ABSTRACT
An international collaborative study of 45 transplant centers was undertaken at the 14th International HLA (human leukocyte antigen) and Immunogenetics Workshop to see if HLA antibodies detected posttransplant are predictive of chronic graft failure. With the newly developed assay, MICA (major histocompatibility complex class I-related chain A) antibodies were also measured and their effect analyzed. Total of 5219 sera from patients who were more than 6 months posttransplant with functioning graft were tested for HLA antibodies by enzyme-linked immunosorbent assay, flow cytometry, or Luminex. HLA antibodies were found in 27.2% of kidney patients, 23.6% in the liver, 52.7% in the heart, and 21.7% in the lung. The method of antibody testing did not have a marked influence on the frequency of antibodies detected. MICA antibodies were detected in 15% of kidney patients, 30% of heart patients, and 31% of liver patients. Among 948 kidney patients who had HLA antibodies, 7.3% had rejected their graft within 1 year of testing, compared with 1.7% in 2615 patients without HLA antibodies (P= 0.8 x 10(-17)). Death occurred in 1.4% of total kidney patients and did not correlate to the presence of antibodies. We conclude that patients with posttransplant HLA antibodies indeed have a higher rate of chronic graft failure and that posttransplant antibodies are predictive of chronic rejection.
Subject(s)
Graft Rejection/etiology , HLA Antigens/immunology , Heart Transplantation/immunology , Histocompatibility Antigens Class I/immunology , Immunogenetics , Kidney Transplantation/immunology , Transplantation Immunology , Chronic Disease , Graft Survival , Heart Transplantation/adverse effects , Histocompatibility Testing , Humans , Kidney Transplantation/adverse effectsABSTRACT
Total of 356 women with various types of pregnancy disorders as well as their husbands were classified in four groups regarding the type of the disorder as follows: 1. Recurrent spontaneous abortions (RSA) of unknown etiology (N = 105) and RSA - primary aborters only (N = 84); 2. Blighted ovum (N = 80); 3. Rh immunization in pregnancy (N = 90); 4. ABO immunization in pregnancy (N = 47). Two groups of couples were used as controls: 1. Couples randomly taken from forensic medicine cases of paternity evaluation (N = 104); 2. Couples having two or more children with HLA immunization in pregnancy (N = 78). The couples from all groups were typed for red blood group antigens of ABO, Rhesus, MNSs, Kell, Duffy, Lewis, Kidd and P systems and also for HLA antigens. Significantly higher frequency of antigen HLA-A9 was found in women with RSA (corr. p = 0.0003) and in women with pregnancy disorders caused by Rh immunization (corr. p = 0.0136). In couples with RSA the degree of HLA compatibility was significant (p = 0.0048) and the reactivity of spouses in MLR was significantly decreased (p = 0.0001). Significantly, more low responders in MLR were also found among the women with RSA as compared to the controls (p = 0.0217). Two possible pathologic mechanisms may explain the association between HLA antigens and RSA: 1. immunological defects which are linked to HLA-D/DR region causing malfunction of immunosuppressive mechanisms during pregnancy; 2. endocrinological defect which is linked to HLA region as 21-OH hydroxylase deficiency gene.
