Serum Antibodies Against Intact Human Collagen IX Are Elevated at Onset of Rheumatoid Arthritis But Are Not Related to Development of Erosions

JUHA JÄÄLINOJA, MARTTI NISSILÄ, MARKKU J. KAUPPI, MARKKU HAKALA, KARI LAIHO, RIITTA KARTTUNEN, SOHVI HÖRKKÖ, and LEENA ALA-KOKKO

ABSTRACT.

Objective. To measure the presence of autoantibodies binding to intact human recombinant collagen IX and assess their usefulness as a diagnostic marker and an indicator of disease activity in rheumatoid arthritis (RA).

Methods. Recombinant human full-length collagen IX (rCIX) was produced in a baculovirus expression system and purified for use in ELISA developed to detect antibodies to native and denatured collagen IX. Fifty-three patients with recent-onset rheumatoid factor-seropositive RA were analyzed for the presence of rCIX antibodies of the IgG type at the time of initial diagnosis and after 3, 6, 12, and 24 months of followup. The RA sera were accompanied by 30 controls. Associations were determined between patients' antibody titers, development of erosions in the hands and feet, and various clinical and laboratory markers.

Results. Serum antibody levels among patients with RA at time of diagnosis were 1.78 times higher against native rCIX (p < 0.001) and 1.71 times higher against denatured rCIX (p < 0.001) than in the controls, and they remained high during the followup. No correlation was seen between antibody levels and clinical and laboratory findings.

Conclusion. Our data show that patients with recent-onset RA have significantly elevated levels of autoantibodies to human rCIX. These autoantibodies were observed already at the early stages of the disease, which may reflect their diagnostic potential in RA. (J Rheumatol First Release Mar 15 2008)

Key Indexing Terms:

COLLAGEN IX
RHEUMATOID ARTHRITIS
AUTOANTIBODY
DIAGNOSIS
ENZYME LINKED IMMUNOSORBENT ASSAY

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From the Collagen Research Unit, Biocenter Oulu; Departments of Medical Biochemistry and Molecular Biology, Medical Microbiology, and Pharmacology and Toxicology, University of Oulu, Oulu; Rheumatism Foundation Hospital, Heinola; Department of Musculoskeletal Medicine and Rehabilitation, Medical School, University of Tampere, Tampere; Kanta-Häme Central Hospital, Hämeenlinna, Finland; and Connective Tissue Gene Tests, Allentown, Pennsylvania, USA.

Supported by the Finnish Rheumatism Foundation.

J. Jäälinoja, MSc, Collagen Research Unit, Biocenter Oulu and Department of Medical Biochemistry and Molecular Biology; S. Hörkkö, MD, PhD, Department of Pharmacology and Toxicology, University of Oulu; M. Nissilä, MD, PhD; M.J. Kauppi, MD, PhD, Rheumatism Foundation Hospital; M. Hakala, MD, Professor; K. Laiho, MD, PhD, Rheumatism Foundation Hospital, and Department of Musculoskeletal Medicine and Rehabilitation, Medical School, University of Tampere; R. Karttunen, MD, PhD, Kanta-Häme Central Hospital, and Department of Medical Microbiology, University of Oulu; L. Ala-Kokko, MD, PhD, Professor, Collagen Research Unit, Biocenter Oulu and Department of Medical Biochemistry and Molecular Biology, University of Oulu, and Connective Tissue Gene Tests.

Address reprint requests to Dr. L. Ala-Kokko, Connective Tissue Gene Tests, 905 Harrison Street, Suite 134, Allentown, PA 18103, USA. E-mail: leena.ala-kokko@oulu.fi

Accepted for publication December 5, 2007.