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Biomedical subjects

C Darke

Publications and source records attributed to C Darke.

At least 109 records · Page 6Linked to original sources
PubMed1989

HLA class I (Bg) antigens on red cells of SLE patients: a serological study with polyclonal and monoclonal antibodies.

The enhanced HLA class I (Bg) on red blood cells (RBC) of many patients with systemic lupus erythematosus has allowed a significant correlation to be made between their HLA-B types and haemagglutination reactivity with lymphocytotoxic anti-HLA-B sera stimulated by pregnancy alone. Therefore the class I expression on these RBC relates to classical, rather than non-classical, class I gene products. Studies of class I expression on RBC by means of monoclonal antibodies (MAb) to epitopes on the heavy polypeptide chain and beta 2-microglobulin (beta 2m) have suggested that the complete extracellular structure is present. The specific effect of chloroquine in 'stripping HLA' from RBC had been assumed to support the concept that HLA class I was adsorbed from plasma. However, from our data, we conclude that HLA class I is an intrinsic membrane component. We suggest that the action of chloroquine is to remove beta 2m alone, which prevents normal class I expression and also results in conformational changes to the class I heavy chain, but that it is not capable of removing the membrane-bound heavy chain.

Antibodies↗
PubMed1989

A comparison of DNA-RFLP typing with serology and mixed lymphocyte reaction in the selection of matched unrelated bone marrow donors.

Eleven leukaemic patients and 43 potential unrelated marrow donors were typed serologically, tested in mixed lymphocyte reaction (MLR) and typed by restriction fragment length polymorphism (RFLP) analysis. RFLP typing data were compared with DR serology and MLR results. Eleven of the 54 individuals showed discrepancies between DR serology and RFLP DR assignment. RFLP DR/DQ mismatch always correlated with positive MLR, but RFLP identity was present in both MLR negative and MLR positive pairs. RFLP typing cannot reliably predict a negative MLR response, but we suggest that it should be used in the selection of unrelated marrow donors to exclude mismatched donors from testing in the MLR. This will facilitate donor searches by reducing the number of MLR performed.

Bone Marrow Transplantation↗
PubMed1988

HLA class I and H ferritin gene polymorphisms in normal subjects and patients with haemochromatosis.

The gene for idiopathic haemochromatosis is located on the short arm of chromosome 6 within 1 cM of the HLA-A locus. In this region there are many HLA class I genes, and there may also be a gene for the 'H' subunit of ferritin. Both HLA class I and H ferritin genes are therefore candidates for the abnormal gene in idiopathic haemochromatosis. In 15 unrelated patients the frequency of HLA-A3 was 80% compared with 24% for 600 unrelated individuals from South Wales. The most common haplotype involved is probably HLA-A3, B7. DNA was prepared from leucocytes from 12 of these patients and from 85 normal subjects. After digestion with Taq1, electrophoresis, and Southern blotting, class I sequences were detected by hybridisation to an HLA class I probe (pHLA-A). Of the 34 restriction fragments detected, 22 were polymorphic. Particular fragments correlated with the presence of HLA-A antigens A1, 2, 3, 10, 11, w19, and 28, but there was little correlation with B antigens. Restriction fragment patterns specific for haemochromatosis were not found with TaqI or during less extensive studies with other restriction enzymes. No differences in restriction fragment patterns were found between four patients and four normal subjects apparently homozygous for HLA-A3 and B7. Examination of Southern blotting patterns for genomic DNA from patients and normal subjects with a panel of 12 restriction enzymes and a probe for the H ferritin gene (pDBR-2) revealed no polymorphisms associated with either idiopathic haemochromatosis or particular HLA phenotypes. These studies provide no support for either HLA class I genes or the H ferritin gene as candidates for the haemochromatosis gene.

DNA Restriction Enzymes↗
PubMed1988

Association between HLA antigens and periodontal disease.

