Open AccessVery long charge runs in systemic lupus erythematosus-associated autoantigens.
Author(s) -
Volker Brendel,
Jan G. Dohlman,
B. Edwin Blaisdell,
Samuel Karlin
Publication year - 1991
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.88.4.1536
Subject(s) - autoantibody , anti nuclear antibody , cytoplasm , antigen , systemic lupus erythematosus , charge (physics) , immunology , antibody , biology , intracellular , lupus erythematosus , chemistry , microbiology and biotechnology , medicine , physics , pathology , disease , quantum mechanics
Systemic lupus erythematosus and other chronic systemic autoimmune diseases are associated with circulating autoantibodies reactive with a limited set of mostly nuclear proteins. Using rigorous statistical methods we have identified segments of highly significant charge concentration in the majority of the characteristic nuclear and cytoplasmic autoantigens. Extremely long runs of charged residues, including some sequences of greater than 20 consecutive charged residues (purely acidic or mixed basic and acidic), occur in about a third of these proteins, whereas equivalent runs are found in less than 3% of other mammalian proteins. The other sequences have less extreme charge clusters, the type and location of which are often conserved between several otherwise nonsimilar antigens. We propose that supercharged surfaces render the targeted host proteins strongly immunogenic and that antinuclear antibody profiles might result from chronic exposure to intracellular contents, possibly in conjunction with crossreactive viral products. The limited number of potential systemic autoantigens may partly be due to the rarity of requisite charge properties.