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At least 199 records · Page 11Linked to original sources
PubMed1982

Seronegative rheumatoid arthritis. A distinct immunogenetic disease?

Measurement of serum rheumatoid factor (RF) by conventional methods in patients with rheumatoid arthritis (RA) has repeatedly identified a subpopulation of patients without detectable RF. Previous investigators have consistently confirmed the association of HLA-DR4 with seropositive RA, but studies of seronegative RA have been limited and contradictory. We studied 140 randomly selected patients from Alabama, all of whom had either classic or definite RA, and we were able to complete HLA typing for 110 of these individuals. Eighty were consistently seropositive (on at least 2 separate occasions) and 30 were consistently seronegative (on at least 3 separate determinations). There was no statistically significant difference between the seronegative RA patients and 123 control subjects in the distribution of DR antigens. In seropositive RA, there was a significant increase in DR4 (P less than 0.001; relative risk = 8.02; attributable risk = 49.2%) and a significant decrease in DR3 (P less than 0.001; relative risk = 0.14) and DR7 (0.01 greater than P greater than 0.001; relative risk = 0.33). The clinical data also distinguished between seropositive RA and seronegative RA; subcutaneous nodules (37.5%) and vasculitis (6.3%) were present only in seropositive RA. DR4 positively did not correlate with any of the clinical variables measured in the seropositive RA group. In contrast, DR4 in the seronegative RA group was associated with more destructive disease. The data suggest that seronegative RA represents a disease entity clinically and immunogenetically distinct from seropositive RA. Moreover, our results indicate that DR4 may be a previously undisclosed marker for disease severity in seronegative RA.

Arthritis, Rheumatoid↗
PubMed1993

Autoantigenic epitopes on DNA topoisomerase I. Clinical and immunogenetic associations in systemic sclerosis.

OBJECTIVE: To elucidate the clinical and immunogenetic associations with reactivity to autoantigenic epitopes on DNA topoisomerase I (topo I) recognized by sera from patients with systemic sclerosis (SSc). METHODS: Autoantigenic epitopes on topo I were identified by screening an epitope library constructed from topo I complementary DNA restriction fragments using autoimmune anti-topo I-positive sera as a probe. Epitope reactivities of sera from 43 anti-topo I-positive SSc patients were surveyed by immunoblotting, and associations with clinical symptoms and HLA-DR types were examined. RESULTS: Four different epitope regions were identified on the topo I molecule. Immunoreactivity to the region encompassing amino acid residues 658-700, termed ER4, was found to be associated with diffuse cutaneous SSc, progressive pulmonary interstitial fibrosis, and poor prognosis for 15-year survival. SSc patients with ER4 reactivity frequently displayed the DR2/DRw52 phenotype. CONCLUSION: Molecular analysis of precise antigenic epitopes on topo I is helpful in classifying clinical subsets of SSc.

Adult↗
PubMedDate not supplied

Immunogenetic studies of autoimmune chronic active hepatitis: HLA, immunoglobulin allotypes and autoantibodies.

The strategy of assigning a surrogate phenotype, defined as the presence of antinuclear and/or antismooth muscle antibodies to disease-free first degree relatives of index cases was used to search for a postulated disease susceptibility gene in autoimmune chronic active hepatitis. In addition to determining circulating autoantibody status, 10 patients, 51 first-degree relatives and 6 spouses of index chronic active hepatitis patients, each ascertained by the single patient, were genotyped for HLA (A, B and DR loci) and immunoglobulin allotype (G1m, G2m, G3m and A2m loci) haplotypes. Among the 10 chronic active hepatitis patients, 6 had HLA haplotypes B8 and DR3, and 3 of these patients had, in addition, the immunoglobulin allotype haplotype Gm a,x;g. Circulating autoantibodies defining the surrogate phenotype was found in 39% of the first-degree relatives. However, segregation analysis offered no support for either single autosomal dominant or recessive inheritance for the autoantibody-positive phenotype. Linkage between the postulated disease susceptibility locus and either the HLA (Chromosome 6) or immunoglobulin (Chromosome 14) locus was excluded by several analyses. Furthermore, logistic regression indicated that neither immunogenetic marker was statistically associated with autoantibody positively in these families. Therefore, despite the occurrence of autoantibody positivity in first-degree relatives of autoimmune chronic active hepatitis patients, we found no evidence that this trait has a simple genetic basis, or that it is an alternative manifestation of a postulated disease susceptibility gene for chronic active hepatitis.

Antibodies, Antinuclear↗
PubMed1987

Immunogenetic studies of maternal-fetal relationships: a review: why newborn rhesus monkeys don't get hemolytic disease.

The discovery of the Rh blood group factor in humans was made using the red blood cells of rhesus monkeys. Because of its importance to human medicine and immunogenetics, this finding contributed greatly to the appreciation of the importance of nonhuman primates in research. It is now widely recognized that blood group incompatibility between mother and fetus can lead to differential fertility, fetal death, and hemolytic disease of the newborn (HDN). The blood group systems of several nonhuman primate species have been studied in detail and found to be analogous, although not identical, to those of humans. It is therefore surprising that HDN has been reported in only four nonhuman primate species--marmosets, sacred baboons, chimpanzees, and orangutans. Maternal-fetal blood group incompatibility and its consequences have been extensively studied in rhesus monkeys, and these macaques may well be representative of many nonhuman primates. Rhesus monkeys exhibit all five of the conditions that lead to HDN in humans: (1) blood group incompatible matings; (2) transplacental hemorrhage; (3) maternal immunization to blood group alloantigens on fetal erythrocytes; (4) transplacental transfer of maternal antibodies; and (5) coating of the newborn's erythrocytes. Yet, newborns show no clinical or hematological evidence of HDN. We have shown that the rhesus alloantibodies engendered by transplacental immunization do not mediate immune elimination of the newborn's erythrocytes. Evaluation of the maternal antibodies demonstrated that they have low titers and low avidities and perhaps belong to IgG subclasses that do not bind effectively to receptors on phagocytic cells of the rhesus reticuloendothelial system. The newborn's genotype may also affect the expression of allogeneic blood group antigens and thereby help protect the newborn's cells from destruction. These factors together undoubtedly play a major role in the survival of the antibody-coated newborn's RBC and are thus able to account for the absence of HDN in this species.

Animals↗
PubMed1989

Immunogenetic heterogeneity in type 1 (insulin-dependent) diabetes among Japanese HLA antigens and organ-specific autoantibodies.

HLA phenotypes and haplotypes in relation to organ-specific autoantibody responses were studied in 82 Japanese patients with Type 1 (insulin-dependent) diabetes. HLA-DRw9 antigen and HLA phenotype of DRw9/X (X:not DR4) were increased in patients with organ-specific autoantibodies other than islet cell antibody (CP less than 0.02, RR = 4.02 and p less than 0.05 RR = 2.30, respectively); whereas HLA-DR4 antigen and HLA phenotype of DR4/X (X: not DRw9) were increased in those without the autoantibodies (CP less than 0.001, RR = 3.95 and p less than 0.01, RR = 2.46, respectively). HLA haplotype of Bw61-DRw9 was increased in patients with the autoantibodies (p less than 0.005, RR = 4.94), and HLA haplotype of Bw54-DR4 was increased in those without the autoantibodies (p less than 0.001, RR = 5.52). The relative risk of HLA-DR4/DRw9 was the highest among all HLA-DR phenotypes or genotypes in patients either with or without the autoantibodies. No association was, however, found between the incidence of islet cell antibody and HLA-DR phenotypes. These findings suggest that Type 1 diabetes among Japanese is immunogenetically heterogeneous as is Type 1 diabetes among Caucasians; and the differences in HLA-association of Type 1 diabetes among ethnic groups might give a clue to understanding of a role of HLA-antigens in the development of Type 1 diabetes.

Autoantibodies↗
PubMed1978

Immunogenetic study on the polymorphism of serum alpha2-lipoproteins in mink. II. Identification of allotypes Lpm-7 and Lpm-8 and genetic control of seven markers of the Lpm system.

By means of alloimmunization of mink, two new antigens, Lpm-7 and Lpm-8, were detected in their sera. Lpm-7 and Lpm-8 allospecificities were referred to a very high density alpha2-lipoprotein (Lpm) by the following criteria: histochemical tests, immunoelectrophoresis, preparative ultracentrifugation, and coalescence of alloprecipitates with heteroprecipitates in double diffusion tests. Genetic analysis indicated that Lpm-7 and Lpm-8, together with the earlier described Lpm-1, Lpm-2, Lpm-3, Lpm-4, and Lpm-5, share a common immunogenetic system. Polymorphism for the seven markers is conditioned by the genetic units Lpm8, Lpm4, Lpm4,8, Lpm4,7, Lpm3,4,8, Lpm1,8, Lpm1,2,7, and Lpm2,4,5,7, which behave as alleles. Of these units, the latter six are probably haploid sets of closely linked genes.

Alleles↗
PubMedDate not supplied

Immunologic and immunogenetic studies in rheumatic fever and rheumatic heart disease.

In order to evaluate all the important limbs of the immune system in the same patient population with rheumatic fever (RF) and rheumatic heart disease (RHD) cellular and humoral immune parameters as well as the immunogenetic profile in 265 North Indian patients with RHD were evaluated. They were studied for class in HLA antigens and 165 of them were also evaluated for the class II (DR locus) antigen profile. Data obtained was compared with 400 and 134 healthy controls respectively of the same ethnicity. Humoral immune parameters (Serum immunoglobulins IgG, IgA; Serum complement fractions C3, C4, C3d; circulating immune complexes and B lymphocyte numbers) and cellular immune parameters (total leucocyte and lymphocyte counts; T lymphocyte sub-populations--CD4, CD8 counts; lymphocyte migration inhibition to an extracellular streptococcal antigen, streptolysin 'O') were studied in 23 patients with RF, 21 patients with "inactive" RHD and 20 normal controls. Patients of RHD were noted to have an increased frequency of DR3 (P less than 0.001; Relative risk = 2.3) and a decreased frequency of DR2 (P less than 0.001; Relative risk = 0.3) as compared to the controls. Patients of RF had evidence of an altered regulatory T cell function (increased CD4/CD8 ratio) and decreased cell mediated immunity to streptolysin 'O'. An increased humoral immune response (increased B cell counts, elevated serum IgG, circulating immune complexes and C3d) was noted in patients of RF as well as "inactive" RHD. An integrated pathogenetic model with immune response associated antigens of the DR locus influencing selection of cardiac cross-reactive antigens by the antigen processing macrophages, an altered regulatory T cell function with decreased suppressor T cell activity leading to an abnormal immune response is proposed to explain the pathogenesis of RF.

HLA Antigens↗
PubMed1993

Comparison of the clinical and immunogenetic features between patients with autoimmune hepatitis and patients with type C chronic active hepatitis.

We clarified the clinical and immunogenetical differences between patients with autoimmune hepatitis (AI-CAH), and patients with type C chronic active hepatitis (C-CAH) and type B chronic active hepatitis (B-CAH) who were positive for autoantibodies and hyperglobulinemia. While histories of blood transfusion, intravenous drug abuse and tattoo were seen frequently in patients with type C-CAH, they were rare in patients with AI-CAH. The severe subjective symptoms including anorexia, lethargy, icterus, high fever and extrahepatic manifestations, and severe abnormality of biochemical data were seen in AI-CAH predominantly. Ongoing or past infection of HCV was seen in only 14% of patients with AI-CAH. HLA-DR4 was the most frequently associated with AI-CAH (89%) and 6 DR4-negative patients were positive for DR2. HLA-DNA typing showed that there was no significant difference in the frequency of DR4-associated Dw-alleles between the patients and controls who were positive for DR4. These findings suggest that the basic amino acid at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg on DR2 and His on DR4), may contribute to the susceptibility to autoimmune hepatitis of Japanese. Thus, we conclude that AI-CAH is a genetically restricted, disease, and different from C-CAH which is a viral infectious disease.

