Fibulin-4 is a target of autoimmunity predominantly in patients with osteoarthritis.
Autoimmunity to chondrocyte-producing proteins has been reported in patients with osteoarthritis (OA) as well as in those with rheumatoid arthritis (RA). To answer whether or not OA-specific autoimmunity exist, we performed screening of chondrocyte-producing autoantigens by two-dimensional electrophoresis and Western blotting with each of 20 OA and 20 RA serum samples. We identified an apparently OA-specific autoantigen spot with a molecular mass of 52 kDa and a Isoelectric point of 4.1 as fibulin-4 by mass fingerprinting. By preparing recombinant proteins of fibulin-4, we determined prevalence of the autoantibodies to fibulin-4 in 92 patients with OA, 67 patients with RA, 40 patients with systemic lupus erythematosus, and 43 patients with systemic scleroderma. As a result, the IgG type anti-fibulin-4 autoantibodies were detected in 23.9% of sera from patients with OA, in 8.9% of sera from patients with RA, in 2.5% of sera from patients with systemic lupus erythematosus, and in 9.3% of sera from patients with systemic scleroderma. Furthermore, we immunized DBA/1J, ICR, BALB/c, and C57BL/6 mice with the recombinant fibulin-4 proteins to investigate arthritogenecity of fibulin-4. As a result, mild synovitis was detected in all of the four strains. In addition, we demonstrated expression of fibulin-4 in chondrocytes at both mRNA and protein levels in vivo and in vitro by RT-PCR, Western blotting, and immunohistochemistry. Taken together, fibulin-4, expressed in chondrocytes and recognized as an autoantigen mainly in OA rather than in RA, may play pathogenic roles in OA.
Xiang
Yang
Y
Department of Bioregulation and Proteomics, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
Sekine
Taichi
T
Nakamura
Hiroshi
H
Imajoh-Ohmi
Shinobu
S
Fukuda
Hiroyuki
H
Yudoh
Kazuo
K
Masuko-Hongo
Kayo
K
Nishioka
Kusuki
K
Kato
Tomohiro
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001324:Autoantigens / Q000008:administration & dosage / Q000096:biosynthesis*; D019902:Chondrocytes / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000008:administration & dosage* / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D008875:Middle Aged; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000235:genetics / Q000276:immunology; D010003:Osteoarthritis / Q000097:blood / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D012595:Scleroderma, Systemic / Q000276:immunology; D013585:Synovitis / Q000276:immunology
D001324:Autoantigens; C403672:EFEMP2 protein, human; D016326:Extracellular Matrix Proteins; D007074:Immunoglobulin G; D004676:Myelin Basic Protein; D011993:Recombinant Fusion Proteins