Fibulin-4 is a target of autoimmunity predominantly in patients with osteoarthritis.

Abstract

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.

• Authors: Yang Xiang, Taichi Sekine, Hiroshi Nakamura, Shinobu Imajoh-Ohmi, Hiroyuki Fukuda, Kazuo Yudoh, Kayo Masuko-Hongo, Kusuki Nishioka, Tomohiro Kato
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 176 Issue 5 Pg. 3196-204 (Mar 01 2006) ISSN: 0022-1767 [Print] United States
• PMID: 16493080 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantigens
• EFEMP2 protein, human
• Extracellular Matrix Proteins
• Immunoglobulin G
• Myelin Basic Protein
• Recombinant Fusion Proteins

Topics

• Adult
• Aged
• Aged, 80 and over
• Amino Acid Sequence
• Animals
• Arthritis, Rheumatoid (immunology)
• Autoantigens (administration & dosage, biosynthesis)
• Chondrocytes (metabolism)
• Extracellular Matrix Proteins (administration & dosage, biosynthesis, immunology)
• Female
• Humans
• Immunoglobulin G (biosynthesis, blood)
• Lupus Erythematosus, Systemic (immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Mice, Inbred ICR
• Middle Aged
• Molecular Sequence Data
• Myelin Basic Protein (genetics, immunology)
• Osteoarthritis (blood, immunology)
• Recombinant Fusion Proteins (administration & dosage, genetics, immunology)
• Scleroderma, Systemic (immunology)
• Synovitis (immunology)