IFNα serum levels are associated with endothelial progenitor cells imbalance and disease features in rheumatoid arthritis patients.
BACKGROUND
IFNα has been largely implicated in the ethiopathogenesis of autoimmune diseases but only recently it has been linked to endothelial damage and accelerated atherosclerosis in autoimmunity. In addition, proinflammatory conditions are supposed to be implicated in the cardiovascular status of these patients. Since a role for IFNα in endothelial damage and impaired Endothelial Progenitor Cell (EPC) number and function has been reported in other diseases, we aimed to evaluate the potential associations of IFNα serum levels on EPC populations and cytokine profiles in Rheumatoid Arthritis (RA) patients.


METHODS
pre-EPC, EPC and mature EPC (mEPC) populations were quantified by flow cytometry analyzing their differential CD34, CD133 and VEGFR2 expression in blood samples from 120 RA patients, 52 healthy controls (HC), and 83 systemic lupus erythematosus (SLE) patients as disease control. Cytokine serum levels were measured by immunoassays and clinical and immunological data, including cardiovascular (CV) events and CV risk factors, were retrospectively obtained by reviewing clinical records.


RESULTS
Long-standing, but not recent onset RA patients displayed a significant depletion of all endothelial progenitor populations, unless high IFNα levels were present. In fact, the IFN(high) RA patient group (n = 40, 33%), showed increased EPC levels, comparable to SLE patients. In addition, high IFNα serum levels were associated with higher disease activity (DAS28), presence of autoantibodies, higher levels of IL-1β, IL-6, IL-10 and MIP-1α, lower amounts of TGF-β, and increased mEPC/EPC ratio, thus suggesting higher rates of endothelial damage and an endothelial repair failure. Finally, the relationship between high IFNα levels and occurrence of CV events observed in RA patients seems to support this hypothesis.


CONCLUSIONS
IFNα serum marker could be used to identify a group of RA patients with increased disease activity, EPC imbalance, enhanced proinflammatory profile and higher cardiovascular risk, probably due, at least in part, to an impaired endothelial repair.
Area Of Immunology, Department Of Functional Biology, Faculty Of Medicine, University Of Oviedo, Oviedo, Spain.
Javier
J
Rodríguez-Carrio
Area Of Immunology, Department Of Functional Biology, Faculty Of Medicine, University Of Oviedo, Oviedo, Spain.
Banesa
B
de Paz
Area Of Immunology, Department Of Functional Biology, Faculty Of Medicine, University Of Oviedo, Oviedo, Spain.
Patricia
P
López
Area Of Immunology, Department Of Functional Biology, Faculty Of Medicine, University Of Oviedo, Oviedo, Spain.
Catuxa
C
Prado
Department Of Rheumatology, Hospital Universitario Central De Asturias, Oviedo, Spain.
Mercedes
M
Alperi-López
Department Of Rheumatology, Hospital Universitario Central De Asturias, Oviedo, Spain.
Francisco Javier
FJ
Ballina-García
Area Of Immunology, Department Of Functional Biology, Faculty Of Medicine, University Of Oviedo, Oviedo, Spain.
Ana
A
Suárez
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology / Q000473:pathology*; D002318:Cardiovascular Diseases / Q000097:blood / Q000473:pathology; D002465:Cell Movement; D003710:Demography; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016898:Interferon-alpha / Q000097:blood*; D008297:Male; D008875:Middle Aged; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
D016898:Interferon-alpha