Adult↗
PubMed2005

An immunogenetic basis for the high prevalence of urogenital cancer in a free-ranging population of California sea lions (Zalophus californianus).

In response to an unprecedented prevalence of cancer recently identified in free-ranging populations of California sea lions [(CSL) (Zalophus californianus], we examined the role of the immunologically important major histocompatibility (MHC) genes in this disease epidemic. Associations between MHC genes and cancer have been well established in humans, but have never before been investigated in wildlife. Using a previously developed technique employing sequence-specific primer-based PCR with intercalating dye technology, MHC genotypes were examined from 27 cancer-positive and 22 cancer-negative CSL stranded along the California coastline. Analyses elucidated an underlying immunogenetic component to the high prevalence of urogenital cancer in sea lions. Furthermore, these results demonstrate the functional relevance of CSL class II MHC by revealing a non-random nature of cancer susceptibility associated with the presence of specific genes.

Animals↗
PubMed2003

RS3PE syndrome: a clinical and immunogenetical study.

This study analyses the clinical, radiological, evolutive, and immunogenetical characteristics of a series of patients diagnosed with remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. Reviewed were the clinical charts and human leukocyte antigen (HLA) profiles of all patients treated at a single teaching hospital fulfilling the features of this syndrome according to the definition of McCarty. Twelve cases were detected in ten men and two women aged from 62 to 85 years. Rheumatoid factor was negative in all cases, and antinuclear antibodies (ANA) were positive in two. All patients achieved complete resolution of their condition within 1 year with glucocorticoid (GC) use. Two relapsed after remission but responded again to low doses of GC. Four patients showed clinical and electrodiagnostic studies consistent with carpal tunnel syndrome. No specific HLA association could be found in this report. To date, none of these patients has developed definite rheumatic diseases, infections, or malignant diseases. Although the real nature of the syndrome is still a matter of debate, at least in our context, RS3PE remains a definite condition with an excellent prognosis.

Aged↗
PubMed1987

Immunogenetic factors involved in the pathogenesis of distinct clinical manifestations of schistosomiasis japonica in the Philippine population.

Immunogenetic factors were studied in 60 patients with schistosomiasis japonica in the Philippines, of whom 15 were characterized by marked hepatosplenic lesions and 45 characterized by cerebral symptoms. Immune responsiveness of the patients to schistosomal antigen was measured by T cell proliferation in vitro, and their HLA-A and -B specificities were typed. All but one hepatosplenic patients showed strong immune responsiveness to the schistosomal antigen, whereas both low and high responders were observed in the cerebral patients. A significant association between HLA-B40 and high responders to the schistosomal antigen was observed (P = 0.0458), and this HLA specificity was increased in frequency in the hepatosplenic patients. HLA-B16 was not observed in the hepatosplenic patients, but was common in the cerebral patients (26.5%) (P = 0.0255), and this HLA specificity was commoner in the low responders than in the high responders. These observations suggest that an HLA-linked gene governs the clinical manifestations of human schistosomiasis japonica by controlling immune responsiveness of the infected hosts to the schistosomal antigen.

Adolescent↗
PubMed1990

Genotype and phenotype: a practical approach to the immunogenetic analysis of lymphoproliferative disorders.