HLA-A, B and DR antigen frequencies were determined in three groups of periodontally diagnosed subjects: 49 patients with rapidly progressive periodontitis, 40 elderly subjects with minimal disease (considered as a resistant group) and 30 young subjects with minimal disease. The relative risk for HLA-A9 (previously reported to be associated with periodontal disease) was 15.5. HLA-A9 was present in 36.7% of the patients and 2.5% of the resistant group. HLA-A10 showed a significantly increased incidence in the resistant group (30.0%) compared to a non-periodontally diagnosed control population (9.0%), and was absent from the patient group. These findings provide additional evidence for the involvement of HLA-A9 in susceptibility to periodontitis, and suggest that A10 may play a role in resistance to the disease.

Adult↗
PubMed1987

Association of HLA-Bw65 with two major complotypes.

The association between the HLA-B14 subtypes Bw64 and Bw65 and complement allotypes (C2, Bf and C4) was investigated in both population and family studies. Bf, C4A and C4B allotyping was performed on 37 Bw64 and 35 Bw65 positive unrelated Welsh/English subjects. Sixteen HLA-Bw65 bearing haplotypes were characterized for HLA-ABC, DR and DQ antigens and complement allotypes, including C2. The findings of the population study suggested that the complement haplotype associated with Bw64 is BfS, C4A2, C4B2. The population and family studies revealed two major complement haplotypes associated with HLA-Bw65: (i) C2C, BfF, C4A3, C4A1 - often associated with HLA-A3, Cw8 and DRw13, and (ii) C2C, BfS, C4A2, C4B2 - often associated with HLA-Aw33, Cw8 and DR1 or with A28, Cw8 and DRw13. The HLA-Bw65 bearing haplotypes of three families carried a C4B2B1 duplication of the C4B locus. In these families three C4B gene products were identified in the Bw65 positive members using an anti-C4B monoclonal antibody. It is suggested that most, if not all, HLA-Bw65 bearing haplotypes may possess a C4B locus duplication.

Antibodies, Monoclonal↗
PubMed1987

Production of an HLA-DRw13 antibody in a DRw14 positive multiparous woman.

A lymphocytotoxic HLA-DR alloantiserum (Ma159) which reacts with DR7, DR5 and DRw13 positive lymphocytes is described. It was non-cytotoxic against 27 DRw14 positive subjects and was not absorbed by DRw14 positive cells. The antiserum was produced by pregnancy alone in a DR4, DRw14 positive woman whose husband possesses DR7 and DRw13. Absorption and titration studies suggested that the antiserum contains separate antibodies directed towards DR7, DRw13 and a determinant shared by DR5 and DRw13. The implications of finding a specific anti-DRw13 antiserum and its production in a donor positive for the alternative subdivision of DRw6 are discussed.

Antibody Specificity↗
PubMed1987

HLA and multiple sclerosis in south east Wales.

A stronger association has been found between multiple sclerosis and HLA-DR2 than -DQwl in south east Wales (prevalence c 113/10(5)) in contrast to recent observations in north east Scotland (prevalence 178/10(5). The complex relationship between the HLA system and multiple sclerosis, demonstrated in this and other studies, is explained more easily under a polygenic model of inheritance, in which environmental events and genes interact, than by the presence of a single susceptibility gene.

Gene Frequency↗
PubMed1987

Expression of MHC class I determinants on erythrocytes of SLE patients.

Strong expression of MHC Class I determinants had been observed on the erythrocytes of three genetically C4 deficient patients who all had SLE. In a study of 35 other SLE patients who were not C4 deficient, 30 showed a marked increase in the expression of MHC Class I on their erythrocytes. There was a correlation between the expression of erythrocyte Class I and disease activity. The polymorphic HLA determinants were detected by haemagglutination with human cytotoxic antisera from untransfused pregnant women. A shared monomorphic epitope of HLA-A, -B and -C, and beta 2-microglobulin were detected by haemagglutination with monoclonal antibodies. A monoclonal antibody for a monomorphic epitope on MHC Class II alpha and beta chains did not react. Erythrocytes from a group of RA patients and a group of normal controls had moderate and low expression respectively. We suggest that MHC Class I may be induced on erythrocytes maturing in a milieu containing mediators derived from activated cells of the immune system. Aberrant tissue expression of MHC antigens may be more widespread than has been previously recognized in diseases mediated by immune mechanisms.

