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Biomedical subjects

C Darke

Publications and source records attributed to C Darke.

At least 19 recordsLinked to original sources
PubMed1992

Frequency of HLA-DPB1 alleles, including a novel DPB1 sequence, in the Northern Ireland population.

HLA-DPB1 allele frequencies in 150 unrelated normal individuals from Northern Ireland were determined using oligonucleotide typing methods. HLA-DPB1*0401 was the most common allele in the population possessed by 75.3% of subjects, followed by DPB1*0201 (20.7%). In addition to these alleles, only HLA-DPB1*0402, -DPB1*0301, and -DPB1*0501 were present in subjects at frequencies greater than 10%. The results in this study are in broad agreement with other Caucasoid studies, but there is regional and ethnic variation in HLA-DP allele frequencies. Three DPB1 alleles were found to be in linkage disequilibrium with HLA-DR antigens determined by RFLP, namely, DPB1*0101 with DRw17 (Dw24 associated) RFLP, DPB1*0501 with DRw13-Dw19 RFLP, and DPB1*1901 with DRw13-Dw18 (Dw25 associated) RFLP. One individual revealed a novel DPB1 pattern of probe reactivity, which following DNA sequencing was found to be HLA-DPB1*2001. To assess the system used and to compare consistency of results between laboratories, 62 cell lines were oligotyped for HLA-DP. The results revealed the system described here to be extremely accurate and showed excellent agreement of HLA-DP typing results for cell lines between laboratories.

Alleles↗
PubMed1990

DQA2 U allele: a genetic marker for relapse of Graves' disease.

The association of HLA-DR3 with Graves' disease in Caucasoids is well established but its significance is unclear and its clinical value as a predictive parameter for relapse after a course of antithyroid drug therapy is controversial. We have further investigated the predictive value at the genomic level in 51 patients with Graves' disease who were treated with a 6-month course of carbimazole and followed up for 2 years. Using DNA-restriction fragment length polymorphism (DNA-RFLP) allogenotyping, (i) complete concordance of HLA-DR assignment was observed between serological and DNA-RFLP analysis of all but one of 51 patients with Graves' disease; (ii) the DR beta 17(1)-DQ alpha 2-DQ beta 2a (a DNA-RFLP allogenotype of the classical Northern European haplotype of HLA-B8 DR3) was significantly (corrected P = Pcorr less than 0.02) associated with Graves' disease particularly in patients who relapsed (Pcorr less than 0.005); (iii) HLA-DR3 was highly associated with DQA2 U allele (chi 2 = 18.53, d.f.2, P less than 0.0005); (iv) a strong correlation between the DQA2 U allele and the outcome of the disease was observed. Relapse occurred in 91% (10/11) of the patients who were homozygous for the DQA2 U allele whilst only 65% (15/23) and 41% (7/17) of patients who were hetero or homo-zygous for the DQA2 L allele (DQA2 U/L and DQA2 L/L) relapsed within the same period of follow-up (chi 2 = 7.18, d.f.2, P less than 0.05). Though the relapse rate in patients with the DQA2 U/U genotype was not significantly higher than the relapse rate in patients with the DQA2 U/L genotype, it was significantly higher than the relapse rate in patients with DQA2 L/L genotype (P less than 0.0001) with a relative risk of 14.3.

Alleles↗
PubMed1990

A long-term follow-up of postpartum thyroiditis.

To investigate the long-term outcome of postpartum thyroiditis (PPT), 43 patients with PPT and 171 control women were evaluated 3.5 (range 2-4) years postpartum. Ten (23%) PPT patients were hypothyroid compared to none of the controls (P less than 0.001). Factors associated with the development of hypothyroidism were high antimicrosomal antibody titre measured at 16 weeks gestation (P less than 0.01), severity of hypothyroid phase of PPT, multiparity, and a previous history of spontaneous abortion. The presence of microsomal antibody but no PPT in one pregnancy did not prevent the occurrence of PPT in the next pregnancy in two patients and a further five patients had PPT in two successive pregnancies. There was no association between HLA haplotype, family history of thyroid disease, smoking or frequency of oral contraception, and the development of long-term hypothyroidism after PPT. It is concluded that permanent hypothyroidism is an important sequel to PPT and patients with PPT should be followed up appropriately.

