Biomedical subjects
Publications and source records attributed to C Darke.
HLA-DRw6 incidence was high in male responders to the Rhesus-D antigen (50%) compared to male non-responders (15.4%), P less than 0.02, P corrected N/S, pregnancy immunized females (23.1%) and a random population (26%). No Bf allotype frequency differences were found among these four groups.
A study of the HLA-A, B and DR antigens and properdin factor B allotypes of 26 patients with lichen sclerosus et atrophicus and a normal control population showed an increase in the HLA-Aw31 antigen only. However, when the HLA-A and B frequencies were combined with the results of a previous independent study a significant increase in both HLA-Aw31 and HLA-B40 was noted. These findings suggest an association between lichen sclerosus et atrophicus and the HLA system.
Cross-reactivity between antigens of the HLA-B7 cross-reactive group (B7 CREG) was investigated by the serological analysis of 60 "broad" cytotoxic HLA antisera produces by pregnancy alone, the HLA typing of the antiserum donors and the identification of their immunizing antigens. Thirty-five sera, made in response to B7, covered (as a group) HLA-B7, B27, Bw42, Bw48, Bw54, Bw55, Bw56, Bw60 and Bw61--the B7 CREG antigens. Bidirectional cross-reactivity occurred between the B7 antigen and B27, Bw55, Bw56 and Bw60 antigens but not between the major B7 CREG antigens B27, Bw22 and B40. HLA-B27 stimulated antisera included B7, B13 and Bw47 within their reaction range and Bw55/Bw56 cross-reacted with Bw42, Bw54, Bw57, Bw58, Bw62 and Bw63. Bidirectional cross-reactivity was observed between Bw55 and Bw57. Fourteen responders possessed an antigen cross-reactive with their immunizing antigen. These findings are discussed in relation to the sharing of determinants by pairs and "families" of HLA antigens.
Seventy-nine cases of Caplan's lung were typed for HLA-A and B antigens. The antigen Bw45 was present only in those patients with rheumatoid factor and was of significantly higher frequency (13.6%) when compared to a non-coal dust exposed population of 316 (1.0%). Those patients without rheumatoid factor showed an increase in HLA-A1 and B8 (58.6% and 51.7% respectively) when compared to the rheumatoid factor positive group (29.6% and 25.0% respectively). Clinical and radiological reassessment were performed on 49 of these patients who were also typed for HLA-DR antigens and properdin factor B allotypes. HLA-DR4 was raised in the rheumatoid factor positive group with rheumatoid arthritis (55.2% compared to 25.8% in the non-coal dust exposed group and 37.3% in coalworkers with normal radiographs). The HLA-DR results are comparable to those found in other studies of rheumatoid arthritis not associated with pneumoconiosis. The findings for HLA-A1, B8 and DR4, however, were not significant after correction was made for the number of antigens tested for. No particular Bf allotype was found to be associated with either the lung change or the arthritis. The induction of the pulmonary lesion in Caplan's syndrome is discussed in relation to the HLA findings.
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The serological analysis of 24 HLA antisera, produced by pregnancy alone, containing B14 and up to six additional specificities was carried out on a selected lymphocyte panel of 316 cells. HLA typing was performed on the antiserum donors and 21 of their husbands. The results show (i) bidirectional cross-reactivity between B8, B14.1, B14.2, B18 and Bw39: (ii) cross-reactivity between antibodies to these specificities and Bw22 (probably Bw22.1 (Cw3 associated) only): (iii) confirmation, with five antisera, of the cross-reactivity between anti-B14 and B5 (with evidence for the cross-reaction being with Bw51 and not Bw52): (iv) cross-reactivity between anti-Bw39 and B37: (v) evidence for unidirectional cross-reactivity between anti-Bw38 and B8, B14.1 and B14.2: (vi) preferential cross-reaction with the subdivisions of B14 (anti-B8 with B14.2 and anti-Bw39 with B14.1). The concept of "shared antigenic determinants" is briefly discussed in relation to these findings.