Determination of cell lineage and clonality in lymphoproliferative disorders (LPD) is greatly enhanced by molecular genetic analysis in conjunction with morphologic and immunologic techniques. We now report on a technique in which we used cryostat-cut, fresh-frozen sections (CCFFS) prepared from tissues in a manner that allows DNA hybridization studies to be coordinated readily with routine morphologic and immunohistologic studies. Thirty-seven cases representing a broad spectrum of reactive and malignant LPD were examined with this method. Samples of DNA were extracted from frozen sections, subjected to Southern blot hybridization, and probed for rearrangements of the immunoglobulin (Ig) heavy-chain and the kappa and lambda light-chain genes, as well as for the T-cell receptor beta-chain gene. We also evaluated the effects of (1) diagnostic category of LPD, (2) volume of the tissue sample, and (3) fibrosis, necrosis, and ice crystal artifacts in the sample on the recovery of DNA. Ice artifact and sample size had the greatest negative impacts on the quantity and condition of DNA recovered. Of 19 samples involved by B-cell LPD, the results of immunogenetic studies were consistent with the immunophenotypes in all but one case. Of the T-cell lymphomas from which sufficient DNA was available (three out of five of the T-cell cases), all showed rearrangements of the T-cell beta-chain gene. In order to reduce sample processing time, we evaluated alternate blot hybridization methods, rapid alkaline transfers, and direct hybridization of synthetic oligonucleotides in dried agarose gels, and found that they decreased the time required for hybridization studies. In summary, the use of CCFFS as the source of DNA allows study of gene rearrangements and, at the same time, preserves frozen-tissue blocks in tumor banks for further immunologic studies. The development of time-effective methods will make the routine use of molecular-genetic analysis more practical in the diagnostic hematopathology laboratory.

Culture Techniques↗
PubMedDate not supplied

Immunogenetic and evolutionary influences on the host-parasite relationship.

Immunogenetic aspects of the host-parasite relationship between the laboratory mouse and the parasitic nematode Trichinella spiralis are reviewed. Variation in the capacity of hosts to express an effective protective immunity is associated primarily with variation in inflammatory responsiveness. Analysis of the contributions of T lymphocytes, cytokines, and myeloid precursor populations to variation in one particular inflammatory component, eosinophilia, is described. Variation in parasite immunogenicity at the level of host responsiveness to different parasite isolates is described briefly. Variations in host-protective immunity, immunopathology, and parasite immunogenicity are discussed in terms of evolutionary pressures selecting for optimal host and parasite survival in a stable symbiosis.

Animals↗
PubMed1983

Immunogenetic analysis of the HLA complex with alloreactive T cell clones.

Recently developed technologies to clone alloreactive human lymphocytes have provided a powerful tool for the immunogenetic analysis of the HLA region. Alloreactive T cell clones can be used as specific reagents for HLA encoded cellular determinants detected in secondary proliferation assays such as the primed lymphocyte test (PLT) and, in cell-mediated lympholysis (CML). Lymphocyte clones can also be used for functional assays (e.g., for suppressor or helper activity) to determine the influence of HLA specific restriction.

Clone Cells↗
PubMed2004

Type 1 diabetes in Jewish Ethiopian immigrants in Israel: HLA class II immunogenetics and contribution of new environment.

The interrelationship between human leukocyte antigen immunogenetics and environmental factors and their contribution to the emergence of type 1 diabetes (T1D) were studied in Jewish immigrants from Ethiopia in Israel. This community displays high incidence of T1D, and is unique both by its ethnic segregation and its rapid exposure to a new environment after the immigration. The study population consisted of 152 Ethiopian Jews living in Israel, 33 with T1D and 119 unrelated controls. Human leukocyte antigen class II susceptible and protective alleles in the Jewish Ethiopian patients were similar to those in patients of other ethnic groups in Israel and in non-Jewish Ethiopian patients, with a few exceptions. Three haplotypes were markedly associated with diabetes in Jewish Ethiopian patients: DRB1*0301 DQA1*05 DQB1*02 (OR 4.4, p < 0.001); DRB1*0404 DQA1 03 DQB1*0302 (OR 19.2, p = 0.006), and DRB1*0405 DQA1*03 DQB1*0302 (OR 87.8, p < 0.001). The highly susceptible allele DRB1*0301 was more common in the general Ethiopian population (25.2%) than in all other ethnic groups in Israel, which may render this community prone to the disease. The age at onset of disease in patients with two susceptible haplotypes was negatively correlated with the duration of living in Israel (r = -0.621, p = 0.04). We concluded that ongoing exposure of genetically predisposed immigrants from Ethiopia to diabetogenic environmental factors eventually leads to a high incidence of overt diabetes in this ethnic group.

Adolescent↗
PubMed2006

[The immunogenetics of ankylosing spondylitis].