Arthritis, Rheumatoid↗
PubMed1987

Cellular immunity to collagen in periodontal disease: role of T, B lymphocytes and adherent cells.

Peripheral blood lymphocytes of patients with periodontal disease and control subjects were fractionated into T enriched and B enriched lymphocyte populations and plastic adherent cells (PACs). T enriched and B enriched lymphocytes were cultured: (a) with human Type I collagen with varying concentrations of PACs and (b) without collagen, but with cells or supernatants from autologous and heterologous PACs which had been previously cultured with and without collagen. In patients with periodontal disease, both T enriched and B enriched blastogenic responses were higher than in control subjects, but B enriched cell responses of patients were highest. The addition of PACs had no significant effect upon the enriched T cell responses to collagen; the B enriched cell responses were enhanced in the presence of PACs, the maximum response occurring with the addition of approximately 10% PACs. T enriched cells did not appear to respond to the collagen co-cultured PACs or PAC supernatants; B enriched cells responded maximally to PACs co-cultured with collagen. Autologous PACs, co-cultured with collagen, induced higher responses than heterologous PACs similarly treated.

Adult↗
PubMed1986

Prediction of outcome in Graves' disease after carbimazole treatment.

In a prospective study to determine which factors would predict remission or relapse, 65 patients with hyperthyroid Graves' disease were treated for six months with a blocking replacement regimen of carbimazole, 40 mg daily, and triiodothyronine (T3). They were followed for one year after stopping treatment, by which time 32 (49 per cent) had relapsed. Although the treatment protocol, relapse rate and frequency of the HLA-DR3 antigen in this population were similar to those of a regionally separate Graves' population investigated previously, the predictive value of HLA-DR3 status together with thyroid stimulating antibody (TSAB) levels was strikingly different. In the present study there was no significantly abnormal distribution of any HLA antigen in the relapse group compared with those patients who achieved remission. Thyroid stimulating antibodies were detected in 62 patients (95 per cent) and fell significantly (p less than 0.05) after carbimazole treatment, irrespective of DR3 status or outcome; TSAB levels only became undetectable in nine patients (28 per cent) who subsequently relapsed and in nine patients (30 per cent) who maintained remission. T3-suppressed 20 min 123I uptake fell equally after treatment in the relapse and remission groups but continued to fall thereafter in the group which maintained remission. In these patients, 123I uptake was significantly lower at the end of the study period than at the end of treatment (p less than 0.05). Serum free T4 levels were higher before treatment in the patients who later relapsed than in those whose disease remitted (p less than 0.02). This proved the only significant marker associated with outcome but was of little predictive value in any patient. This study highlights the problem in predicting the outcome of antithyroid drug treatment, since even within the same country under similar conditions, divergent results have been obtained. It appears that the loci controlling the immune response in Graves' disease are likely to include genes lying outside the HLA-DR region. The results also suggest that the immunological effects of antithyroid drugs are maintained after stopping treatment in those patients whose disease remits.

Adult↗
PubMed1985

A F(ab')2 fragment blocking study of the HLA-B14 antigen.

The HLA-B14 antigen exists in two serologically distinct forms termed Bw64 and Bw65. These two B14 subgroups were studied using the ability of F(ab')2 fragments from HLA-B14 and Bw6 antisera to block the binding of cytotoxic HLA antibodies directed towards the same or an adjacent antigenic site. The findings suggest that the B14 antigen consists of several antigenic determinants some of which are spatially distinct and others which are closely associated. A "common" determinant possessed by both B14 subtypes is proposed which is separate from a Bw64 (or Bw65) site. Additional determinants that B14 shares with B8, B18 and B38/B39 appear to be distinct from the Bw64/Bw65 site, variably associated with the B14 "common" determinant but closely adjoining the Bw6 antigen.

