Lymphocyte Antibody

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K. Gelsthorpe - One of the best experts on this subject based on the ideXlab platform.

R.w. Doughty - One of the best experts on this subject based on the ideXlab platform.

Robert A Horlick - One of the best experts on this subject based on the ideXlab platform.

  • Mammalian cell display and somatic hypermutation in vitro for human Antibody discovery.
    Current drug discovery technologies, 2014
    Co-Authors: David J. King, Marilyn R Kehry, Peter M. Bowers, Robert A Horlick
    Abstract:

    Human therapeutic Antibody discovery has utilized a variety of systems, from in vivo immunization of human immunoglobulin-expressing mice, to in vitro display of Antibody libraries. Of the in vitro Antibody display technologies, mammalian cell display provides a number of advantages with the ability to co-select immunoglobulin molecules for high expression level in mammalian cells, native folding, and biophysical properties appropriate for drug development. Mammalian cell display has been achieved using either transient or stable expression systems, using a number of alternate transmembrane domains to present Antibody on the cell surface. The unique capability of mammalian cells to present IgG in its fully post-translationally modified format also allows selection of antibodies for functional properties. One limitation of mammalian cell based systems, however, has been the smaller library size that can be presented compared to phage display approaches. Until recently, this has necessitated the use of libraries biased toward a particular antigen, such as libraries derived from immunized donors, to achieve success. An alternative approach has now been developed which recapitulates key aspects of the in vivo immune system through reproducing somatic hypermutation (SHM) in vitro. Libraries representing a naïve human B Lymphocyte Antibody repertoire are created by PCR amplification of the rearranged (D)J segments of heavy and light chain variable regions from human donors and incorporating the resulting sequence diversity into panels of human germline VH and VL genes. The resulting antibodies are presented as full length IgG on the surface of HEK293 cells. After isolation of antibodies binding to individual target antigens, subsequent affinity maturation using in vitro SHM is induced by expression of activation-induced cytidine deaminase (AID). Selection of antibodies from naïve fully human libraries using mammalian cell display coupled with in vitro SHM is an efficient methodology for the generation of high affinity human antibodies with excellent properties for drug development.

Jean-françois Yale - One of the best experts on this subject based on the ideXlab platform.

  • Predictive Value of Lymphocyte Antibodies for the Appearance of Diabetes in BB Rats
    Diabetes, 1994
    Co-Authors: Sylvie Bertrand, Claire Vigeant, Jean-françois Yale
    Abstract:

    Lymphocyte antibodies have been described in autoimmune disorders, including insulin-dependent diabetes mellitus (IDDM). We have developed a quantitative method to measure autoantibodies directed against T-Lymphocytes, based on two-color fluorescence labeling of Wistar mononuclear cells and analysis of fluorescence by flow cytometry. The Lymphocyte Antibody levels were determined retrospectively in the serum of 73 BB and 18 Wistar rats. We demonstrated the binding of the Lymphocyte autoantibodies of both CD4 + and CD8 + T-cells. Lymphocyte antibodies were present in 90% of the BB rats at diabetes onset, compared with 11% of the Wistar rats. At 75 days of age, 83% of the BB rats, which later became diabetic, were positive for the Lymphocyte antibodies, compared with 15% of their litter mates who maintained a normal glucose tolerance. In all cases, the antibodies were of the immunoglobulin M isotype. We conclude that Lymphocyte antibodies are present before diabetes onset and, using this method, that their presence can predict the development of diabetes with a sensitivity of 83% and a specificity of 85% in BB rats.

Ron Shapiro - One of the best experts on this subject based on the ideXlab platform.

  • reversal of steroid and anti Lymphocyte Antibody resistant rejection using intravenous immunoglobulin ivig in renal transplant recipients
    Transplantation, 2001
    Co-Authors: Patrick Luke, Thomas R. Hakala, Velma P Scantlebury, Mark L Jordan, Carlos Vivas, Ashok Jain, Alka Somani, Sheila Fedorek, Parmjeet Randhawa, Ron Shapiro
    Abstract:

    BACKGROUND: Despite the recent advances in immunosuppression, steroid-resistant rejection remains a difficult problem in renal transplant recipients. METHODS: We reviewed our experience with i.v. immunoglobulin (IVIG) in the treatment of steroid- and antiLymphocyte Antibody-resistant rejection in renal transplant patients. Between September 1996 and March 1999, 17 patients were treated with IVIG to reverse steroid- or antiLymphocyte Antibody-resistant rejection. A total of 2 g/kg of IVIG was administered to patients during each treatment course. RESULTS: With a mean follow-up of 21.5+/-9.5 months from the time of IVIG administration, patient and graft survival rates were 94% (16/17) and 71% (12/17), respectively. The baseline mean serum creatinine level prior to rejection was 2.2+/-0.7 mg/dl and peaked at 3.3+/-1.1 mg/dl at the time of the diagnosis of refractory rejection. IVIG therapy was associated with a fall in the mean creatinine to 2.8+/-1.1 mg/dl. The most recent serum creatinine in patients with functioning grafts was 2.8+/-1.6 mg/dl. In 82% of allograft biopsies after IVIG, reversal or reduction in the severity of rejection was demonstrated. In addition, IVIG therapy rescued three of four patients with antiLymphocyte Antibody-resistant rejection. CONCLUSIONS: IVIG rescue therapy for steroid- or antiLymphocyte Antibody-resistant rejection is associated with resolution or improvement of rejection severity, stable renal function, and reasonable graft survival.