Recipient's HLA-DR phenotype and renal graft outcome.
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Biomedical subjects
Publications and source records attributed to H Betuel.
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The subcellular repartition and the distinctive properties of guanylate cyclase (EC 4.6.1.2) vary according to the lymphocyte population studied and according to the presence of detergent. Guanylate cyclase of non-adherent peripheral lymphocytes and of thymus lymphocytes is recovered by more than 90% in the soluble fraction of the homogenate. Kinetics according to the substrate (5'-GTP-Mn2+) is Michaelian, the Ca2+ ion acts as an activator, especially in the case of blood lymphocytes, and the detergent has no effect on the enzyme activity. On the other hand, the guanylate cyclase of tonsil lymphocytes reside in the particulate fraction. It has non-Michaelian kinetics for the substrate, a strong stimulating effect of detergent, and an inhibitory effect of Ca2+. A comparison of the enzymatic activities of unseparated and of non-adherent tonsil lymphocytes obtained from the same donor points to a correlation between their T and B properties: predominant soluble activity in the T population and particulate guanyl cyclase activity in the B subset.
In a retrospective study involving 24 transplantation centres and 858 cadaveric kidney recipients, a number of transfusion factors affecting transplant survival were identified. The best results were observed with the most intensive transfusion schedules including at least one transfusion per month. The optimal number of transfusions varied from 6 to 20. However, it was impossible to determine whether a minimal interval was required between the last perfusion and transplantation, or whether the effect of each transfusion was limited in time. Qualitatively, it appeared that whole blood and packed red cells gave better results than leucocyte-deprived blood. Moreover, fresh blood taken less than 3 days before the transfusion clearly proved more effective than blood stored for more than 5 days. All this suggests that live leucocytes and platelets may be important factors. The mechanism by which blood transfusions improve the outcome of kidney transplants remains unknown.
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From 1955 through 1978, 150 immunohemolytic accidents of variable gravity have been documented, representing an incidence of 7.1 cases out of 100 000 transfused blood units. These accidents can be classified as follows: 83 cases due to ABO incompatibility, 42 cases due to an irregular antibody in the recipient (six times due to anti-D), 20 cases induced by passive maternal antibodies in the newborn and 5 cases which were attributed to injected anti-A or anti-B antibodies. Ten deaths were recorded, all ascribed to ABO (8 cases) and to Rhesus D (2 cases) incompatibilities. In the present study, a major decrease in the incidence of ABO accidents has been observed, especially since 1966 with systematic controls being performed at the patient's bedside. However, irregular antibodies were the cause of the conflicts in only 10% of the cases when the study was started, and is now incriminated in 8 cases out of 10.
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In a study on the frequency of the HLA A, B, C and DR antigens seen in 100 controls and 31 patients with rheumatoid arthritis, the authors found a significant increase in the DR4 antigen in rheumatoid arthritis. (50% as against 25%; X2 = 8,5; 0,04 greater than Pc greater than 0,008; RR = 3,43). The other antigens on loci A, B. C and DR are not altered significantly. However the increase in DR4 which does not seem to be related to the severity of the rheumatoid arthritis, seems to be proportional to the level of rheumatoid factor. The authors review literature on HLA in rheumatoid arthritis and the figures for the antigenic frequency of HLA-DR4 are compared with their own results. The findings are of interest especially from a pathogenic point of view.
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Celiac disease (CD), which occurs in Europe with varying frequency, is known to be associated with HLA-B8 and even more strongly with HLA-Dw3 because of the high linkage disequilibrium between these two antigens. After typing for HLA-A, -B and -DR antigens in adult patients with CD, we can confirm the high prevalence of B8 (72.7%) and of DRw3 (63.7%). However we find that DRw7 is also significantly increased (54.5%); DRw3 and DRw7, taken together, represent 86% of our 22 patients.
The distribution of human leukocyte antigens (HLA) A and B has been evaluated in the circulatory lymphocytes of 68 patients with spinal cord injury and 32 with severe head injury. Paraosteoarthropathy (POA) was present in 43 spinal cord injury and 23 head injury patients. HLA-B 18 was found in 25.7% of the subjects with POA. Among 341 healthy subjects, the frequency of HLA-B 18 was 7.6%. There is a 0% frequency in patients without POA. The frequency of the HLA-B 18 antigen is significantly raised in POA patients, suggesting relationship between the development of POA and the presence of the HLA-B 18 marker. The presence of HLA-B 18 might be associated with an increased risk of POA in patients with lesion of the central nervous system.
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An infant with a family history suggestive of immunodeficiency presented with combined immunodeficiency. No HLA-A and -B antigens were present on lymphocyte and platelet surfaces, but they were found in the serum. HLA-D determinants were present on lymphocytes. In spite of a fetal thymus transplantation, the infant died of infections associated with the immunodeficiency. The thymus and lymphoid organs were present but hypoplastic and contained few lymphocytes at postmortem examination. The finding of an immodeficiency associated with an absence of cell-surface HLA-A and -B antigens may be regarded as the consequence of the lack of cellular histocompatibility antigens on immune development. Alternatively, other membrane components may have also been defective and partly responsible for the observed abnormalities.
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