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H Dunckley

Publications and source records attributed to H Dunckley.

59 records · Page 4Linked to original sources

DNA typing of HLA-DR antigens in systemic lupus erythematosus.

HLA-DR typing is technically difficult in systemic lupus erythematosus (SLE), where patients have low numbers of peripheral B cells, often of poor viability and weak in antigenic expression. In this series, one third of SLE patients could not be HLA-DR typed by serological techniques, highlighting the potential for systematic bias in DR antigen assignment in studies of HLA and SLE. This potential bias was examined by comparing serological DR results with DNA-DR typing, achieved by examining Taq I fragments of DR beta, DQ alpha, and DQ beta which permitted unequivocal DR phenotyping of all patients, including the 35% for whom conventional DR typing was technically impossible. This showed the success of serological DR antigen assignment was indeed nonrandom, with HLA-DR2 and -DR3 significantly more readily identifiable than DR5 and DRw13. Our study suggests that technical problems may well have contributed to conflicting reports regarding the association of DR2 or DR3 with SLE. Here, DNA-DR phenotyping showed HLA-DR3 is significantly (P less than .05) associated with an increased risk for SLE (54% in 46 patients, 36% in 134 controls) and HLA-DR2 is not.

DNA↗

Deficiency of C4A is a genetic determinant of systemic lupus erythematosus in three ethnic groups.

Systemic lupus erythematosus (SLE) has shown associations with the major histocompatibility complex (MHC) class II DR antigens and class III complement components C2 and C4 in previous studies. The primary susceptibility locus has been difficult to identify, however, on account of linkage disequilibrium within the MHC. We have studied C4A and C4B distributions in 63 Caucasoid, 75 Chinese and 51 Japanese SLE patients. All three populations showed a statistically significant increase in C4A*Q0 (null) alleles when compared with 323 ethnically matched controls. We conclude that complete or partial deficiency of C4A is a genetic determinant of SLE common to these three ethnically distinct populations.

Alleles↗

HLA-DR and -DQ genotyping in anti-GBM disease.

Anti-GBM disease has been associated with the HLA genes of the major histocompatibility complex (MHC) in previous serological studies, with an increased incidence of HLA-DR2 in patients. In this study, 36 patients with anti-GBM disease were genotyped by restriction fragment length polymorphism (RFLP) analysis using cDNA probes for DRB, DQA, and DQB. The frequency of HLA-DRw15(Dw2), a split of DR2, was significantly increased in the patients compared with the controls (63.9 per cent versus 23.3 per cent, chi 2 = 22.4, p(corr) less than 0.0001), and all but one of the patients were positive for either DRw15(Dw2) or DR4 (p less than 0.0001). The frequencies of the remaining DR antigens were not decreased randomly, with a significant decrease in DR7 in the patient group (chi 2 = 8.6, p(corr) less than 0.05). The closely linked gene HLA-DQw6 was found to be significantly increased in frequency in the patients compared with the controls (p(corr) less than 0.0001). No correlations could be made between the genetic data and clinical features of the disease.

Adolescent↗

HLA-DRw15 is increased in frequency in Japanese scleroderma patients.

HLA-DRB allogenotypes were compared in 18 Japanese scleroderma patients and healthy Japanese controls. HLA-DRw15 was found to be significantly increased in frequency in the patient series compared to controls (chi 2 = 4.25, p less than 0.05, Yates' corrected); in DRw15 positive individuals the relative risk of developing scleroderma was 4.0. In Caucasoids DRw11 is significantly associated with scleroderma (Dunckley et al., 1989) and sequence data shows that DRw11 and DRw15 DRB molecules (together with DRw8 where the relative risk of developing scleroderma in Caucasoids is 2.1) share the same amino acid sequence at position 67-70 in the first domain. This would suggest that the DRB1 locus may well be the primary disease promoting locus in scleroderma.

Amino Acid Sequence↗