Implication of cartilage intermediate layer protein in cartilage destruction in subsets of patients with osteoarthritis and rheumatoid arthritis.
OBJECTIVE
To investigate whether cartilage intermediate layer protein (CILP), a protein recently cloned from human articular cartilage, is recognized as an autoantigen in patients with osteoarthritis (OA) and rheumatoid arthritis (RA), and whether the immune response against CILP is involved in disease pathogenesis.


METHODS
Recombinant fusion proteins, which contain the first half (C1), second half (C2), or 3 fragments within the C2 region (designated C2F1, C2F2, and C2F3) of the non-porcine nucleotide pyrophosphohydrolase-homologous region of CILP, were prepared using Escherichia coli. Autoantibodies to these proteins in serum samples from patients with OA or RA and from age-matched healthy individuals were detected by enzyme-linked immunosorbent assay and Western blotting. In addition, mice were immunized with a mixture of the C1 and C2 fusion proteins to assess the arthrogenicity of CILP.


RESULTS
Production of antibodies to the C2 region was detected in 10.5% (11 of 105) of the tested OA patients and in 8.0% (7 of 88) of the tested RA patients, although antibodies to the C1 region were rarely detected in either patient group. All C2F1, C2F2, and C2F3 fragments were found to carry autoepitopes. The C2F2 fusion protein was recognized most frequently in the tested OA patients, whereas the C2F3 fusion protein was dominantly recognized in the tested RA patients. All 4 mice strains, DBA/1J, ICR, C57BL/6, and BALB/c, immunized with the CILP fusion proteins developed chronic arthritis; in particular, the ICR mice developed polyarthritis that was characterized by infiltration of mononuclear cells in the synovium and exfoliation of the surface of cartilage.


CONCLUSIONS
The immune response to CILP may play a role in the pathogenesis of inflammatory joint destruction. Our results support the role of an immune-mediated process in the joint destruction present in chronic arthropathies such as OA and RA. The results suggest that suppression of immune responses to various components of the cartilage, such as CILP, might be therapeutically beneficial in these chronic arthropathies.
Tsuruha
J
J
St. Marianna University School of Medicine, Kawasaki, Japan.
Masuko-Hongo
K
K
Kato
T
T
Sakata
M
M
Nakamura
H
H
Nishioka
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000276:immunology / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D002358:Cartilage, Articular / Q000276:immunology* / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007596:Joints / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology* / Q000473:pathology; D011755:Pyrophosphatases; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D011993:Recombinant Fusion Proteins; C114607:CILP protein, human; D011755:Pyrophosphatases