The structure of human lupus anti-DNA antibodies

Methods : a Companion to Methods in Enzymology
M Zouali

Abstract

B-cell hyperactivity and production of pathogenic autoantibodies are the main immunological events in the pathogenesis of the human autoimmune disease systemic lupus erythematosus. One approach to studying the pathogenesis of this disease and to understanding how the autoantibody response is initiated and sustained has been to analyze the variable genes expressed by antibodies that have the hallmarks of the disease-causing subset of pathogenic autoantibodies. Such studies have provided important clues. Quantitation of this repertoire revealed the presence of a specific expansion of IgG clonotypes that impart reactivity with disease-related autoantigens. The sequences of the genes encoding autoantibodies derived from these patients and expressing nephritogenic idiotopes (present in immune complexes and renal eluates of subjects with active disease) show features of molecular diversification with a high rate of replacement/silent mutations and clustering of the mutations in the hypervariable regions. These characteristics imply that a pure polyclonal B-cell activation process cannot be the only mechanism responsible for autoantibody production. More likely, an antigen drive plays a role in generation of pathogenic autoantibodies....Continue Reading

Citations

May 8, 1998·The New England Journal of Medicine·B H Hahn
May 16, 2002·Molecular Immunology·Moncef Zouali
Feb 28, 2003·Clinical and Experimental Immunology·H AhsanR Ali
Apr 8, 2009·Health Care for Women International·Cindy Mendelson
Apr 16, 2013·Biochemistry. Biokhimii︠a︡·V N BunevaG A Nevinsky

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