Histological Patterns of Synovitis and Serum Chemokines in Patients with Rheumatoid Arthritis

PIOTR ADRIAN KLIMIUK, STANISLAW SIERAKOWSKI, ROBERT LATOSIEWICZ, JAN SKOWRONSKI, JACEK PRZEMYSLAW CYLWIK, BOHDAN CYLWIK, and JUSTYNA CHWIECKO

ABSTRACT.

Objective. Studies indicate the genetic, biological, and clinical heterogeneity of rheumatoid arthritis (RA). Recently the histological diversity of RA has been postulated. We investigated whether serum concentrations of interleukin 8 (IL-8), RANTES (regulated upon activation normal T cell expressed and secreted), and monocyte chemoattractant protein-1 (MCP-1) are correlated with histological appearance of the rheumatoid synovitis.

Methods. Using ELISA we assessed IL-8, RANTES, and MCP-1 concentrations in serum of 47 patients with RA and 30 patients with osteoarthritis (OA).

Results. Morphological analysis of synovial specimens distinguished 2 types of rheumatoid synovitis. Twenty-eight RA samples presented diffuse infiltrates of mononuclear cells with no specific microanatomical organization and were categorized as diffuse synovitis. In the remaining 19 specimens, classified as follicular synovitis, formation of lymphocytic follicles with germinal center-like structures was observed. Serum levels of studied chemokines were increased in patients with RA compared to the OA control group (p < 0.001 for all comparisons). Concentrations of IL-8, RANTES, and MCP-1 were highest in serum of RA patients with follicular synovitis in comparison with patients with diffuse synovitis (p < 0.01, p < 0.01, and p < 0.05, respectively) and could distinguish RA patients with these 2 histological disease patterns. Serum levels of chemokines correlated with markers of disease activity such as erythrocyte sedimentation rate, C-reactive protein concentrations, and Disease Activity Score.

Conclusion. Distinct histological variants of rheumatoid synovitis associated with different serum levels of IL-8, RANTES, and MCP-1 reflect clinical activity of the disease and confirm the concept of RA heterogeneity. (J Rheumatol 2005;32:1666-72)

Key Indexing Terms:

INTERLEUKIN 8
RANTES
MONOCYTE CHEMOATTRACTANT PROTEIN-1
RHEUMATOID ARTHRITIS
SYNOVITIS
HISTOLOGY

---

From the Department of Rheumatology and Internal Diseases, Department of Rehabilitation Medicine, Department of Orthopaedics and Traumatology, and Department of Clinical Pathology, Medical University of Bialystok, Bialystok, Poland.

P.A. Klimiuk, MD, PhD, Assistant; S. Sierakowski, MD, PhD, DSc (Med), Professor and Chair; J. Chwiecko, MA, PhD, Principal Technician, Department of Rheumatology and Internal Diseases; R. Latosiewicz, MD, PhD, Chair, Department of Rehabilitation Medicine; J. Skowronski, MD, PhD, Professor and Chair, Department of Orthopaedics and Traumatology; J.P. Cylwik, MD, Assistant; B. Cylwik, MD, PhD, Assistant, Department of Clinical Pathology.

Address reprint requests to Dr. P.A Klimiuk, Department of Rheumatology and Internal Diseases, Medical University of Bialystok, M.C. Sklodowskiej 24a, 15-276 Bialystok, Poland. E-mail: klimp@amb.edu.pl

Accepted for publication April 22, 2005.

---