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Biomedical subjects

J R Batchelor

Publications and source records attributed to J R Batchelor.

At least 127 records · Page 7Linked to original sources
PubMed1980

HLA-DR antigens and toxic reaction to sodium aurothiomalate and D-penicillamine in patients with rheumatoid arthritis.

To investigate the possible relation between certain HLA antigens and toxicity during treatment with sodium aurothiomalate of D-penicillamine, we studied 91 patients with rheumatoid arthritis. Seventy-one had toxic reactions to either drug or both drugs; the remaining 20 took one of the drugs for at least six months, without toxicity. Nineteen of 24 patients in whom proteinuria developed were positive for HLA-B8 and HLA-DRW3 antigens; 14 of 15 episodes of aurothiomalate-induced proteinura and nine of 13 episodes of penicillamine-induced proteinura occurred in patients with these antigens. All 13 episodes of proteinuria in which urinary protein exceeded 2 g in 24 hours occurred in patients with DRw3. The relative risk of proteinuria during treatment with aurothiomalate is increased 32 times in patients who are HLA-DRw3 positive. No significant associations were found between any HLA antigen and development of skin rashes or hematologic complications. Toxicity during aurothiomalate or penicillamine treatment for rheumatoid arthritis may be under genetic control.

Adult↗
PubMed1980

Hydralazine-induced systemic lupus erythematosus: influence of HLA-DR and sex on susceptibility.

26 patients with systemic lupus erythematosus (SLE) induced by treatment with the antihypertensive drug hydralazine were investigated to determine if predisposition to the toxic effect was associated with an HLA-DR antigen. 25 of the 26 patients were slow acetylators. The group was compared with three others (1) 113 healthy subjects, untested for acetylator phenotype, (2) 16 slow-acetylator hypertensive patients treated with hydralazine for more than a year without developing SLE, and (3) 20 patients with idiopathic SLE. The frequency of HLA-DR4 (73%) was significantly higher in the group with hydralazine-induced SLE than in the other groups (respectively 33%, 25%, and 25%). The ratio of women to men affected was 4:1. If the slow acetylators treated with hydralazine were analysed as one group, it was observed that all women with DR4 developed hydralazine-induced SLE; the only men to do so were those with DR2 who were receiving 200 mg hydralazine per day. These observations have led us to suggest guide lines for hydralazine therapy and point to a striking association between an HLA-DR antigen and an adverse reaction to a therapeutic agent. It was also noted that the distribution of DR antigens in the hydralazine-SLE patients was significantly different from that in the group with idiopathic SLE. This supports the view that the syndromes are separate entities.

Acetylation↗
PubMed1979

Failure of long surviving, passively enhanced kidney allografts to provoke T-dependent alloimmunity. I. Retransplantation of (AS X AUG)F1 kidneys into secondary AS recipients.

Long survival of (AS X AUG)F1 rat kidney allografts in AS recipients was induced by passive enhancement with AS anti-AUG antiserum at the time of grafting. After 1-3 mo, the kidney allografts were transferred to second AS recipients, either naive or sensitized against AUG tissue. Naive second recipients did not reject the grafts acutely and failed to mount T-dependent immunity against AUG targets. When later challenged with spleen cells carrying the AUG haplotype, the naive second AS recipients showed strong IgM, IgG, and cytotoxic T-cell responses after grafting, and the kidneys were rapidly destroyed by immune rejection in all but one rat. It is concluded that long-surviving kidney allografts fail to activate helper T cells and induce in naive second recipients the same state of unresponsiveness observed in the first recipient.

Animals↗
PubMed1979

Failure of long surviving, passively enhanced kidney allografts to provoke T-dependent alloimmunity. II. Retransplantation of (AS X AUG)F1 kidneys from AS primary recipients into (AS X WF)F1 secondary hosts.

