 15 years of age, performed in 30 transplant centers throughout the United Kingdom between 1978 and 1983, were analyzed to discover which of many recorded recipient, donor, surgical, and tissue-matching variables were important for graft survival, and in which postoperative period they exerted their maximum influence. A considerable effort was invested in checking the validity of the data and the appropriateness of the statistical methods. The duration of dialysis prior to transplantation was associated with a substantially reduced risk of graft failure, particularly at later postoperative times. Good HLA-B locus matching was also found to enhance graft survival--but, by contrast, HLA-A locus matching showed no significant effect on survival. Recipient age over 45 years, high serum reactivity, and grafts with anoxia time (the interval between circulatory arrest and perfusion with ice) exceeding 10 min were found to be associated with poor graft survival. Trends in survival were identified across calendar years of transplant, such that early graft failure (0-15 days) had increased in recent years, whereas later graft failure (greater than 15 days) had declined.
Adolescent↗
Joint report of the Third International Workshop of Canine Immunogenetics. II. Analysis of the serological typing of cells.
Using a standardized microlymphocytotoxicity assay, seven international laboratories evaluated 144 anti-dog lymphocyte antigen (DLA) sera in 319 mixed breed and 152 Beagle dogs. The workshop confirmed the serological definitions for DLA-A2, A3, A9; DLA-B4, B5, B6, B13; DLA-C11(Cwl); and C12(Cw2). Two new specificities were assigned to the DLA-A locus (Aw14 and Aw15) in only the mixed breed dogs. A third specificity (Cw3), was assigned to the DLA-C locus. The antigen and gene frequencies of these alleles differed between the two groups of dogs, but the frequencies of the "blank" were similar in both groups. Future international collaborations will be necessary to definite more completely the polymorphisms of the major histocompatibility complex (MHC) of the dog. Those efforts will benefit from the standard serological test established in this workshop.
Alleles↗
Immunohistochemical analyses of skin graft rejection in mice. Kinetics of lymphocyte infiltration in grafts of limited immunogenetic disparity.
We have examined the nature and kinetics of T cell infiltration into murine first-set skin allografts across a variety of histocompatibility differences. Both Ly 1+2- and Ly 2+ cells migrate into grafts that differ with respect to discrete class I, class II, or minor H barriers. The lymphoid cells in the allograft did not express MEL 14 or the B cell antigen B220. The cells in the graft progress from the vascular anastomosis region into the dermis with apparent homing and clustering about hair follicles and epithelial cells at the dermoepidermal junction. Microscopic necroses appear in a patchy distribution in these areas. The intensity of the infiltrate is related to the nature of the alloantigen recognized but it does not correlate with the tempo of rejection. Class II-disparate allografts evoke a peak response (mean 62 +/- 34 T cells/0.1 mm2) that is 2-6-fold greater than class I-disparate allografts or syngeneic control peak responses (mean 14 +/- 2.4 T cells/0.1 mm2). Although a difference at a minor H antigen evoked an intense peak T cell response (192 +/- 33 T cells/0.1 mm2), the mean survival time of the allografts was significantly longer than that observed with class I or class II differences. The IL-2 receptor+ subset of activated T cells is extremely rare in syngeneic grafts, but ranges from 0 to 56% of infiltrating T cells in allografts. We conclude that all major T cell subsets contribute to the in situ response to all classes of alloantigens, but at the apparent exclusion of the MEL 14+ T cell pool and B cells.
Animals↗
Multicenter evaluation of the flow cytometry T-cell crossmatch: results from the American Society of Histocompatibility and Immunogenetics-College of American Pathologists proficiency testing program.
BACKGROUND: The performance characteristics and interlaboratory comparisons of the T-cell flow cytometry crossmatch remain largely unknown. METHODS: This study was performed using data from the ASHI-CAP proficiency testing program. Four unknown sera and two unknown cells were sent to participating laboratories twice a year for 4 years. RESULTS: In one survey in which different crossmatch techniques were compared, flow cytometry was slightly more sensitive than the antiglobulin method and considerably more sensitive than direct cytotoxicity. However, the proportion of participants in any given survey detecting antibodies in all sera expected to be positive was 50-60% and has not changed over the years. Failure to detect antibodies correlated with low antibody concentration, diluting the unknown serum by the testing laboratory, and with the instrument used. False positive results with normal sera were infrequent. Fluorescence intensity values were not standardized and were highly variable, but when fluorescence units reported by individual laboratories were divided by their own positive-negative cutoff values, results from different centers were more comparable. In general, fluorescence-to-cutoff ratios >5 correlated with complement binding activity, whereas values <5 denoted concentrations below those required to fix complement. CONCLUSIONS: Flow cytometry, as used by most centers, is highly sensitive and allows relative antibody quantitation. Furthermore, the data define objective parameters that may help to standardize the test and improve its predictive value in clinical transplantation.
Antibodies↗
New insights into the immunogenetics of multiple sclerosis.
The genetic analysis of multiple sclerosis has been based mainly on candidate gene association studies in selected populations. However, the candidate gene approach, although straightforward, is problematic in diseases of unknown or partially known etiology. With the advent of genomic screening and novel statistical approaches, it is possible now to perform an efficient screen of the entire human genome to identify the genetic components of multiple sclerosis.
Humans↗
Clinical and immunogenetic correlates of abacavir hypersensitivity.
A patch test (PT) may be useful in defining true abacavir hypersensitivity syndrome (AHS). Seven previously PT-positive patients remote from the original AHS were shown to have robust 24 h responses, supporting PT durability. HLA-B*5701 was present in all seven PT-positive versus one of 11 controls tolerating abacavir (P < 0.001). Five of seven PT (71%) versus one of 11 controls (9%) (P = 0.005) showed significant abacavir-specific CD8 proliferation, suggesting a direct role for HLA-B*5701-restricted CD8 cells in the pathophysiology of AHS.
Anti-HIV Agents↗
Immunogenetic risk and protective factors for the idiopathic inflammatory myopathies: distinct HLA-A, -B, -Cw, -DRB1 and -DQA1 allelic profiles and motifs define clinicopathologic groups in caucasians.
The idiopathic inflammatory myopathies (IIM) are systemic connective tissue diseases in which autoimmune pathology is suspected to promote chronic muscle inflammation and weakness. We have performed low to high resolution genotyping to characterize the allelic profiles of HLA-A, -B, -Cw, -DRB1, and -DQA1 loci in a large population of North American Caucasian patients with IIM representing the major clinicopathologic groups (n = 571). We confirmed that alleles of the 8.1 ancestral haplotype were important risk markers for the development of IIM, and a random forests classification analysis suggested that within this haplotype, HLA-B*0801, DRB1*0301 and/ or closely linked genes are the principal HLA risk factors. In addition, we identified several novel HLA factors associated distinctly with 1 or more clinicopathologic groups of IIM. The DQA1*0201 allele and associated peptide-binding motif (KLPLFHRL) were exclusive protective factors for the CD8+ T cell-mediated IIM forms of polymyositis (PM) and inclusion body myositis (IBM) (pc < 0.005). In contrast, HLA-A*68 alleles were significant risk factors for dermatomyositis (DM) (pc = 0.0021), a distinct clinical group thought to involve a humorally mediated immunopathology. While the DQA1*0301 allele was detected as a possible risk factor for IIM, PM, and DM patients (p < 0.05), DQA1*03 alleles were protective factors for IBM (pc = 0.0002). Myositis associated with malignancies was the most distinctive group of IIM wherein HLA Class I alleles were the only identifiable susceptibility factors and a shared HLA-Cw peptide-binding motif (AGSHTLQWM) conferred significant risk (pc = 0.019). Together, these data suggest that HLA susceptibility markers distinguish different myositis phenotypes with divergent pathogenetic mechanisms. These variations in associated HLA polymorphisms may reflect responses to unique environmental triggers resulting in the tissue pathospecificity and distinct clinicopathologic syndromes of the IIM.
Adult↗
Immunogenetic risk and protective factors for the idiopathic inflammatory myopathies: distinct HLA-A, -B, -Cw, -DRB1, and -DQA1 allelic profiles distinguish European American patients with different myositis autoantibodies.
The idiopathic inflammatory myopathies (IIM) are systemic connective tissue diseases defined by chronic muscle inflammation and weakness associated with autoimmunity. We have performed low to high resolution molecular typing to assess the genetic variability of major histocompatibility complex loci (HLA-A, -B, -Cw, -DRB1, and -DQA1) in a large population of European American patients with IIM (n = 571) representing the major myositis autoantibody groups. We established that alleles of the 8.1 ancestral haplotype (8.1 AH) are important risk factors for the development of IIM in patients producing anti-synthetase/anti-Jo-1, -La, -PM/Scl, and -Ro autoantibodies. Moreover, a random forests classification analysis suggested that 8.1 AH-associated alleles B*0801 and DRB1*0301 are the principal HLA risk markers. In addition, we have identified several novel HLA susceptibility factors associated distinctively with particular myositis-specific (MSA) and myositis-associated autoantibody (MAA) groups of the IIM. IIM patients with anti-PL-7 (anti-threonyl-tRNA synthetase) autoantibodies have a unique HLA Class I risk allele, Cw*0304 (pcorr = 0.046), and lack the 8.1 AH markers associated with other anti-synthetase autoantibodies (for example, anti-Jo-1 and anti-PL-12). In addition, HLA-B*5001 and DQA1*0104 are novel potential risk factors among anti-signal recognition particle autoantibody-positive IIM patients (pcorr = 0.024 and p = 0.010, respectively). Among those patients with MAA, HLA DRB1*11 and DQA1*06 alleles were identified as risk factors for myositis patients with anti-Ku (pcorr = 0.041) and anti-La (pcorr = 0.023) autoantibodies, respectively. Amino acid sequence analysis of the HLA DRB1 third hypervariable region identified a consensus motif, 70D (hydrophilic)/71R (basic)/74A (hydrophobic), conferring protection among patients producing anti-synthetase/anti-Jo-1 and -PM/Scl autoantibodies. Together, these data demonstrate that HLA signatures, comprising both risk and protective alleles or motifs, distinguish IIM patients with different myositis autoantibodies and may have diagnostic and pathogenic implications. Variations in associated polymorphisms for these immune response genes may reflect divergent pathogenic mechanisms and/or responses to unique environmental triggers in different groups of subjects resulting in the heterogeneous syndromes of the IIM.
