Gene frequencies and genetic linkage disequilibrium for the HLA-linked genes Bf, C2, C4S, C4F, 21-hydroxylase deficiency, and glyoxalase I.
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Biomedical subjects
Publications and source records attributed to M S Pollack.
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To document further the proposed genetic linkage between congenital adrenal hyperplasia due to 21-hydroxylase deficiency and HLA, 34 unrelated families from New York and Zurich, with a total of 48 patients, 48 siblings and their parents, were studied. All patients were HLA genotypically different from the healthy sibs; when two or more children were affected in the same sibship they were always HLA-B identical. The gene for 21-hydroxylase deficiency was separated by genetic recombination from the HLA-A locus and from the locus for glyoxalase I-polymorphism. No HLA-A, HLA-B or HLA-C antigen was selectively increased among the 34 unrelated patients. Lod-score analysis for HLA-B:21-hydroxylase deficiency gave a peak for theta approximately 0.00 at 5.20 for females and 4.30 for males, giving a total peak lod score of 9.5 at theta approximately 0.00 when male and female lod scores were combined. Close genetic linkage between HLA-B and 21-hydroxylase deficiency was thus established.
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Selective adsorption of several common "monospecific" HLA typing sera with HLA typed platelets, purified B lymphocytes, cultured lymphoid cells, or lymphocytes from patients with active chronic lymphocytic leukemia demonstrated that many of these sera contain antibodies to non-HLA antigens. Antibodies were detected to antigens present on peripheral blood B-lymphocytes, cultured lymphoid cells and leukemic cells from patients with both myelocytic and lymphocytic forms of leukemia but absent from T-lymphocytes and platelets. Since these kinds of antibodies appear to be present in a large proportion of common HLA typing sera, caution should be used in interpreting all data related to HLA antigen expression in leukemia.
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Several laboratories have recently observed that common HLA typing sera contain antibodies to various nonHLA antigens, including leukemia-associated antigens and normal platelet, granulocyte, or B-lymphocyte-specific alloantigens. In order to study the possible effects of these antibodies on HLA typing data in leukemia, several of these sera were adsorbed with HLA typed platelets, purified B-lymphocytes, cultured lymphoblasts, or mononuclear cells from patients with active leukemia of various types, and retested for residual activity against previously reacting cells. The results indicate that many of the reactions of leukemia cells to HLA typing sera represent reactions to nonHLA antibodies, many of which are directed against antigens common to cultured lymphoblasts, leukemia cells of several types, and normal B-cells. In the absence of family studies or prior serum adsorption, caution should be used in interpretation of all data related to HLA antigens in leukemia.
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Antiglobulin reagents have been reported to increase the sensitivity of lymphocytotoxicity procedures for the detection of HLA antibodies that may affect the survival of transplanted kidneys or cause nonhemolytic transfusion reactions. This paper describes how such a procedure may also be used to demonstrate the presence of specific HLA antibodies in sera containing anti-Bg antibodies but lacking HLA antibodies that can be detected by conventional procedures. With the use of more sensitive procedures for the detection of both anti-Bg and HLA antibodies, studies of the relationship between specific HLA and Bg antigens can be extended, and the genetics of the expression of the Bg antigens can more easily be studied.
Recent technical achievements allow satisfactory cryopreservation of human platelets that, after thawing and washing, maintain functional viability for therapeutic use. We have now demonstrated that such previously frozen platelets retain full HLA antigenic activity in spite of the combination of freezing, thawing, and washing procedures and the presence of the surface-active cryopreservative DMSO. Platelets stored at 4 C without DMSO and previously frozen platelets from the same donors were tested in parallel for quantitative expression of HLA antigens. In all cases, the previously frozen platelets were quantitatively equal or superior to the platelets stored at 4 C with regard to their capacity to specifically reduce the HLA antibody activities of selected typing sera against a panel of antigen-positive lymphocytes.
Eighty-five patients with thalassemia and all available immediate family members were typed for HLA-A,B, C, and DR antigens, and the patients were tested for clinical diabetes and white cell antibodies in response to multiple blood transfusions. The antigen Bw35 was increased among both patients and their parents. This finding is consistent with previous data suggesting that this antigen may offer an independent selective advantage in populations at risk for both thalassemia and malaria. No association of the HLA system to the development of diabetes was noted. A wide variation was observed in the degree of white cell antibody response to transfusions: 25 of the 84 patients tested had significant levels of white cell antibodies while the majority (49) of the patients had essentially no antibodies. The frequency of the antigen DR2 was significantly increased in the high-response group, while the antigens Bw35 and DR7 were significantly increased in the low-response group. This finding suggests that an HLA-linked immune response or immune suppression factor or an HLA-linked susceptibility to iron toxicity may play a role in the development of these antibody responses.
Three cases of acute mediastinitis secondary to staphylococcal sternoclavicular pyarthrosis are reported. In each case, the patient presented with minimal signs and symptoms and mediastinitis was not suspected until demonstrated by preoperative CT. Since septic arthritis of the sternoclavicular joint may be insidious in onset and is associated with a high incidence of life-threatening secondary mediastinitis, CT is recommended as the initial imaging study in the evaluation of unexplained sternoclavicular joint pain and swelling.
Serologic HLA typing was performed on 29 patients with infantile spasms and hypsarrhythmic patterns in their electroencephalograms (EEGs). There were no significant increases in the frequencies of HLA-A, B, and C antigens in the infantile spasm group as compared with controls. However, there was a significant increase in the frequency of DRw52 in the infantile spasm patients (90%) as compared with controls (72%) (p less than 0.05). In addition, 3 of 12 white infantile spasm patients demonstrated the complete B18,DR3 (DRw52) haplotype; none of 150 control white subjects showed this haplotype. These findings contribute to evidence that immunological mechanisms may be involved in the pathophysiology of infantile spasms.
The HLA antigens system is extremely polymorphic, and HLA typing is now widely used for both the exclusion and the positive assignment of paternity. We have also used HLA typing for identification of paternity of fetal cells in a pregnancy detected a few weeks after the rape of a woman. The HLA typing indicated that the father of the fetus was the woman's husband, with a probability of 25:1 (96%), before the time the rapist could also be tested. Subsequently, the accused rapist was excluded as a potential father because he lacked all of the paternal antigens detected in the fetus. This prediction was confirmed after delivery.