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E Mickelson

Publications and source records attributed to E Mickelson.

49 records · Page 3Linked to original sources

HLA-Dw"SHY": a new lymphocyte defined specificity associated with HLA-DRw10.

HLA-DRw10 is a relatively new class II serologically-defined alloantigen first described in the 8th International Histocompatibility Workshop. To date the HLA-Dw related to the DRw10 specificity has not been detected. We have studied a Jewish family ("SHY") of Yemenite origin, in which the parents are first cousins who share one HLA haplotype: A29,Cw2,B7,BfF,DRw10,GL02. Two of the offspring in this family are homozygous for this haplotype. MLC family study confirmed that each of the two individuals was homozygous for HLA-Dw. No currently defined HLA-Dw specificity could be assigned to "SHY" using a selected panel of Caucasoid and local HTcs. HLA-Dw"SHY" was shown to segregate with DRw10 positive/Dw blank haplotypes in two families and in 64% (7/11) of DRw10 positive unrelated positive/Dw blank haplotypes in two families and in 64% (7/11) of DRw10 positive unrelated individuals. HTC"SHY" thus expresses the first HLA-Dw specificity associated with DRw10.

Epitopes↗

HLA-DR2 and DR4 further defined by two new HLA-D specificities (HTC) derived from Israeli Jewish donors: comparative study in Caucasian, Korean, Eskimo and Israeli populations.

Two newly-identified HLA-D antigens were characterized by testing selected homozygous typing cells (HTC) against responder panels derived from Caucasian, Korean, Alaskan Eskimo and Israeli Jewish populations. The first specificity, defined by typing cell "AZH", is associated with DR2 haplotypes and is detected primarily in Israelis. The second specificity, defined by HTC "TAS", is associated with DR4 haplotypes and is detected with relatively high frequency in Koreans and Alaskan Eskimos. The data indicate that HTC-AZH and -TAS can be used to identify previously undefined splits or variants of lymphocyte-defined (LD) determinants associated with DR2 and DR4 haplotypes. Further, the study demonstrates the utility of comparative population analysis in identifying and characterizing alleles encoded by the HLA-D region and provides additional evidence of heterogeneity within the family of serologically-defined HLA-DR haplotypes.

HLA-DR Antigens↗

Specific HLA-DR4-associated histocompatibility molecules characterize patients with seropositive juvenile rheumatoid arthritis.

The structural and functional heterogeneity of HLA-DR4-associated specificities was investigated in patients with seropositive juvenile rheumatoid arthritis, a DR4-associated disease. Using a combination of HLA-D analysis by mixed lymphocyte culture and electrophoretic analysis of immunoprecipitated Ia molecules by two-dimensional polyacrylamide gels, we observed a surprisingly homogeneous pattern of HLA-D antigen expression. All patients expressed common structural products of the DR and DS loci, and 7/12 homozygous DR4 patients expressed a rare and subtle HLA-D heterozygous phenotype.

Arthritis, Juvenile↗

Electrophoretic analysis of human HLA-DR antigens from HLA-DR4 homozygous cell lines: correlation between beta-chain diversity and HLA-D.

Two-dimensional gel electrophoresis of immunoprecipitated human HLA-DR antigens from cells expressing the HLA-DR4 haplotype shows distinct clustering of beta-chain patterns. Six unique electrophoretic variants were observed among 17 HLA-DR4 homozygous cell lines (HCL) analyzed. These patterns correlate precisely with the HLA-D phenotype of the HCL donor as determined by reactivity in mixed lymphocyte culture. All DR4 HCL that belong to one of the well-defined HLA-D antigen groups (Dw4, Dw10, LD "40", LD "DYT", LD "KT2", or LD "TAS") have identical DR beta-chain patterns; DR4 HCL belonging to different HLA-D antigen groups do not. The concordance of the functional expression in mixed lymphocyte culture of a specific D phenotype with a distinct DR beta-chain pattern on gel analysis provides a direct structural basis for understanding the genetic control of HLA-D polymorphisms; HLA-D specificities as revealed by T-cell recognition in mixed lymphocyte culture thus might be accounted for by DR beta-chain polymorphisms. The extent of this beta-chain diversity within a single DR haplotype may aid in understanding variations in Ia-regulated functions, such as Ir gene control and certain disease susceptibilities.

B-Lymphocytes↗

Factors associated with graft rejection after HLA-identical marrow transplantation for aplastic anaemia.

One hundred and seventy-five consecutive patients with severe aplastic anaemia were given high-dose cyclophosphamide followed by marrow grafts from healthy, HLA-identical family members, and 168 lived long enough to show engraftment. In 38 patients the graft was rejected and 29 of these died. This analysis, using a binary logistic regression model, was aimed at identifying factors that predicted marrow graft rejection. Five factors correlated with graft rejection: (1) previous blood transfusion; (2) a positive relative response in mixed leucocyte culture indicating sensitization of patient against donor; (3) a low number of marrow cells used for transplantation; (4) marrow grafts from male donors; and (5) lack of infusion of viable donor buffy coat cells in addition to the marrow for transfused patients. The findings confirm the importance of transplanting early before transfusion and indicate that the greatest possible amount of donor marrow (supplemented by stem cells/lymphoid cells derived from the peripheral blood) should be obtained.

Anemia, Aplastic↗

Autologous marrow recovery and sensitization to non-HLA antigens after HLA-identical marrow transplantation for aplastic anemia.

One hundred seventy-five patients with severe aplastic anemia were treated by high-dose cyclophosphamide and HLA-A, -B, and -D-identical sibling marrow transplants. Thirty-eight patients rejected their grafts. Four of the 38 showed autologous marrow recovery as determined by blood genetic markers. The remarkable feature of one case following autologous marrow recovery was the presence of unidirectional proliferative and cytotoxic responses of circulating host lymphocytes to marrow donor lymphocytes in mixed lymphocyte culture and cell-mediated lympholysis. Presumably these responses were the result of in vivo sensitization to those non-HLA antigens for which donor and recipient differed.

Adolescent↗

Combined immunodeficiency and reticuloendotheliosis with eosinophilia.

A generalized erythematous scaly rash, alopecia, lympadenopathy, and hepatosplemonegaly developed in an infant girl during the first 6 weeks of life. Repeated bacterial and fungal infections, persistent diarrhea, and generalized wasting complicated the course of her illness, and death occurred at 5 1/2 months of age. Lymph node architecture was completely obliterated by histiocytes and eosinophils; no plasma cells or germinal centers were present. Both humoral and cellular immune systems were severely but not completely impaired. Familial reticuloendotheliosis with eosinophilia is, in some cases, associated with combined immune deficiency.

Antibody Formation↗

Mixed leukocyte reactivity and leukemia: study of identical siblings.

This report describes a search for tumor-specific transplantation antigens in man by testing four sets of identical siblings using the mixed leukocyte transformation reaction. In each case, one member of the set had acute leukemia in relapse. In no instance did the leukemic cells of the patient stimulate the cells of the normal twin, nor did cells from the normal twin stimulate cells from the leukemic patient. Possible explanations for the failure to detect a leukemia-associated antigen in these studies are discussed.

Antigens↗