Relapsing polychondritis, induced in mice with matrilin 1, is an antibody- and complement-dependent disease

• Relapsing polychondritis is an autoimmune disease that affects cartilage in the ear, nose, and respiratory tract. A pathogenic immune response has been proposed and antibodies to several cartilage proteins are detected in sera from these patients. To investigate the role of the humoral immune response in relapsing polychondritis, we used the matrilin-1-induced relapsing polychondritis model. Mice deficient of B cells (muMT) and mice congenic at the complement factor 5, were immunized with matrilin-1, a cartilage-specific protein mainly detected in the tracheal cartilage. To investigate the binding properties and tissue selection of matrilin-1-specific antibodies we produced matrilin-1-specific B-cell hybridomas. Although 83% of the micro MT heterozygous mice developed respiratory distress and erosive chondritis in the respiratory tract, none of the B-cell-deficient mice were susceptible to disease. In addition, we show that complement factor 5 is important for the induction of matrilin-1-induced relapsing polychondritis. Monoclonal matrilin-1-specific antibodies injected into neonatal mice bound specifically to cartilage of the respiratory tract and adult B-cell-deficient mice injected with the same antibodies developed erosive chondritis in the respiratory tract. We conclude that relapsing polychondritis can be mediated by a pathway involving tissue-specific antibodies and complement activation.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Keyword

Animals

Animals

Newborn

*Antibodies

Autoimmune Diseases/immunology/pathology

B-Lymphocytes/*immunology

Cartilage/immunology/pathology

Complement C5/*immunology

Disease Models

Animal

Enzyme-Linked Immunosorbent Assay

Extracellular Matrix Proteins/*immunology/toxicity

Glycoproteins/*immunology/toxicity

Hybridomas

Matrilin Proteins

Mice

Mice

Congenic

Polychondritis

Relapsing/chemically induced/*immunology

Respiratory System/immunology

collagen-induced arthritis

cartilage matrix protein

ii collagen

rheumatoid-arthritis

monoclonal-antibodies

auricular chondritis

autoimmune-disease

experimental-model

develop

autoantibodies

Publication and Content Type

ref (subject category)

art (subject category)