Antibody-induced arthritis: disease mechanisms and genes involved at the effector phase of arthritis.
During the development of rheumatoid arthritis (RA) autoantibodies to IgG-Fc, citrullinated proteins, collagen type II (CII), glucose 6 phosphoisomerase (G6PI) and some other self-antigens appear. Of these, a pathogenic effect of the anti-CII and anti-G6PI antibodies is well demonstrated using animal models. These new antibody mediated arthritis models have proven to be very useful for studies involved in understanding the molecular pathways of the induction of arthritis in joints. Both the complement and FcgammaR systems have been found to play essential roles. Neutrophils and macrophages are important inflammatory cells and the secretion of tumour necrosis factor-alpha and IL-1beta is pathogenic. The identification of the genetic polymorphisms predisposing to arthritis is important for understanding the complexity of arthritis. Disease mechanisms and gene regions studied using the two antibody-induced arthritis mouse models (collagen antibody-induced arthritis and serum transfer-induced arthritis) are compared and discussed for their relevance in RA pathogenesis.
Nandakumar
Kutty Selva
KS
Medical Inflammation Research, Lund University, Lund 22184, Sweden. nan@med.lu.se
Holmdahl
Rikard
R
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000378:metabolism; D000918:Antibody Specificity; D001169:Arthritis, Experimental; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005956:Glucose-6-Phosphate Isomerase / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D012217:Rheumatoid Factor / Q000378:metabolism*; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D005819:Genetic Markers; D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha; D012217:Rheumatoid Factor; D005956:Glucose-6-Phosphate Isomerase