Analysis of human self-reactive antibody repertoires by quantitative immunoblotting.
We review the use of a quantitative immunoblotting technique to characterize human self-reactive antibody repertoires in health and disease. The interactions of plasma IgM and IgG with tissue extracts as sources of self-antigens were analyzed by quantitative immunoblotting. Data were compared by means of multiparametric statistical analysis. The data summarized here demonstrate that natural self-reactive antibody repertoires of healthy individuals are restricted to a limited subset of immunodominant autoantigens that is selected early in development, and remains conserved between individuals through ageing. The selection of human natural self-reactive IgG antibody repertoires requires normal T-/B-cell interactions. The immunoblotting assay has the potential to distinguish between autoimmune diseases with organ-related oligoclonal expansion of self-reactive clones and those characterized by broad alterations of immunoregulation. However, organ-specific autoimmune diseases may be characterized by altered patterns of antibody repertoires unrelated to the target organ. The assay also revealed an unexpected defect in the regulatory function of self-reactive IgM on the expression of self-reactive IgG repertoires in several systemic and organ-specific autoimmune diseases. The results are discussed in the light of our current understanding of the processes of selection of self-reactive B-cells and the pathophysiology of autoimmunity.
Stahl
D
D
INSERM (Institut National de la Santé et de la Recherche Médicale) U430 and Université Pierre et Marie Curie, Hôpital Broussais, Paris, France. stahld@uni-muenster.de
Lacroix-Desmazes
S
S
Mouthon
L
L
Kaveri
S V
SV
Kazatchkine
M D
MD
D001323:Autoantibodies / Q000276:immunology / Q000302:isolation & purification*; D001327:Autoimmune Diseases / Q000276:immunology; D006801:Humans; D015151:Immunoblotting / Q000379:methods*; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007136:Immunoglobulins / Q000276:immunology*; D008258:Waldenstrom Macroglobulinemia / Q000276:immunology
D001323:Autoantibodies; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins