The work will characterize pathogenic mechanisms of disease in patients with systemic lupus erythematosus (SLE). New knowledge will be sought on how immune complexes will deposit in tissues, using experimental animals. Previous studies have shown that patients with SLE have IgG in circulation that binds to Ckq in solid phase assays. Immunochemical techniques techniques will be used to determine if these molecules bind to Clq as antibodies or as small immune complexes. The isoelectric points of antibodies in large immune complexes of patients with SLE will be determined by isoelectric focusing and these findings will be related to the nature of renal disease of these patients. These studies will determine if charge-charge interactions contribute to glomerular deposition of immune complexes in patients with SLE. The nature and specificity of antibodies and antigens will be determined in serum immune complexes of patients with SLE. After evaluation of elution and detection methods with material from mouse models, the nature of antibodies and their specificity in immune material from mouse models, the nature of antibodies and their specificity in immune deposits at the dermal-epidermal junction of patients with SLE will be determined. In experimental animals mechanisms of immune complex deposition in glomeruli will be studied. The deposition in glomeruli of immune complexes with complement components will be tested. The contribution of positively charged regions of antigen molecules to deposition in glomeruli by charge-charge interaction will be investigated. The contribution of hypertension to mesangial deposition of immune complexes will be evaluated. The role of concentration dependent polymerization of macromolecules in deposition in glomerular mesangium will be examined with native and modified macromolecules for which polymerization will be characterized.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
Project #
Application #
Study Section
Pathology A Study Section (PTHA)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Washington
Schools of Medicine
United States
Zip Code
Mannik, Mart; Merrill, Cynthia E; Stamps, Louis D et al. (2003) Multiple autoantibodies form the glomerular immune deposits in patients with systemic lupus erythematosus. J Rheumatol 30:1495-504
Kohro-Kawata, Junko; Wener, Mark H; Mannik, Mart (2002) The effect of high salt concentration on detection of serum immune complexes and autoantibodies to C1q in patients with systemic lupus erythematosus. J Rheumatol 29:84-9
Mannik, M; Merrill, C E; Wener, M H (2000) Antibodies to human myeloperoxidase in glomerular immune deposits of systemic lupus erythematosus. Lupus 9:607-13
Mannik, M; Wener, M H (1997) Deposition of antibodies to the collagen-like region of C1q in renal glomeruli of patients with proliferative lupus glomerulonephritis. Arthritis Rheum 40:1504-11
Mannik, M (1996) Presence of covalent bonds between immune deposits and other macromolecules in murine renal glomeruli. Clin Exp Immunol 103:285-8
Gauthier, V J; Tyler, L N; Mannik, M (1996) Blood clearance kinetics and liver uptake of mononucleosomes in mice. J Immunol 156:1151-6
Uwatoko, S; Mannik, M; Oppliger, I R et al. (1995) C1q-binding immunoglobulin G in MRL/l mice consists of immune complexes containing antibodies to DNA. Clin Immunol Immunopathol 75:140-6
Mannik, M; Kobayashi, M; Alpers, C E et al. (1993) Antigens of varying size persist longer in subepithelial than in subendothelial immune deposits in murine glomeruli. J Immunol 150:2062-71
Uwatoko, S; Gauthier, V J; Mannik, M (1991) Autoantibodies to the collagen-like region of C1Q deposit in glomeruli via C1Q in immune deposits. Clin Immunol Immunopathol 61:268-73
Mannik, M; Person, R E (1991) New antigenic determinants revealed on human IgG by binding to immunoblotting membranes [corrected] J Immunol Methods 144:265-7

Showing the most recent 10 out of 21 publications