Alleles↗
Immunogenetics of leishmanial and mycobacterial infections: the Belem Family Study.
In the 1970s and 1980s, analysis of recombinant inbred, congenic and recombinant haplotype mouse strains permitted us to effectively 'scan' the murine genome for genes controlling resistance and susceptibility to leishmanial infections. Five major regions of the genome were implicated in the control of infections caused by different Leishmania species which, because they show conserved synteny with regions of the human genome, immediately provides candidate gene regions for human disease susceptibility genes. A common intramacrophage niche for leishmanial and mycobacterial pathogens, and a similar spectrum of immune response and disease phenotypes, also led to the prediction that the same genes/candidate gene regions might be responsible for genetic susceptibility to mycobacterial infections such as leprosy and tuberculosis. Indeed, one of the murine genes (Nramp1) was identified for its role in controlling a range of intramacrophage pathogens including leishmania, salmonella and mycobacterium infections. In recent studies, multicase family data on visceral leishmaniasis and the mycobacterial diseases, tuberculosis and leprosy, have been collected from north-eastern Brazil and analysed to determine the role of these candidate genes/regions in determining disease susceptibility. Complex segregation analysis provides evidence for one or two major genes controlling susceptibility to tuberculosis in this population. Family-based linkage analyses (combined segregation and linkage analysis; sib-pair analysis), which have the power to detect linkage between marker loci in candidate gene regions and the putative disease susceptibility genes over 10-20 centimorgans, and transmission disequilibrium testing, which detects allelic associations over 1 centimorgan (ca. 1 megabase), have been used to examine the role of four regions in determining disease susceptibility and/or immune response phenotype. Our results demonstrate: (i) the major histocompatibility complex (MHC: H-2 in mouse, HLA in man: mouse chromosome 17/human 6p; candidates class II and class III including TNF alpha/beta genes) shows both linkage to, and allelic association with, leprosy per se, but is only weakly associated with visceral leishmaniasis and shows neither linkage to nor allelic association with tuberculosis; (ii) no evidence for linkage between NRAMP1, the positionally cloned candidate for the murine macrophage resistance gene Ity/Lsh/Bcg (mouse chromosome 1/human 2q35), and susceptibility to tuberculosis or visceral leishmaniasis could be demonstrated in this Brazilian population; (iii) the region of human chromosome 17q (candidates NOS2A, SCYA2-5) homologous with distal mouse chromosome 11, originally identified as carrying the Scl1 gene controlling healing versus nonhealing responses to Leishmania major, is linked to tuberculosis susceptibility; and (iv) the 'T helper 2' cytokine gene cluster (proximal murine chromosome 11/human 5q; candidates IL4, IL5, IL9, IRF1, CD14) controlling later phases of murine L. major infection, is not linked to human disease susceptibility for any of the three infections, but shows linkage to and highly significant allelic association with ability to mount an immune response to mycobacterial antigens. These studies demonstrate that the 'mouse-to-man' strategy, refined by our knowledge of the human immune response to infection, can lead to the identification of important candidate gene regions in man.
Animals↗
Cutaneous manifestations of immunogenetic deficiency disorders.
Explore the source record for details and available documents.
Adolescent↗
Immunogenetic study of three Japanese families with neonatal lupus erythematosus.
