Collagen type II-specific monoclonal antibody-induced arthritis in mice: description of the disease and the influence of age, sex, and genes.
Transfer of collagen type II (CII)-specific monoclonal antibodies induces an acute form of arthritis (collagen type II antibody-induced arthritis, CAIA) in naïve mice. Arthritis was induced using a pair of monoclonal antibodies M2139 and CIIC1, binding to J1 and C1(I) epitopes of CII, respectively. Thereafter, lipopolysaccharide injection was used to increase the incidence and severity of the disease. This model was used to investigate the effect of genes, age, and sex as well as effector cells in the end-stage effector phase of arthritis pathogenesis. Injection of a single monoclonal antibody induced arthritis only after lipopolysaccharide stimulation. CAIA showed differences in disease penetration among the susceptible strains indicating the importance of non-major histocompatibility complex genes on the antibody effector pathway. B-cell-deficient mice were susceptible to CAIA and in some genetic backgrounds B-cell deficiency leads to enhanced arthritis. Histology of the affected paws revealed massive infiltrations of neutrophils along with bone and cartilage erosion, pannus formation, and fibrin deposition. Depletion of neutrophils significantly reduced the incidence and severity of the disease. CAIA susceptibility increased with age. Males were more susceptible than females and estrogen treatment decreased the development of arthritis. We conclude that CAIA is an acute arthritis triggered by antibody binding and neutrophils bypassing immune activation but with many characteristics in common with collagen-induced arthritis.
Nandakumar
Kutty Selva
KS
Section for Medical Inflammation Research, I-11 BMC, Lund University, 22184 Lund, Sweden. nan@inflam.lu.se
Svensson
Lars
L
Holmdahl
Rikard
R
D000367:Age Factors; D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D024043:Collagen Type II / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D007114:Immunization; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D012737:Sex Factors
D000911:Antibodies, Monoclonal; D024043:Collagen Type II