Immunosuppressive Activity of Abatacept on Circulating T Helper Lymphocytes from Juvenile Idiopathic Arthritis Patients.
BACKGROUND
Abatacept is used in the treatment of juvenile idiopathic arthritis (JIA) patients, but the activity of the drug on T helper cell function is not yet fully known.


METHODS
The ability of abatacept to affect cytokine production in vitro and the proliferative response to both recall antigens and polyclonal stimulation was firstly assessed in healthy donors. Then, 10 JIA patients who were due to start abatacept treatment were recruited and longitudinally evaluated during the first 90 days of therapy. Both their clinical response to the treatment and in vitro analysis aimed to assess the proliferative response to recall antigens and the proportions of circulating T helper subsets.


RESULTS
Abatacept reduced the proliferative response to recall antigens and the production of proinflammatory cytokines such as IFN-γ and TNF-α in healthy donors in vitro. It was also efficient in improving symptoms and reducing parameters of inflammation in JIA patients. Abatacept reduced the proliferative response to recall antigens, and this effect was significant soon after drug infusion (2 days). Regarding the proportions of circulating CD4+ T lymphocytes, only a reduction in the frequencies of circulating Treg cells was observed.


CONCLUSIONS
Abatacept in vitro inhibits proliferation and cytokine production in healthy donors, and reduces parameters of inflammation in vivo in JIA patients. The reduction of the proliferative response to recall antigens induced by abatacept was evident only soon after drug administration, suggesting that its immunosuppressive activity is maintained only for a short time.
Department of Experimental and Clinical Medicine and DENOTHE Center, University of Florence, Florence, Italy.
Laura
L
Maggi
Rolando
R
Cimaz
Manuela
M
Capone
Veronica
V
Santarlasci
Maria Caterina
MC
Rossi
Alessio
A
Mazzoni
Gianni
G
Montaini
Ilaria
I
Pagnini
Teresa
T
Giani
Gabriele
G
Simonini
Cristina
C
Scaletti
Francesco
F
Liotta
Enrico
E
Maggi
Francesco
F
Annunziato
Lorenzo
L
Cosmi
D000069594:Abatacept / Q000494:pharmacology* / Q000627:therapeutic use; D000293:Adolescent; D000941:Antigens / Q000276:immunology; D001171:Arthritis, Juvenile / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D002648:Child; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018836:Inflammation Mediators; D008213:Lymphocyte Activation; D008297:Male; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism
D000941:Antigens; D016207:Cytokines; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D000069594:Abatacept