Max R. Mickey

Serotyping for homotransplantation. 18. Refinement of microdroplet lymphocyte cytotoxicity test.

The microdroplet lymphocyte cytotoxicity test was examined thoroughly in an effort to increase the reproducibility of the test. The discrepancy rate in a large series of tests was reduced from 5.16% at the start of this study to the present 0.95% by introducing certain modifications in the technique. Variables connected with the isolation of lymphocytes, handling of antisera, quality of antisera, amount of complement, incubation temperature, duration of incubation, fixing of reactions, and reading of reactions were studied. The method which has resulted appears to be reproducible, simple, and readily usable on a large scale.

Serotyping for Homotransplantation

Abstract During the past four years 104 patients who had received kidneys from either living unrelated or cadaver donors were typed and analyzed, to assess the effect of matching on endogenous crea...

Disturbance of HL-A Antigen Frequency in Psoriasis

Abstract One hundred and fifty-six psoriatic patients had three HL-A specificities significantly altered from expected values; W17 and HL-A13 were found to be markedly increased, and HL-A12 decreas...

Serotyping for homotransplantation. X. Survival of 196 grafted kidneys subsequent to typing.

A total of 196 kidney transplant donors and recipients have been tested with a large panel of antisera and classified as to whether they are matched or mismatched for major leukocyte groups. The survival of the matched patients in comparison to the mismatched patients was then analyzed. During the 21/2 year interval of study, 50 patients have died or have had their rejected kidneys removed. Of these rejected grafts 15 occurred in matched patients and 35 in mismatched patients (P < 0.025). The difference was greater when only retrospectively studied patients who had survived more than 3 months at the time of study were considered. Among 97 patients, 11 deaths have occurred; 10 occurred in mismatched patients whereas only 1 occurred in a matched patient (P < 0.025). The rate of survival in matched recipients was higher than in mismatched patients as shown by the plotting of survival curves (by actuarial methods). Survival after the time of testing was plotted and shown to decline continuously in mismatched patients in comparison to matched patients. An improved technique for the performance of the microdroplet lymphocyte cytotoxicity test is also presented. It is concluded that although survival in this series is associated with matching in marginal limits, many hazards which influence survival especially in the early 3 month period may be making it difficult to demonstrate the association. Further experience, however, will be necessary to rule against transplantation on the basis of the test.

Maternal-fetal incompatibility. I. Incidence of HL-A antibodies and possible association with congenital anomalies.

A large proportion of the sera from 574 parous women was shown to contain cytotoxic antibodies against HL-A tissue antigens. After their second pregnancies, one-quarter of the women had cytotoxins, and after the sixth, one-half of the women had these antibodies. Retrospective studies of the outcome of pregnancies showed that women with antibodies had a significantly higher incidence of infants with congenital anomalies than did those without antibodies. It is postulated that antibodies produced by the mother against incompatible HL-A antigens of the fetus may have a deleterious effect upon the fetus in subsequent pregnancies.

Lymphocytotoxic antibody responses to transfusions in potential kidney transplant recipients.

A series of 737 hemodialysis patients were studied for the relationship between lymphocytotoxic antibody formation and blood transfusions; 331 thereof were studied prospectively. With up to 20 transfusions, highly reactive (greater than 90% reactivity against random panel) antibodies were not found in any of the prospectively studied males or females without previous pregnancies. Nearly 90% of the males failed to form antibodies against greater than 10% of the panel donors. Patients with previous pregnancies developed antibodies at a much higher rate. Among 316 patients tested, antibodies against B cells were found more frequently than antibodies against T cells. Both T and B cell antibody levels often decreased in spite of additional transfusions. It is concluded that the risk of rendering a patient untransplantable because of sensitization as a result of transfusions is very small.

