Characterization of microbial deposition and immune response at the basement membrane and methods relating thereto

Abstract

Methods for diagnosing a systemic or autoimmune disorder and methods for treating the same by inducing the production of or otherwise providing an autoantibody that recognizes a skin basement membrane component.

Description

[0001] This application is based on and claims priority to U.S. Provisional Application Serial No. 60 / 183,647, filed Feb. 18, 2000, herein incorporated by reference in its entirety.[0002] The present invention pertains to the characterization of microbial deposition and immune response at the basement membrane of the skin and to methods relating to such characterization. In a preferred embodiment, an autoimmune response at the basement membrane in the skin of a subject has been characterized.1 Table of Abbreviations BMZ basement membrane zone DAKO LSAB .RTM. DAKO linked streptavidin biotin amplification and detection kit ELISA enzyme-linked immunosorbant assay IFN interferon IL interleukin IgA immunoglobulin class A IgG immunoglobulin class G MHC major histocompatability complex HLA human leukocyte antigen SPE Streptococcal pyrogenic exotoxin V.beta. T cell receptor V.beta.[0003] Psoriasis is a cutaneous inflammatory disorder characterized by epidermal keratinocyte hyperproliferatio...

AI Technical Summary

Benefits of technology

[0042] The use of a molecular cloning approach to generate antibodies, particularly monoclonal antibodies, and more particularly single chain monoclonal antibodies, are also provided. The production of single chain antibodies has been described in the art. See, e.g., U.S. Pat. No. 5,260,203. For this approach, combinatorial immunoglobulin phagemid libraries are prepared from RNA isolated from the spleen of the immunized animal, and phagemids expressing appropriate antibodies are selected by panning on a tissue of interest. The advantages of this approach over conventional hybridoma techniques are that approximately 10.sup.4 times as many antibodies can be produced and screened in a single experiment, and that new specificities are generated by heavy (H) and light (L) chain combinations in a single chain, which further increases the chance of finding appropriate antibodies. Thus, an antibody of the present invention, or a "derivative" of an antibody of the present invention, can optimally comprise a single polypeptide chain binding molecule which has binding specificity and affinity substantially similar to the binding specificity and affinity of the light and heavy chain aggregate variable region of an antibody described herein.

[0084] The invention provides compositions which enhance the immunocompetence of the host individual. The therapeutic compositions of the present invention have the capacity to prevent the onset and progression of disorders such as systemic infection by a pathogen, an autoimmune disorder, or a disorder associated with deposition of immune complexes at a BMZ. Preferably, the therapeutic composition comprises a BMZ antigen or an antibody that recognizes a BMZ component.

Problems solved by technology

Yet a model, and hence a therapy, that encompasses most, if not all, observations related to psoriasis remains undisclosed and unavailable in the art.

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