Panic disorder in genotypic HLA identical sibling pairs.
The authors describe two HLA identical sibling pairs with panic disorder. To their knowledge, this is the first report of histocompatibility testing in patients with anxiety disorders.
Biomedical subjects
Publications and source records attributed to T C Fuller.
The authors describe two HLA identical sibling pairs with panic disorder. To their knowledge, this is the first report of histocompatibility testing in patients with anxiety disorders.
Previous studies have indicated that HLA-DR homozygous cell lines express two Ia alpha and Ia beta chains that combine to form at least two Ia molecules. This report demonstrates by two-dimensional gel electrophoresis the existence of a third structurally distinct human Ia beta chain on DR2 and DR5 cell lines. This suggests that at least five separate genes control the expression of Ia molecules on HLA-DR homozygous cell lines.
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The addition of an antihuman immunoglobulin (AHG) reagent to the basic complement-dependent cytotoxicity (CDC) test markedly increases the frequency of lymphocyte-reactive antibodies in many alloantisera. The extra reactivity has been previously identified as associated with alloantigens coded by the HLA complex, but definitive evidence establishing the antigenic specificity of the antibodies reactive by AHG-CDC has been lacking. We determined the nature and specificity of AHG-reactive alloantibodies through parallel testing (CDC +/- AHG) of a large battery of HLA alloantisera against panel cells composed of unrelated individuals and genotypic HLA-identical sibling pairs, and by means of differential platelet absorption and elution of alloantibody. We conclude that the AHG-CDC procedure, relative to "standard" CDC, detects subthreshold levels of alloantibody with specificity for the HLA-A, B, and C locus alloantigens. Most importantly, the AHGG-CDC technique consistently converts cytotoxicity-negative absorption-positive (CYNAP) HLA alloantibody to direct cytotoxic antibody, thus providing a more accurate assessment of the complete specificity of antibodies in complex alloantisera and patients' sera without having to resort to more cumbersome binding assays. These data should be of assistance in improving the characterization of HLA alloantisera used for serological and biochemical studies of the HLA molecules and in delineating the specificity of AHG-CDC antibody in clinical allotransplantation and single-donor platelet transfusion.
The human class II, HLA-linked, B cell alloantigens include the HLA-DR, MB, MT, and Te determinants. Interest in the molecular relationships of these antigens has recently intensified because of their homology to the murine Ia antigens and their possible importance in disease predisposition and transplantation. We have used alloantisera with carefully defined immunochemical as well as serologic specificity, and two immunochemical techniques, sequential immunoprecipitation with analysis by SDS-PAGE and two-dimensional gel electrophoresis, to explore the molecular relationships of the MT2, MB3, MT4, and HLA-DR5 antigenic determinants. The data presented here indicate that 1) all class II molecules that bear the DR5 antigenic determinant also bear the MT2 antigenic determinant; (2) the homozygous DR5 cell line, Swei, expresses at least two structurally distinct class II molecules, both of which bear MT2: one bears the MT2, MB3, and MT4 antigenic determinants, and the second bears the MT2, but not the MB3 or MT4 antigenic determinant; and (3) the DR5 determinant is located on at least one and possibly both of these distinct class II molecules.
Neuraminidase (Vibrio cholerae) treatment of human metastatic mammary carcinoma MDA-MB-231 cells grown in culture released 0.60-0.63 mg of N-acetylneuraminic acid from 10(9) cells. Incubation of intact cells with a modified trypsin and fractionation by gel filtration gave mainly O-glycopeptides. The presence of O-glycosyl-linked chains having one or two carbohydrate residues was confirmed by treatment of the glycopeptide fractions with galactose oxidase, followed by reduction with alkaline sodium borotritide and fractionation. The major glycopeptide fraction, which consisted of 53% carbohydrate and 47% protein, and a minor glycopeptide fraction each inhibited hemagglutination by peanut lectin. These results suggest the presence of O-beta-D-galactopyranosyl-(1 leads to 3)-O-(2-acetamido-2-deoxy-alpha-D-galactopyranosyl)-(1 leads to 3)-L-serine (threonine) residues. The absorptive capacities for anti-HLA-A2 and anti-HLA-B8 antisera were slightly greater for intact than for lyophilized cells, which suggested that masking of these major histocompatibility antigens did not occur in intact cells.
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Cell-mediated and humoral immune responses against antigens associated with primate C-type oncoviruses were evaluated in humans by microcytotoxicity and radioimmunoprecipitation assays. Five of six women tested sequentially during pregnancy developed selective cell-mediated reactivity against baboon endogenous virus (BEV)--infected human fibroblasts. Responsiveness peaked during the second and third trimesters and corresponded temporally with elevated antibody levels to BEV antigens. Similar cell-mediated reactivity was not observed in nonpregnant individuals. Selective cell-mediated reactivity directed against cells infected with the simian sarcoma virus-simian sarcoma associated virus complex (SSV--SSAV) was observed in four of 20 healthy adults (three of 14 nonpregnant, one of six pregnant). These observations suggest that cell-mediated reactivity against primate C-type oncoviruses is occasionally detected in healthy nonpregnant adults, but that during pregnancy both cell-mediated and humoral reactivity against BEV may become selectively expressed.
The relationship between transfusion of different preparations of blood, sensitization to HLA antigens and survival of subsequent kidney transplants was investigated in 90 consecutive recipients. HLA lymphocytotoxins in transplant candidates precluded or greatly delayed receipt of an allograft (p less than 0.0005). Furthermore, only 17% of such sensitized recipients had functioning grafts one year after transplantation compared to 57% survival for nonsensitized recipients (p less than .02). A small number of nonsensitized patients who were never transfused had surprisingly poor one year graft survival (25%). If frozen blood is used for transfusion rather than whole/packed RBC, the incidence of patient sensitization can be markedly reduced without subsequent compromise in transplant survival (51%). It is concluded that as a consequence of avoiding HLA sensitization by transfusion of frozen blood (processed by agglomeration), the period of hemodialysis required for potential graft recipients will be shortened and an increased proportion of potential recipients will be successfully treated by transplantation.
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Histocompatibility (HL-A) phenotypes of 44 unrelated white patients from the greater Boston area with amyotrophic lateral sclerosis (ALS) and 200 white controls were compared. In the overall ALS group, an increased frequency of HL-A3 was noted (43% vs 25%, P less than .05). Thirty-eight patients had rapidly progressive disease; among this group the HL-A3 incidence was 50% (P less than .005). Six patients had slowly progressive disease, none had HL-A3, and five had HL-A12. The HL-A antigens may link with disease severity in ALS.
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