IDENTIFICATION OF UNRESPONSIVE KIDNEY-TRANSPLANT RECIPIENTS

Abstract Non-presensitised kidney-transplant recipients, defined by the absence of lymphocytotoxic antibodies in their serum before transplantation, were divided according to the length of time they were free of cytotoxins. Recipients of cadaver kidneys who had not developed cytotoxic antibodies during haemodialysis treatment of more than one year before transplantation subsequently had a high kidney-transplant survival-rate at one year of 85% in contrast to a 50% survival-rate for recipients who did not develop cytotoxins during a haemodialysis period of less than one year. The statistical significance of the difference between these two groups, comprising 48 and 214 patients, respectively, was (P

Survival and disease patterns in C57BL/6J mice subjected to undernutrition

This study reports survival and disease patterns in a long-lived mouse strain subjected to undernutrition. Four cohorts were studied, each composed of two or more groups of mice, each normally-fed or restricted either pre- and/or postweaning. Restriction prior to weaning was effected by limiting access to the mother. animals restricted postweaning received a nutritionally complete diet, including a normal complement of vitamins and salts, but were fed only 4 portions/week vs 7 portions/week for those animals normally fed—hence the term under-nutrition to differentiate between this and malnutrition. Comparisons of disease patterns among groups revealed that the incidence of lymphoma, the most prevalent tumor, was uniformly decreased in the groups restricted postweaning, with or without preweaning restriction. In the last cohort, deaths of animals with lymphoma were shifted to later ages in the restricted groups, compared with the normally-fed controls. Whereas the lymphoma pattern was considerably modified by undernutrition, the effect on overall survival did not seem as dramatic. Gompertzian parameters for survival past 120 weeks were not statistically different, although with one exception, maximum survival and one of the Gompertzian parameters was consistently greater in groups restricted postweaning, compared with those restricted preweaning only, or not at all. Maximum survival is a parameter not unduly influenced by environmental factors such as infectious disease; consequently, this represents a meaningful effect of undernutrition. Statistically, more significant differences in tumor patterns than in survival suggests that the former are more sensitive to undernutrition than is the latter—at least in this strain of mouse. Greater lifespan prolongation in the restricted animals may be possible through better “fine tuning” of the diet, including improved portion control, particularly in the early postweaning period, to prevent rapid weight gain, and possibly through changes in dietary composition. Finally, it is suggested that undernutrition may exert its effects through an alteration in gene expression.

Serotyping for homotransplantation. XII. Occurrence of cytotoxic antibodies following kidney transplantation in man.

A total of 231 serum samples from 41 patients before and after first and second kidney transplants were investigated for the presence of cytotoxic antibodies. After transplantation 11 of 29 patients had cytotoxic antibodies in contrast to 4 of 21 patients before transplantation. In 10 patients who had their renal grafts removed because of rejection, 9 had demonstrable cytotoxic antibodies. Patients with cytotoxins generally tended to have worse kidney function and transplant failure than patients without cytotoxins (P < 0.005). Moreover, 11 of 14 transplants done in patients with preformed cytotoxins resulted in early transplant failure. From these findings, it appears that humoral cytotoxic antibodies are associated with kidney transplant rejections and that they either act directly on the transplant or serve as indicators of a state of presensitization.

Cadaver-Kidney Transplant Failures at One Month

Abstract Three major factors contributing to early one-day and one-month failure rates were determined in a series of 1899 cadaver-kidney transplantations in over 100 transplant centers in the United States and Canada. The first was that one-month failure rates were greater among 1206 kidneys preserved by continuous perfusion (30 per cent) than among 479 kidneys preserved without perfusion (20 per cent) (p < 0.0001). The one-year survival rate for machine-preserved kidneys was 40 ± 2 per cent as compared to 62 ± 4 per cent for cold-stored kidneys (p < 0.0001). Secondly, a significant association of nonfunction with increasing levels of cytotoxins was found at one day and at one month. In the highly presensitized group 49 per cent of 65 grafts failed in one month. Finally, as expected, warm ischemia time was also progressively detrimental to one-month function. (N Engl J Med 291:1099–1102, 1974)