Anti-Tumor Necrosis Factor-a Response in Rheumatoid Arthritis Is Associated with an Increase in Serum Soluble CD30

ROBERTO GERLI, CLAUDIO LUNARDI, ELENA BARTOLONI BOCCI, FRANCESCA BOBBIO-PALLAVICINI, GIUSEPPE SCHILLACI, ROBERTO CAPORALI, ONELIA BISTONI, MATTEO PIRRO, COSTANTINO PITZALIS, and CARLOMAURIZIO MONTECUCCO

ABSTRACT.

Objective. Patients with rheumatoid arthritis (RA) display high serum concentrations of soluble CD30 (sCD30), which correlate with counter-regulatory activity of CD30+ T cells in the inflamed joint. To verify the contribution of this T cell subset to disease remission, sCD30 levels were analyzed longitudinally in patients with active RA following infliximab therapy.

Methods. Infliximab plus methotrexate were started in 39 patients with active RA, while 20 patients with inactive disease, controlled by stable doses of methotrexate, acted as controls. Serial evaluations of sCD30 concentrations and disease activity indexes were performed throughout 38 weeks.

Results. sCD30 levels were higher in patients than in healthy controls. Rapid infliximab-induced decrease in disease activity was associated with an overall increase of sCD30 levels. In contrast, levels remained stable in controls. An inverse correlation between sCD30 levels and Disease Activity Score 28 was observed from the 22nd week of infliximab treatment. Analysis of sCD30 levels according to American College of Rheumatology response showed, after an initial general enhancement of sCD30 concentrations, a persistent increase of sCD30 in responders, but not in nonresponders.

Conclusion. sCD30 serum levels are enhanced by tumor necrosis factor-a (TNF-a) blockade in patients with active RA and inversely correlated with disease activity, but only after some weeks of treatment. Of interest, a sustained increase of sCD30 is present only in subjects with evidence of persistent clinical response to anti-TNF-a. As sCD30 serum levels mirror antiinflammatory activity of joint T cells, the present data may suggest a role of synovial counter-regulatory CD30+ T cells in the induction of infliximab-mediated remission in RA. (First Release Dec 1 2007; J Rheumatol 2008;35:14-9)

Key Indexing Terms:

RHEUMATOID ARTHRITIS
ANTI-TUMOR NECROSIS FACTOR-a
CD30
INFLIXIMAB
T CELLS

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From the Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.

Drs. Pitzalis and Montecucco contributed equally to the design and performance of the study.

R. Gerli, MD; E. Bartoloni Bocci, MD; O. Bistoni, BSc, Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Perugia; C. Lunardi, MD, Department of Clinical and Experimental Medicine, University of Verona; F. Bobbio-Pallavicini, MD; R. Caporali, MD; C. Montecucco, MD, Rheumatology Unit, IRCCS Policlinico S. Matteo, University of Pavia; G. Schillaci, MD; M. Pirro, MD, Section of Internal Medicine, Angiology and Atherosclerosis Diseases, Department of Clinical and Experimental Medicine, University of Perugia; C. Pitzalis, MD, Rheumatology Unit, GKS School of Medicine, Guy's Campus, London, UK.

Address reprint requests to Prof. R. Gerli, Rheumatology Unit, Section of Internal Medicine and Oncological Sciences, Department of Clinical and Experimental Medicine, Policlinico Monteluce, I-06122 Perugia, Italy. E-mail: gerlir@unipg.it

Accepted for publication August 22, 2007.

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