EXTENDED REPORT

A longitudinal study on an autoimmune murine model of ankylosing spondylitis

T Bárdos^1,2, Z Szabó^1,3, M Czipri^1,2, C Vermes^1,2, M Tunyogi-Csapó^1,2, R M Urban¹, K Mikecz^1,4,5, T T Glant^1,4,6

¹ Section of Molecular Medicine, Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, USA
² Department of Orthopaedic Surgery, University of Pécs, Pécs, Hungary
³ Department of Internal Medicine 3, University of Debrecen, Hungary
⁴ Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA
⁵ Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, USA
⁶ Internal Medicine (Section of Rheumatology), Rush University Medical Center, Chicago, IL 60612, USA

Correspondence to:
Dr T T Glant
Department of Orthopedic Surgery, Rush University Medical Center, Cohn Research Building, Room 708, 1735 W Harrison Street, Chicago, IL 60612, USA; tglant{at}rush.edu

Background: Proteoglycan aggrecan (PG)-induced arthritis (PGIA) is the only systemic autoimmune murine model which affects the axial skeleton, but no studies have been performed characterising the progression of spine involvement.

Objectives: To follow pathological events in experimental spondylitis, and underline its clinical, radiographic, and histological similarities to human ankylosing spondylitis (AS); and to determine whether the spondyloarthropathy is a shared phenomenon with PGIA, or an "independent" disease.

Methods: Arthritis/spondylitis susceptible BALB/c and resistant DBA/2 mice, and their F1 and F2 hybrids were immunised with cartilage PG, and radiographic and histological studies were performed before onset and weekly during the progression of spondylitis.

Results: About 70% of the PG immunised BALB/c mice develop spondyloarthropathy (proteoglycan-induced spondylitis (PGISp), and the progression of the disease is very similar to human AS. It begins with inflammation in the sacroiliac joints and with enthesitis, and then progresses upwards, affecting multiple intervertebral disks. In F2 hybrids of arthritis/spondylitis susceptible BALB/c and resistant DBA/2 mice the incidence of arthritis was 43.5%, whereas the incidence of spondylitis was >60%. Some arthritic F2 hybrid mice had no spondylitis, whereas others developed spondylitis in the absence of peripheral arthritis.

Conclusions: The PGISp model provides a valuable tool for studying autoimmune reactions in spondylitis, and identifying genetic loci associated with spondyloarthropathy.

Abbreviations: AS, ankylosing spondylitis; IVD, intervertebral disk; PG, proteoglycan aggrecan; PGIA, PG-induced arthritis; PGISp, PG-induced spondylitis; SpA, spondyloarthropathy

Keywords: animal model; ankylosing spondylitis; autoimmunity; proteoglycan aggrecan; mouse

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