Expression of the markers BDCA-2 and BDCA-4 and production of interferon-alpha by plasmacytoid dendritic cells in systemic lupus erythematosus
2003 (English)In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 48, no 9, 2524-2532 p.Article in journal (Refereed) Published
To study the expression of blood dendritic cell antigen 2 (BDCA-2) and BDCA-4 molecules by plasmacytoid dendritic cells (PDCs) in the blood of patients with systemic lupus erythematosus (SLE), and to study PDC production of interferon-α (IFNα) and its inhibition by anti–BDCA-2 and anti–BDCA-4 antibodies.
Peripheral blood mononuclear cells (PBMCs) from SLE patients (SLE PBMCs) and from healthy controls were induced to produce IFNα in vitro by SLE serum containing an endogenous IFNα-inducing factor (SLE-IIF) or by herpes simplex virus type 1 (HSV-1). The frequencies and numbers of BDCA-2–, BDCA-3–, and BDCA-4–expressing cells were analyzed by flow cytometry, and the effects of anti–BDCA-2 and anti–BDCA-4 monoclonal antibodies (mAb) on IFNα production were investigated.
IFNα production by SLE PBMCs induced by SLE-IIF or HSV-1 was decreased compared with that of healthy control PBMCs (P = 0.002 and P = 0.0007, respectively). The proportions of BDCA-2– and BDCA-3–expressing cells in SLE PBMCs were reduced compared with those in PBMCs from healthy controls (P = 0.01 and P = 0.004, respectively). IFNα producers in culture, especially among SLE PBMCs, displayed reduced BDCA-2 expression and constituted only a minority of the BDCA-2–positive cells, at least in healthy control PBMCs (median 18%). IFNα production by both SLE and healthy control PBMCs stimulated by SLE-IIF or HSV-1 was markedly reduced by anti–BDCA-2 mAb (median 81–98% inhibition). Anti–BDCA-4 mAb only partially inhibited SLE-IIF–induced IFNα production.
SLE patients had a reduced number of BDCA-2–expressing PDCs, also termed natural IFNα-producing cells, and their IFNα production could be inhibited by anti–BDCA-2/4 mAb. Such mAb may be a therapeutic option for inhibiting the ongoing IFNα production in SLE patients.
Place, publisher, year, edition, pages
John Wiley & Sons, 2003. Vol. 48, no 9, 2524-2532 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-87945DOI: 10.1002/art.11225ISI: 000185431900017PubMedID: 13130472OAI: oai:DiVA.org:liu-87945DiVA: diva2:601200