Adult↗
PubMed1990

Postpartum thyroid dysfunction and HLA status.

Nine-hundred-and-one women presenting in an antenatal clinic at the 60th week of pregnancy were tested for antithyroid antibodies. A group of 113 antibody-positive women and 108 antibody-negative age-matched controls were HLA typed and followed prospectively at 6-weekly intervals through pregnancy and for 12 months postpartum. Forty-five of the women developed biochemical evidence of postpartum thyroid dysfunction (PPTD) of whom 36 were antibody positive. Compared with a local control population (n = 600), and using multiplex analysis, there was a significant increase in the combinations HLA B8, DR3 and HLA A1, B8, DR3 from 22.5% to 40.0% (P less than 0.02) and from 18.6% to 35.6% (P less than 0.01) respectively in the women who developed PPTD. The well-recognized association of these haplotypes with other organ-specific autoimmune diseases provides further support for autoimmune events being implicated in the development of PPTD.

Autoantibodies↗
PubMed1990

Severe intravascular haemolysis in a renal transplant recipient due to anti-B of donor origin.

A group B recipient of a group 0 kidney developed severe intravascular haemolysis due to the formation of anti-B. Immunoglobulin allotyping of donor serum, recipient serum and 'unexpected' anti-B antibody showed the antibody to be of donor origin. The patient and donor genotypes were Gm 3;5/3;5 and Gm 1,2;21/1;21, respectively, and the anti-B antibody allotype was Gm 1;21. The group B recipient of the other donor kidney showed no evidence of haemolysis. Possible factors influencing the occurrence and severity of post-transplantation haemolysis are discussed. The production of anti-A or anti-B antibodies in non-group 0 patients who receive group 0 organ transplants is well described [1-8]. We report a case of severe intravascular haemolysis in a group B patient who received a group 0 kidney, together with immunoglobulin allotyping studies which show conclusively that the antibody responsible for the haemolysis was of donor origin.

ABO Blood-Group System↗
PubMed1990

Spontaneous lymphocyte proliferation in severe periodontal disease: role of T and B cells.

Spontaneous proliferation of T cells, B cells and unseparated lymphocytes was studied in patients with severe periodontal disease and control subjects. In the patient group only, spontaneous lymphocyte proliferation was reduced, whereas B cell proliferation was enhanced. The findings offer further support for the existence of a disturbance in immune regulation in patients with severe periodontal disease.

Adult↗
PubMed1990

Primary standardization for the ELISA of serum thyroperoxidase and thyroglobulin antibodies and their prevalence in a normal Welsh population.

This paper describes the use of ELISA techniques, together with university available primary standards, for the assay of the thyroid autoantibodies anti-thyroperoxidase (TPOAb) and anti-thyroglobulin (TgAb). The data obtained using ELISA compared well with that obtained by passive haemagglutination giving correlation coefficients of 0.79 and 0.83 respectively. TPOAb and TgAb concentrations were assayed in serum samples from 832 healthy individuals aged between 18 and 45 years and cut-off values for both antibodies have been defined (TPOAb less than 19.6kIU/l; TgAb less than 98kIU/l). Applying these cut-off values, some 10% of the population showed elevated anti-thyroid antibody activity and, when divided by sex, a majority of this group belonged to the female population.

Adolescent↗
PubMed1989

A miniaturised method for immunoglobulin allotype serology.

A modification of the classic haemagglutination inhibition method for immunoglobulin allotyping is described which employs reagent volumes of 2 microliters compared with the 25 microliter volumes commonly used in other serological allotyping methods. No loss of sensitivity or specificity was associated with the miniaturised method when compared to the standard tile technique. This method simplifies the large scale phenotyping and screening of sera and permits considerable savings of valuable reagents to be made.

Gene Frequency↗
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↗