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Biomedical subjects

G E Rodey

Publications and source records attributed to G E Rodey.

At least 55 records · Page 3Linked to original sources
PubMed1982

Molecular relationships of the human B cell alloantigens, MT2, MB3, MT4, and DR5.

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.

Absorption↗
PubMed1981

Mitral valve prolapse: a consistent manifestation of type IV Ehlers-Danlos syndrome. The pathogenetic role of the abnormal production of type III collagen.

To evaluate whether abnormal production of type III collagen, the characteristic biochemical feature of patients with the type IV Ehlers-Danlos syndrome, consistently predisposes to mitral valve prolapse, we evaluated the family of a proband with classic type IV Ehlers-Danlos syndrome. Production of type III collagen was assessed with the use of cultured skin fibroblasts. Mitral valve prolapse was detected by M-mode and two-dimensional echocardiography. Biochemical abnormalities in the production of type III collagen and echocardiographic findings of mitral valve prolapse were completely concordant. All patients with abnormal production of type III collagen had mitral valve prolapse and all subjects with normal production of type III collagen had entirely normal echocardiograms. Six of the eight patients with abnormal production of type III collagen had subtle cutaneous abnormalities. The consistent association of abnormal production of type III collagen and mitral valve prolapse in this family suggests that this abnormality of collagen may give rise to mitral valve prolapse.

Adolescent↗
PubMed1981

Functional characteristics of TG and TnonG cells in a three party MLR.

Human peripheral blood T lymphocytes were separated into highly purified Fc gamma receptor-positive (TG) and negative (TnonG) populations. These subgroups were compared with unseparated T cells for their ability to proliferate in response to concanavalin A or allogeneic cells, and to suppress a mixed leukocyte culture reaction (MLR). TG cells fail to vigorously proliferate in response to Con A or irradiated allogeneic cells. Moreover, the response of TnonG populations to Con A and allogeneic cells is enhanced compared with unseparated T cells, suggesting active suppression by TG cells. The suppressive effects of TG cells was confirmed in a 3-party MLR. In contrast, TnonG cells failed to suppress the MLR. However, Con A-activated TnonG cells did suppress the MLR and were as effective as TG cells.

Concanavalin A↗
PubMed1981

Current understanding of the complexity of the HLA antigen system.

The beneficial effect of HLA matching in allotransplantation and the associations of HLA antigens with a variety of diseases are probably manifestations of a more basic function of self-discrimination and immune regulation served by the HLA complex. Despite these important conceptual advances, the specific HLA determinants and the exact mechanisms which favor allograft survival are still undetermined, as are the mechanisms of disease susceptibility conferred by the HLA complex. The currently recognized HLA loci may be only the top of a larger iceberg, and it is likely that additional important loci and functions will be defined in time to come.

Absorption↗
PubMed1980

HLA public determinants are target antigens of cell-mediated cytotoxicity.

HLA public antigens X and Y have been shown to be common determinants on the heavy chains of molecules belonging to the HLA-B7 and HLA-B5 cross-reactive groups (CREG), respectively. The ability of these antigens to act as targets for cytotoxic lymphocytes was investigated. After stimulating B7-CREG cells in an in vitro primary and secondary culture with mitomycin-treated B27-positive cells, the effector cells generated lysed cells bearing B7, Bw22, B27, or B40, all of which bear X. No lysis was seen with cells not bearing X. Parallel results were obtained in the B5-CREG, where the effector cells lysed target cells bearing B5, B15, B18, or Bw35, all of which bear Y. No lysis was seen with cells not bearing Y. That these public antigens were the determinants actually recognized by the cytotoxic effector cells was demonstrated by the ability of appropriate antibody to inhibit cytolysis. These results suggest possible immunopathogenic mechanisms that may explain the apparent association of X with spondyloarthropathy and of Y with Behçet's disease.

Cytotoxicity, Immunologic↗
PubMed1980

Association of HLA-DRw4 with rheumatoid arthritis in black and white patients.

The HLA-A, B, C, and DR antigens were typed in 35 black and 35 white Americans with rheumatoid arthritis. The frequency of HLA-DRw4 was increased in both the black and white patient patient groups compared to the race-matched control groups. DRw4 was found in 45.7% of the black patients compared to 14.3% of the black controls (corrected P value < 0.035) and DRw4 was found in 71.4% of the white patients compared to 40.0% of the white controls (corrected P value < 0.035). These data indicate that immunogenetic factors related to DRw4 are important in the development of rheumatoid arthritis in American blacks as well as whites.

Adult↗
PubMed1980

A public antigenic determinant in the HLA-B5 cross-reacting group--a basis for cross-reactivity and a possible link with Behcet's disease.

Serologic cross-reactivity among allelic gene products commonly occurs in the HLA complex, but the molecular basis of these serologic phenomena is incompletely characterized. Because of strong cross-reactivity among antigens comprising the B5 cross-reactive group (i.e., HLA-B5, B15, B18, and Bw35), we initiated a study of the chemical basis of cross-reactivity among this group of antigens. Using classic serologic procedures, an 125I-Protein A binding assay, and chemical immunoprecipitation techniques, we have defined a new antigenic determinant, tentatively designated "Y," which is present on certain HLA-B molecules. By a series of sequential immuno-precipitation experiments, Y was shown to be a "public" antigenic determinant distinct from the "private" determinants B5, B15, B18, and Bw35, but present on the same 44,000 dalton glycoprotein molecules. Although B5 is most highly associated with Behcet's disease, other members of the B5 cross-reactive group have also been associated with Behcet's, albeit to a lesser extent. These associations suggest that determinant Y may play a role in predisposition to Behcet's disease.