Binding, Competitive↗
PubMed1984

Linkage disequilibrium between the HLA-B14 subdivisions and HLA-A, DR and properdin factor B alleles.

The recently reported linkage disequilibrium between HLA-B14.1 and DR7 and B14.2 and DR1 has been confirmed in a study of 44 B14.1 and 40 B14.2 positive individuals. In addition, significant linkage disequilibrium was observed between BfF and B14.2. Data on 238 B14 positives (98 B14.1 and 140 B14.2), from a population of 4,238, continues to support the previous observation of associations between B14.1 and Aw32 and B14.2 and A3, A28 and Aw33. These findings add further evidence for the existence of B14 splits.

Alleles↗
PubMed1984

A serological study of the HLA-B17 cross-reactive group.

The HLA-B17 cross-reactive group and the participation of the subdivisions of B17 ( Bw57 and Bw58 ) in cross-reactivity were investigated by the serological analysis of 81 cytotoxic HLA antisera (produced by pregnancy alone), the HLA typing of the antiserum donors and the identification of their immunizing antigens. The sera, all of which contained B17 activity, were produced in response to one of 10 HLA antigens (A2, Bw44, Bw49, Bw51, Bw55 , Bw56 , Bw57 , Bw58 , Bw62 and Bw63 ). Antisera stimulated by Bw57 and Bw58 cross-reacted with Bw49 and both subdivisions of B5 and B15, with bidirectional cross-reactivity occurring in many instances. Bidirectional cross-reactivity was also observed between Bw57 and A2 (an A2 stimulated antiserum also reacted with Bw58 ), and Bw57 and Bw55 . Immunization by Bw62 produced some antisera which showed strong cross-reactivity with Bw57 but no reactivity with Bw58 . Significant HLA-B antigen frequency disturbances were found in the responders to the B17 cross-reactive group antigens. Twenty-five HLA antigens were found to comprise the B17 cross-reactive group and its related cross-reactions. The multideterminant nature of the HLA antigens is again emphasized by these findings.

Cross Reactions↗
PubMed1983

The HLA-B12 and -B40 cross-reactive groups and their serological relationships.

The serological analysis of 82 broad HLA-B antisera, produced by pregnancy alone, containing reactivity against HLA-B12 and/or B40 positive cells and up to nine additional specificities was performed, using highly selected lymphocyte panels. The HLA typing of 76 of the antiserum donors and 75 of their husbands showed that the antisera were stimulated in response to one of 10 different HLA-B antigens. It also showed the influence of serum donor HLA-B antigens on the reaction range of the antiserum produced, as well as significant HLA-B antigen frequency disturbances within various groups of the antiserum donors. Fifteen HLA-B specificities were found to comprise the B12 cross-reactive group and its related cross-reactions, with bidirectional cross-reactivity occurring between Bw44, Bw45, Bw49 and Bw50 (unidirectional between Bw44 and Bw50). Seventeen specificities were observed in the B40 cross-reactive group and its related cross-reactions, with bidirectional cross-reactivity occurring between Bw41, Bw50, Bw60 and Bw61. Antisera were studied that showed; (1) cross-reactivity between Bw44, Bw45 and Bw60 stimulated antisera and both subdivisions of the B12 and B40 antigens; (2) cross-reactivity between B13, Bw44, Bw49, Bw60 and Bw61 stimulated antisera and Bw47; and (3) cross-reactivity between Bw44, Bw49, Bw60 and Bw61 stimulated antisera and B13, with bidirectional cross-reactivity occurring between B13, Bw60 and Bw61 and between B13 and Bw44. Bidirectional cross-reactivity was also observed between B37 and Bw44 and between B7 and Bw60. HLA-Bw48 was shown to be included within the reaction range of both B7 and Bw60 stimulated antisera. Preferential cross-reactivity with one of two antigen subdivisions was extensively observed and occurred exclusively between antigens of the same Bw4/Bw6 association as the antiserum stimulating specificity. The results are discussed within the framework of the existence of multiple shared antigenic determinants.

Antibody Specificity↗