Long surviving, passively enhanced (AS X AUG)F1 kidneys carried by AS recipients were retransplanted into (AS X WF)F1 second hosts. Acute graft rejection did not occur. Only one of six secondary recipients mounted a significant T-dependent IgG lymphocytotoxic antibody response. In all six, generation of cytotoxic T cells was markedly slower and depressed. These results are compatible with the hypothesis that kidney parenchyma, although carrying major histocompatibility complex specificity is able to induce T-independent but not T-dependent alloimmunity. A corollary is that passenger cells are responsible for exciting the T-dependent allimmune response normally observed after grafing. The practical difficulty of eliminating all T-dependent immunogenicity from (AS X AUG)F1 kidneys was emphasized by the observation that a 3-d residence in an intermediate AS recipient was insufficient time to prevent acute graft rejection after retransplantation.

Animals↗
PubMed1979

An immunogenetic basis for the tissue involvement in Behçet's syndrome.

The multifocal involvement in Behçet's syndrome was grouped into a spectrum of four types, three of which appeared to have an immunogenetic basis. HLA-B5 was related to the ocular type of Behçet's syndrome (relative risk 7.3), HLA-B27 to the arthritic type (relative risk 12.1) and HLA-B12 to the muco-cutaneous type (relative risk 3.9). The concept that recurrent oral ulceration and Behçet's syndrome may belong to a disease spectrum is substantiated by the natural course of the disease. Furthermore, patients with recurrent oral ulcers share with the muco-cutaneous type of Behçet's syndrome a significantly increased frequency of HLA-B12 (relative risk 2.6). The HLA markers may also prove to be significant in the differential diagnosis and prognosis of a disease which may present under a confusing variety of clinical manifestations.

Adolescent↗
PubMed1978

Genetic basis of rheumatoid disease: HLA antigens, disease manifestations, and toxic reactions to drugs.

Ninety-five patients with rheumatoid arthritis and 200 healthy controls were examined for HLA-D-related (HLA-DR) alloantigens. HLA-DRW4 was significantly more prevalent among the patients and was particularly common in those with a family history of the disease (77% of such patients had DRW4 compared with 34% of controls). Significantly fewer patients than controls had DRW2: patients with this antigen had rheumatoid nodules less frequently and significantly lower titres of rheumatoid factor than patients without DRW2. In contrast DRW3 was significantly more prevalent among severely affected patients with rheumatoid factor titres exceeding 1/1280 and in patients with nodules. There was a significant association between DRW2 and DRW3 and toxic reactions to sodium aurothiomalate and penicillamine. The results suggest that the HLA-DR phenotype is associated not only with susceptibility to rheumatoid arthritis but also with severity of the disease and whether certain toxic reactions to drugs occur.

Adult↗
PubMed1978

Strong association between HLA-DRW2 and antibody-mediated Goodpasture's syndrome.

In a study of HLA types in Caucasian patients with nephritis due to antibodies to glomerular basement membrane, antigen frequencies at A, B, or CW loci were normal. However, 15 out of 17 (88%) patients to whom DRW types were definitely assigned had HLA-DRW2 compared with 32 out of 100 Caucasian blood-donors. This difference is highly significant.

Anti-Glomerular Basement Membrane Disease↗
PubMed1978

Factors influencing the risk of multiple sclerosis developing in patients with optic neuritis.

One-hundred and forty-six patients who had presented with optic neuritis but without evidence of demyelination elsewhere in the nervous system, and in whom no specific cause could be identified, were reassessed clinically between one month and twenty-three years after the onset. Fifty-eight patients (40 per cent) had developed MS. All 146 patients were HLA-typed. Three factors were identified which were significantly associated with the development of MS: positive typing for the HLA antigen BT 101, winter onset of the initial attack of optic neuritis in BT 101-positive patients only, and recurrent attacks of optic neuritis. The application of these results to the individual patient is of limited use. However, recurrent attacks of optic neuritis should be given the same significance in the clinical classification of MS as episodes of demyelination occurring elsewhere in the central nervous system in a patient with a previous attack of optic neuritis. The results suggest that optic neuritis is caused by two different environmental agents or groups of agents and that the agent which is most common in the winter leads to the development of MS in the genetically susceptible individual. The agent more common in the summer is much less likely to cause MS in either suscetible or non-susceptible individuals. The biological role of the HLA system in the handling of foreign antigens is discussed and it is suggested that the presence of the HLA antigens associated with MS confers a specific disadvantage on individuals in the ability to handle infection by the MS causative agent and that this allows damaging immunological processes to develop.

Diagnosis, Differential↗