Alterations of dendritic cells in systemic lupus erythematosus: Phenotypic and functional deficiencies

Abstract

Objective. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by B cell hyperactivity and defective T cell functions, including interleukin-2 production and proliferation. The defects in T cell function may result from underlying defects in antigen-presenting cell (APC) function. The present study was undertaken to investigate phenotypic and functional characteristics of peripheral blood dendritic cells (DC), as the most potent APC, in SLE patients in comparison with healthy controls.Methods. Samples from 25 SLE patients and 15 healthy controls were studied. To identify DC, peripheral blood mononuclear cells were double stained with monoclonal antibodies against lineage marker (lin)-specific molecules CD3, CD19, CD14, and CD16, versus CD4. DC were characterized phenotypically by flow cytometry. The stimulatory capacity of DC was determined by proliferation of T cells in the mixed lymphocyte reaction (MLR), which was assessed by measurement of tritiated thymidine incorporation in studies using granulocyte-macrophage colonystimulating factor-activated, DC-enriched APC. Correlations between DC counts and phenotype and clinical parameters in SLE patients were determined.Results. Lin؊,HLA-DR؉,CD4؉ DC were, on average, 50% less frequent in SLE patients than in controls. Moreover, among DC, the proportions of B7؉ and CD40؉ cells were reduced and, in particular, the

Clinical significance of circulating dendritic cells in patients with systemic lupus erythematosus

“…These observations are partially consistent with previous reports. 21,28 Scheinecker et al showed that the DC count in patients with SLE was 50) lower than in the control, regarding the number of CD11 ' cells (mDC) even 80) lower. 20 However, unlike those results, our study showed a number of CD11 ' mDC in SLE patients similar to the healthy control.…”

“…Our data showed negative, but not statistically significant, correlation of the number of tDC and their subsets with activity of SLE assessed by the Systemic Lupus Activity Measure scale. Similar results, although in distinctly smaller groups of SLE patients, were described by Scheinecker et al 21 They showed that the tDC population inversely correlated with the activity of the disease, defined according to the European Consensus Lupus Activity Measurement scale (r0/(/0.56, p 0/0.01). However, unlike our study, they did not correlate the SLE activity with particular DC subpopulations.…”

“…Positive correlation between total numbers of lymphocytes and DCs has been also observed by other authors. 21 It should be stressed that in other lymphopenia-associated disorders (AIDS), as well as in advanced neoplastic diseases, a decrease in peripheral blood DC count was also described. 32,33 There was no statistically significant relationship to other laboratory or clinical features of SLE, such as antinuclear antibodies level, anemia, thrombocytopenia, as well as the presence of skin, renal or neurological symptoms, which could be due to a small number of patients with particular SLE symptoms.…”

“…20 In pediatric SLE patients undergoing steroid therapy, DC numbers were over 70) lower than in the control group. 21 22 In the present study we assessed the total number of circulating DCs and their plasmacytoid and myeloid subpopulations defined by a novel panel of mAbs directed against BDCA antigens. We also correlated the number of DCs with peripheral blood immunocompetent cells that are involved in SLE pathogenesis.…”

Immunothérapies du lupus systémique : innovations et perspectives

“…Un des éléments majeurs dans la pathogénie du LES a été la mise en évidence du rôle majeur des cellules dendritiques (CD) [99,100]. Au cours du LES, il a été observé que les monocytes circulants, contrairement à des sujets témoins, pouvaient se différencier en CD sous l'effet d'une production excessive d'IFN-a [101][102][103][104].…”