We encountered three Japanese families with neonatal lupus erythematosus. None of the three fathers showed any signs of collagen disease. The three mothers were found to suffer from Sjögren's syndrome; they all tested positive for anti-SSA and SSB antibodies and had lymphocyte infiltration into the small salivary gland. In two families, one child had neonatal lupus erythematosus while a sibling was normal; in the third family, both children had neonatal lupus erythematosus. Thus, a mother with positive anti-SSA and SSB antibodies can give birth to one infant with and one infant without or have two infants with neonatal lupus erythematosus. We conducted HLA typing of all 12 members of the three families in order to clarify the immunologic factors involved. We found no increased frequency of any HLA phenotype in the three mothers and their four children with neonatal lupus erythematosus; however, HLA-DR4 was present in three of the children with neonatal lupus erythematosus.
Adolescent↗
Immunogenetic polymorphism of lipoproteins in swine. 1. Four additional serum beta-lipoprotein allotypes (Lpp2, Lpp4, Lpp5 and Lpp15) in the Lpp system.
Four additional swine serum lipoprotein allotypes are described. Specific anti-allotype reagents were obtained from alloimmune precipitating sera produced in lipoprotein-defined-type recipients immunized with normal sera and subsequently with lipoprotein fractions. Identification studies indicate that the four serologically defined low-density lipoprotein (LDL) variants, designated Lpp2, Lpp4, Lpp5 and Lpp15, are members of a previously described Lpp system. The individual specificities, Lpp2, Lpp4 and Lpp5, are determined by three co-dominant autosomal genes, Lpp2, Lpp4 and Lpp5, respectively, whereas the common specificity, Lpp15, is controlled by a complex of genetic information of the Lpp2 and Lpp4 genes, and by the two previously described alleles, Lpp1 and Lpp3; Lpp15 occurs on the same molecule with respective individual specificity. The Lpp5 and Lpp15 antigens behave as a pair of alternative allotypic specificities. The double immunodiffusion test in agar was employed to demonstrate independent phenotypic expression of each allelic gene in the Lpp heterozygous animals, for the analysis of the immune sera, and for lipoprotein testing of 3305 sera. Marked differences in gene frequencies were found between the swine breeds tested. As a result of characteristic frequencies, only nine of 15 possible Lpp genotypes were found in the breeding herds tested; the remaining six genotypes were obtained from testcross matings.
Alleles↗
Immunogenetic studies of rhesus monkeys. 8. A new reagent of the G blood group system and an example of the founder principle.
A new reagent called G-3' has been discovered which detects the product of the G3 allele, regardless of the other G allele in the genotype. With this new reagent we can delineate nine of 10 genotypes of the G blood group system. The explicit detection of G3 revealed an example of the founder principle in that the frequency of this allele between the feral and laboratory-reared monkeys was significantly different.
Alleles↗
Immunogenetic studies of rhesus monkeys. 6. Absence of the human Xga blood group on rhesus erythrocytes.
It was not possible to demonstrate Xga on the erythrocytes of any of 140 rhesus monkeys of both sexes tested with human antiserum rendered specific for Xga by absorption.
Animals↗
Immunogenetic studies on wild pigs in Japan.
The variations of blood groups in the two subspecies of wild pigs in Japan (Sus scrofa leucomystax and S.s. riukiuanus) were investigated by serological techniques. S.s. leucomystax showed polymorphism in the A and F systems. S.s. riukiuanus showed a little polymorphism in the F system only. As a whole, there was a great similarity in erythrocyte antigen structures of both S.s. leucomystax and S.s. riukiuanus. In comparison with the erythrocyte antigen frequenties of wild pigs in the Eurasian Continent reported by other workers. East-West geographical clines in the frequencies of Ea, Fa, Ga, Ka, Kb and Lh antigens were clearly observed. From the results of investigation on genetic similarities among seven wild pig populations, it was made clear that the two Japanese strains were very close and were closer to Far Eastern TS.s. ussuricus) than Middle Asian (S.s. nigripes), Transcausian (S.s. attila) and European pigs (S.s. ferus).
Animals↗
Neonatal lupus erythematosus. Report of serological and immunogenetic studies in twins discordant for congenital heart block.
Autoantibody, HLA studies and C4 phenotypes were performed on twins discordant for isolated congenital heart block. Serum from the mother and cord blood from the infants revealed Ro(SSA) and La(SSB) antibodies in all three sera. No significant difference in Ro(SSA) antibody titre was noted in the cord blood of either twin when compared with maternal titres, as detected by a sensitive ELISA assay. The infants' mother was HLA-DR3 positive. Both infants had identical HLA and C4 phenotypes. Immunoblot analysis revealed that sera from both mother and infants reacted with the 52-kDa Ro(SSA) macromolecule. Quantitative cord blood IgM levels were not elevated in either twin. This study indicates that placental transfer of anti-Ro(SSA) or anti-La(SSB) alone to the fetus is not sufficient for the expression of congenital complete heart block. We conclude from this experiment of Nature that there must be a second event determining which infant develops complete heart block, but this is unknown at present.
Adult↗