The minimal sequential absorption of 12 HLA-B14 antisera with B14 positive cells provided 10 antisera that showed a high correlation (r values > 0.8) with the original B14.1 and B14.2 sera of Dewar et al. (1977). The subdivisions defined by the absorbed sera corresponded to the B14 subtype of their immunizing cell. The subtyping of 112 B14 positive individuals showed the frequency of B14.1 to be 33.04%. B14 heterozygous individuals always typed for one but never for both subdivisions. Analysis of a population of 2,044 showed B14.1 to be in linkage disequilibrium with Aw32 and B14.2 with Aw33, Aw30 and A3. It is concluded that B14.1 and B14.2 are distinct antigens which, in the population tested, comprise the entire specificity of HLA-B14.
An HLA-Bw45 serum (Mu46), which was produced by pregnancy in a Bw44 positive woman, is described. The serum was unable to be absorbed by Bw44 positive cells. Blocking tests employing broad B12 (Bw44 + Bw45) antisera, stimulated by either Bw44 or Bw45, showed that only F(ab)'2 from Bw45-stimulated B12 sera would completely block the cytotoxicity of this serum. It was concluded that Bw44 and Bw45 are distinct specificities which share common determinants. These findings are briefly discussed in relation to a recent report on the HLA-B antigen and supertypic Bw4, Bw6 antigen relationship.
Previous studies of HLA antigen frequencies in asbestos related pulmonary fibrosis have suggested some weak associations both with susceptibility to the disease (B12 and B27) and protection from the disease (B18 and Bw35). HLA typing was performed on a further series of 64 asbestos workers with no chest abnormality and 166 workers with various radiographic changes, 78 having pulmonary fibrosis. The results fail to give statistical confirmation of these associations although B27 was twice as frequently associated with pulmonary fibrosis and diffuse pleural thickening. Analysis of the combined data from this and four other studies failed to show any consistent associations.
HLA typing was performed on 267 Welsh coalworkers with pneumoconiosis (96 cases of simple pneumoconiosis, 115 cases of progressive massive fibrosis and 56 cases of Caplan's Syndrome) and 134 coalworkers with no abnormality. The presence or absence of rheumatoid factor was also determined. The results fail to confirm a previously reported increase in HLA-A1 and B18 in coalworkers with no pneumoconiosis. When correction was made for the number of antigens typed (i) HLA-Bw21 was significantly increased from 1.1% in the total group with pneumoconiosis to 8.2% in coalworkers with no abnormality (P corrected less than 0.032); (ii) HLA-Bw45 was increased in Caplan's Syndrome (10.7%) and Caplan's Syndrome patients with rheumatoid factor (16.1%) when compared to a non-occupationally exposed control group (0.8%) (P corrected = 0.019 and 0.0064 respectively). These results were not significant when comparisons were made with the coalworker group with no abnormality. The apparent higher frequency of Bw45 in Welsh coalworkers is discussed.
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The application of a simple batch method for the isolation of IgG from weakly lymphocytotoxic sera is described. The use of purified IgG as an antibody source at the serum concentration or up to tentimes that level resulted in the conversion of 25 out of 28 previously weak or non-reactive cytotoxic sera into potentially useful tissue typing reagents. The sensitivity of this technique was assessed by comparison with five cytotoxic test systems.
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Serum thyroid autoantibodies to thyroglobulin (TG) and thyroid microsomes (M) were measured by ELISA prospectively in 37 manic depressive patients prior to receiving lithium carbonate and during therapy with this drug for a mean of 16.2 months. They were also measured once in 27 normal subjects and several times in five psychiatric patients not receiving lithium. Sixteen patients (43%) had either thyroglobulin, microsomal antibodies or both before receiving lithium therapy. During therapy significant fluctuations in antibody titre, both upwards and downwards were observed in ten out of 12 patients with M antibodies and in nine out of 11 with TG antibodies. The fluctuations in antibody titre are consistent with an immunomodulatory effect of lithium as has been shown in animal studies. It is suggested that psychiatric patients should have thyroid antibodies measured routinely before and during lithium therapy.