The occurrence of autoantibodies to matrilin 1 reflects a tissue-specific response to cartilage of the respiratory tract in patients with relapsing polychondritis

Objective. Relapsing polychondritis (RP) is an inflammatory disease that ma inly affects cartilage tissue in the auricle, nose, and lower respiratory t ract. When tracheolaryngeal cartilage is involved, the disease is occasiona lly fatal. Matrilin 1 is a cartilage-specific protein most prominently expr essed in tracheal cartilage, but not in joint cartilage. Immunization with the protein in rats and mice induces respiratory distress and nasal destruc tion, as seen in RP. We investigated the response to matrilin 1 and other c artilage proteins in sera from patients with RP, 4 additional groups of pat ients with other major connective tissue diseases, and healthy control subj ects. Methods. Sera were analyzed by enzyme-linked immunosorbent assay (ELISA) fo r antibody responses to matrilin 1, types II, IX, and XI collagen, and cart ilage oligomeric matrix protein (COMP). Titers above the mean + 3SD of cont rols were considered positive. Specificity of matrilin 1 recognition was fu rther investigated by the capacity of high-titer sera to block the binding of a matrilin 1-specific monoclonal antibody in inhibition ELISAs. In vivo reactivity and specificity were tested by injecting sera into neonatal mice , and antibody binding was detected by immunohistochemical staining. Results. Serum antibodies from RP patients bound tracheolaryngeal and nasal cartilage in vivo and inhibited the binding of anti-matrilin 1-specific mo noclonal antibodies. Thirteen of the 97 RP patients had increased titers of matrilin 1 antibody. Positive titers correlated with respiratory symptoms in 69% of the cases. Significant responses to type II collagen and COMP wer e also detected. Conclusion. Antibodies to matrilin 1 bind tracheolaryngeal cartilage in viv o and are correlated with an inflammatory attack on tracheolaryngeal cartil age that is often seen in RP.