Anti-tumor necrosis factor-alpha response in rheumatoid arthritis is associated with an increase in serum soluble CD30.
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.


CONCLUSIONS
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-alpha. 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.
Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy. gerlir@unipg.it
Roberto
R
Gerli
Claudio
C
Lunardi
Elena Bartoloni
EB
Bocci
Francesca
F
Bobbio-Pallavicini
Giuseppe
G
Schillaci
Roberto
R
Caporali
Onelia
O
Bistoni
Matteo
M
Pirro
Costantino
C
Pitzalis
Carlomaurizio
C
Montecucco
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D015415:Biomarkers; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D000069285:Infliximab; D017730:Ki-1 Antigen / Q000097:blood / Q000187:drug effects*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017211:Treatment Failure; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D017730:Ki-1 Antigen; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab