Reduced levels of circulating progenitor cells in juvenile idiopathic arthritis are counteracted by anti TNF-α therapy.
BACKGROUND
Endothelial progenitor cells (EPC) promote angiogenesis and vascular repair. Though reduced EPC levels have been shown in rheumatoid arthritis, no study has so far evaluated EPCs in children with juvenile idiopathic arthritis (JIA). We aimed to study circulating EPCs in children with JIA, their relation to disease activity, and effects of anti TNF-α treatment.


METHODS
Circulating EPCs were quantified by flow cytometry based on CD34, CD133 and KDR expression in peripheral blood of 22 patients with oligoarticular JIA and 29 age-matched controls. EPCs were re-assessed in children with methotrexate-resistant oligo-extended JIA before and up to 12 month after initiation of anti-TNF-alpha therapy. Plasma concentrations of inflammatory and EPC-regulating factors were measured using a multiplex array. Confocal immunofluorescence was used to demonstrate EPCs in synovial tissues.


RESULTS
Children with active JIA showed a significant reduction of relative and absolute counts of circulating progenitor cells and EPCs compared to age-matched healthy controls. CD34(+) cell levels were modestly and inversely correlated to disease activity. A strong inverse correlation was found between serum TNF-α and EPC levels. In 8 patients treated with anti TNF-α agents, the number of EPCs rose to values similar to healthy controls. CD34(+)KDR(+) EPCs were found in the synovial tissue of JIA children, but not in control.


CONCLUSIONS
Children with JIA have reduced levels of the vasculoprotective and proangiogenic EPCs. While EPCs may contribute to synovial tissue remodelling, EPC pauperization may indicate an excess cardiovascular risk if projected later in life.
Paediatric Rheumatology Unit, Department of Paediatrics, 35128, Padova, Italy. martini@pediatria.unipd.it.
Giorgia
G
Martini
Paediatric Rheumatology Unit, Department of Paediatrics, 35128, Padova, Italy. francesca.biscaro@ulssasolo.ven.it.
Francesca
F
Biscaro
Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy. elisaboscaro@ymail.com.
Elisa
E
Boscaro
Department of Cardiovascular and Thoracic Sciences, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy. fiorella.calabrese@unipd.it.
Fiorella
F
Calabrese
Department of Cardiovascular and Thoracic Sciences, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy. francescalunardi@libero.it.
Francesca
F
Lunardi
Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy. monica.facco@unipd.it.
Monica
M
Facco
Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy. carlo.agostini@unipd.it.
Carlo
C
Agostini
Paediatric Rheumatology Unit, Department of Paediatrics, 35128, Padova, Italy. zulian@pediatria.unipd.it.
Francesco
F
Zulian
Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy. gianpaolo.fadini@unipd.it.
Gian Paolo
GP
Fadini
D000071916:AC133 Antigen; D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood; D001171:Arthritis, Juvenile / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D010455:Peptides / Q000097:blood; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood; D055815:Young Adult
D000071916:AC133 Antigen; D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D040301:Vascular Endothelial Growth Factor Receptor-2