Animals↗
PubMed1980

HLA serological cross-reactivity: HLA-B15 has two public antigens.

On the basis of their serologic cross-reactivity, HLA antigens can be organized into cross-reactive groups or CREG's. We have recently defined immunochemically two public alloantigenic determinants X and Y which can account for the serological cross-reactivity of the B7-CREG and B5-CREG, respectively. One of the smaller of these CREG's consists of HLA-B15 and B17. Using microcytotoxicity testing, a fluoresceinated Protein A binding assay, and chemical immunoprecipitation techniques, we have defined a new public alloantigenic determinant, tentatively designated "Z," which is present on the 44,000 dalton glycoprotein chains of HLA-B15 and HLA-B17, but distinct from the B15 and B17 determinants. Since HLA-B15 is also a member of the B5-CREG, and therefore bears allodeterminant Y, this report constitutes the first immunochemical demonstration of two public determinants, Y and Z, on a single HLA-B molecule, HLA-B15.

Absorption↗
PubMed1979

HLA-DR specificities among black Americans with juvenile-onset diabetes.

To study the association of histocompatibility (HLA) genes in black persons with juvenile-onset diabetes, we determined HLA-A, HLA-B, HLA-C and HLA-DR specificities in 40 black Americans with this disease and in 67 unaffected black Americans. Marked increases in the frequencies of HLA-DRw3 and HLA-DRw4 were found in the patients as compared with the unaffected persons: DRw3 was found in 72.5 per cent of patients versus 29.9 per cent of unaffected persons and DRw4 in 72.5 per cent versus 25.4 per cent (corrected P values each less than 0.0007). DRw2 was not found in any of the patients but was present in 26.9 per cent of unaffected persons (P corrected less than 0.035). There is thus a negative correlation between this specificity and juvenile-onset diabetes. By contrast, no meaningful differences were found in the frequencies of A, B, or C locus antigens. Studies in white persons with juvenile-onset diabetes have suggested that the reported HLA-B associations are due to HLA-D region specificities, and our results also support the premise that D region specificities are the primary associations with juvenile-onset diabetes.

Adult↗
PubMed1979

A study of HLA-A, B, C, and DR specificities in pigeon breeder's disease.

The frequencies of HLA-A, -B, and -C antigens were determined among 51 symptomatic pigeon breeders, 102 asymptomatic pigeon breeders, and 100 normal blood donors. The HLA-DR specificities were also studied in 32 symptomatic and 29 asymptomatic pigeon breeders. All subjects were white. Symptomatic subjects were defined by the development of respiratory symptoms or decreased pulmonary function after aerosol challenge with pigeon serum. Asymptomatic subjects were comparably exposed to pigeons but had no pulmonary signs or symptoms after aerosol challenge. No significant association was found between any of the tested HLA specificities and pigeon breeders. This lack of association and the observed paucity of multiplex families indicate that HLA complex genetic factors tested in this study do not favor the development of pigeon breeder's disease in exposed persons.

Alveolitis, Extrinsic Allergic↗
PubMed1979

Public antigenic determinant on a family of HLA-B molecules.

Serologic cross-reactivity among allelic gene products commonly occurs in the HLA complex, but the molecular basis of these serologic phenomena is incompletely characterized. Because of strong cross-reactivity among antigens comprising the B7 cross-reactive group (i.e., HLA-B7, Bw22, B27, B40, and Bw42) and because of the association of several antigens of this group with spondyloarthropathies, we initiated a study of the chemical basis of cross-reactivity among this group of antigens. Using classic serologic procedures, 125I-Protein A binding assay, and chemical immunoprecipitation techniques, we have defined a new antigenic determinant, tentatively designated "X", which is present on certain HLA-B molecules. By a series of sequential immunoprecipitation experiments, X was shown to be a "public" antigenic determinant distinct from the "private" determinants B7, Bw22, B27, and B40, but present on the same 44,000-dalton glycoprotein molecules. The implications of this finding regarding disease predisposition and HLA typing as a diagnostic aid are discussed.

Arthritis, Reactive↗
PubMed1977

Successful transfusion of platelets "mismatched" for HLA antigens to alloimmunized thrombocytopenic patients.

A critical factor limiting the availability of histocompatible platelet transfusions for alloimmunized, thrombocytopenic patients is the large pool of HLA-typed donors needed to procure platelets perfectly matched for HLA antigens. We have, therefore, investigated the effectiveness of platelets obtained from donors having lesser degrees of histocompatibility. In 421 transfusions administered to 59 alloimmunized patients who were refractory to "random donor" platelets, it was found that platelets mismatched for 1 or 2 "cross-reactive" HLA antigens were in most instances as effective in increasing circulating platelet levels as perfectly matched platelets. A significant number of patients also responded to platelets from donors selectively mismatched for non-cross-reactive HLA antigens. The latter group had a significantly reduced frequency of the antigen HLA-A2 (13%) in comparison to the total patient population (49%). Use of donors whose HLA antigens are serologically cross-reactive with those of alloimmunized patients provides approximately 10 times as many prospective donors as does selection based on matching for HLA and simplifies the procurement of hemostatically effective platelets for such patients.

Blood Platelets↗