BACKGROUND: Ankylosing spondylitis (AS) is an inflammatory rheumatic disease with axial involvement but its physiopathology remains unexplained. This latter combines genetic and environmental factors as well as an abnormal immune response. CURRENT TOPICS AND IMPORTANT RESULT: This review addresses the different aspects of AS immunogenetic. A genetic background in AS is suggested by familial cases, concordance rate in twins and transmission of the disease in siblings. Ankylosing spondylitis is strongly associated with the expression of the HLA Class I antigen, B27, but also with other genes not yet identified since currently, only chromosomic area have been linked to AS. Studies of candidate genes or genome screening allow to determine these chromosomic regions. HLA-B27 is directly associated with the disease physiopathology as suggested by animal models of rats transgenic for human HLA-B27 and beta2 microglobulin. This HLA molecule have original biological properties, in particular a slow heavy chain folding and the formation of heavy chain homodimers without light chain. However, HLA B27 is a functional molecule and assumes its property of presenting peptide of 9 amino acids to CD8+ T cells. Interaction modelling studies between HLA B27 and peptides have identified peptide and peptide groove amino acid sequences, with the identification of critical positions on the HLA B27 molecule for the peptide interaction. Original biochemical properties of HLA-B27 include diminished bacterial antigen response and CD4+ T lymphocyte stimulation. Innate immunity is also of interest in AS, as suggested by the presence of macrophage and polymorphonuclear neutrophils in AS synovitis, as well as the contribution of Toll-like receptors. FUTURE PROSPECTS AND PROJECTS: Thus in AS, the inflammatory process and then the clinical consequences may be explained by the involvement of HLA-B27, a bacterial antigen presentation, an abnormal immune response and the contribution of innate immunity, T CD4+ but also T CD8+ cells. The original molecular structures of HLA-B27 are certainly involved in this complex physiopathology, but their direct influence on the disease remains to be precised.

Animals↗
PubMed2006

Is MHC enough for understanding wildlife immunogenetics?

Along with reproductive success and predation, infectious disease is a major demographic and evolutionary driver of natural populations. To understand the evolutionary impacts of disease, research has focussed on the major histocompatibility complex (MHC), a genetic region involved in antigen presentation. There is a pressing need for the broader research currently conducted on traditional vertebrate models to be transferred to wildlife. Incorporating such knowledge will enable a broader understanding of the levels at which natural selection can act on immunity. We propose two new approaches to wildlife immunogenetics and discuss the challenges of conducting such studies. At a time when novel pathogens are increasingly emerging in natural populations, these new approaches are integral to understanding disease dynamics and assessing epidemic risks.

Animals↗
PubMed1997

Recognition of an immunogenetically selected Trypanosoma cruzi antigen by seropositive chagasic human sera.

If the H-2 congenic mouse strains A.SW (H-2n) and A.CA (H-2f), are infected with Trypanosoma cruzi, a 45 kDa protein (Tc45), present in cultured epimastigotes and blood trypomastigotes, is recognized only by the A.SW strain sera. In order to explore the possibility that among seropositive humans the response to Tc45 is also highly variable, 81 chagasic human sera (as defined by the HemAve agglutination test, Polychaco S.A.I.C., Buenos Aires, Argentina) were tested in a direct (epimastigote antigenic complex directly bound to the solid phase) and indirect immunoradiometric assay (IRMA) (Tc45, from a partially purified preparation, bound to the solid phase, by means of a monoclonal antibody). Sixty nine of these sera reacted in both the direct and indirect assays, 11 were negative in both assays (these samples may correspond to false positives detected by the commercial agglutination test) and only one reacted with the antigenic complex but not with Tc45. Reactivity of the human sera with the epimastigote antigenic extract was relatively homogenous, while reactivity with Tc45 was extremely variable. No statistical correlation was determined between the two variables. Given the high variability of the human response to Tc45, ranging from negative to highly positive, together with the immunogenetic restriction previously described in the murine model, we speculate that human MHC may also modulate the response to this molecule.

Agglutination Tests↗