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A H Lazarus

Publications and source records attributed to A H Lazarus.

40 records · Page 3Linked to original sources
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Comparison of platelet immunity in patients with SLE and with ITP.

Idiopathic thrombocytopenic purpura (ITP) is characterized by the development of a specific anti-platelet autoantibody immune response mediating the development of thrombocytopenia. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of a wide variety of autoantibodies. In 15-20% of SLE cases, patients develop thrombocytopenia which appears to be autoimmune in nature (SLE-TP). To better understand the pathogenesis of the thrombocytopenia associated with SLE, we investigated the overlapping platelet and cellular immune features between SLE and ITP. Thirty-one patients with SLE, eight with SLE-TP, and 17 with ITP, were studied and compared to 60 healthy controls. We evaluated platelet-associated IgG, platelet microparticles, reticulated platelets, platelet HLA-DR expression, in vivo cytokine levels, lymphocyte proliferation, and the T lymphocyte anti-platelet immune response in these patients. Patients with SLE-TP and those with ITP had increased platelet-associated IgG, an increased percentage of platelet microparticles, a higher percentage of reticulated platelets and larger platelets, suggesting antibody-mediated platelet destruction and increased platelet production. More than 50% of patients with ITP had increased HLA-DR on their platelet surface whereas subjects with SLE-TP did not. Analysis of serum cytokines demonstrated increased levels of IL-10, IL-15 and TNF-alpha in patients with SLE, but in those with ITP, only increased levels of IL-15 were seen, no increases in any of these cytokines were observed in patients with in SLE-TP. The ability of lymphocytes to proliferate in response to phorbol myristate acetate (PMA) stimulation was increased in SLE-TP, but was normal in both SLE and ITP. Lymphocytes from subjects with ITP displayed an increased ability to proliferate on exposure to platelets, in contrast, those with SLE-TP did not. While the number of subjects evaluated with SLE-TP was small, these data reveal a number of differences in the immunopathogenesis between SLE-TP and ITP.

Adult↗
PubMedDate not supplied

Induction of a secondary human anti-HLA alloimmune response in severe combined immunodeficient mice engrafted with human lymphocytes.

BACKGROUND: Experimental manipulation of transfusion-induced alloimmunization is limited in humans by ethical considerations. Conversely, studies of alloimmunization in animal models may not reflect the human immune system closely enough to be of optimal benefit. The development of an in vivo model of human alloimmunization that is amenable to experimental manipulation is thus desirable. STUDY DESIGN AND METHODS: An in vivo model of human alloimmunization was evaluated by using mice with severe combined immunodeficiency (SCID). SCID mice underwent gamma-radiation (200 cGy) and received an intraperitoneal injection of human peripheral blood lymphocytes (PBLs) from donors immunized to HLA antigens by prior pregnancy (reconstitution). These Hu [human]-PBL-SCID mice were then challenged with HLA-mismatched PBLs. Alloantibodies were evaluated by flow cytometry and a standard two-stage microlymphocytotoxicity assay. RESULTS: Hu-PBL-SCID mice (n = 22) that were challenged with PBLs expressing the HLA antigens to which the donors had previously been immunized, made significantly more IgM and IgG alloantibodies than did the unchallenged mice. Responses were measurable by 1 week after reconstitution and challenge. Prior treatment of SCID mice with anti-asialo GM1, which depletes murine natural killer cells and macrophages, further increased the alloantibody response of challenged mice. The human alloantibodies generated were specific to the challenge HLA antigens as assessed by microlymphocytotoxicity assay. CONCLUSION: Hu-PBL-SCID mice are a useful model system in which to study and manipulate the induction of secondary human alloimmune responses against cellular HLA class I antigens. This model will be valuable for testing the in vivo effect of novel immunotherapies on the inhibition of the human alloantibody response.

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