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Different immunological alterations may condition systemic lupus erythematosus (SLE) activity. However, it is not known whether alterations in the phenotype of circulating antigen-presenting cells (APCs) and in the response to CpG oligodeoxynucleotides (ODN-CpG) correlate with disease activity. APC expression of HLA-DR, costimulatory molecules, and TLR9 expression was determined in patients with SLE, other autoimmune diseases, and healthy controls.Monocyte and B cell response to synthetic ODN-CpG sequences was also evaluated. Monocytes from patients with moderate SLE activity had higher expression of CD40 and CD86. Decreased numbers of CD19+ CD80+ and BDCA-3+CD40+ cells were found in patients with severe SLE activity. In patients with moderate SLE activity, non-adherent and enriched B cell response to ODN-CpG was similar to healthy controls. Adherent and enriched B cells from patients with severe SLE activity did not increase costimulatory molecule expression or cytokine production after ODN-CpG stimulation. APCs frompatients with SLE, regardless of disease activity, displayed higher percentage of TLR9+ cells, as well as increased expression of TLR9, compared to healthy controls. Results suggest that the B cell response to ODN-CpG correlates with the SLE activity, independently of TLR9 expression, indicating that alterations in B cell response in severe activity SLE may be caused by events down-stream to TLR9. [ABSTRACT FROM AUTHOR]

Dendntic cells (DCs) are functionally abnormal in systemic lupus erythematosus (SLE). However, previous studies have involved in-vitro cytokine-induced DCs. In this investigation, directly isolated circulating plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) in SLE were studied. Blood dendritic cell antigen (BDCA)-4 and BDCA-1 magnetic isolation kits were used to isolate blood pDCs and mDCs from 30 SLE patients and 36 controls. Their number and surface markers, and their relationship with lupus disease activity were evaluated. The percentage of pDCs per peripheral blood mononuclear cells was higher in SLE (0.33 ± 0.14) than in controls (0.16 ± 0.09, P <0.01), but that of mDCs was lower in SLE (0.43 ± 0.14) than in controls (0.63 ± 0.32; P < 0.01). In controls, both pDCs and mDCs expressed high levels of MHC-II, however, the expression of CD86, CD83 and CCR7 on pDCs were significantly lower than that on mDCs (all P < 0.05). mDCs from patients with SLE, particularly those with active disease, expressed lower CD83 than controls. In health, circulating mDCs may be more efficient than pDCs in stimulating T cells. In SLE, the increased number of circulating pDCs supports a pathogenic role for these cells, and the decreased mDC number and CD83 expression may explain the susceptibility to infections in these patients. [ABSTRACT FROM AUTHOR]

Genetic determinants taking part in the development of systemic lupus erythematosus (SLE) are complex and not fully characterized. Dysregulated expression of genes involved in the control of apoptosis has been previously suggested. We report here a consanguineous family with SLE manifestations in three siblings associated in one of them with severe lymphoproliferative features. Laboratory studies showed no defect in CD95-mediated cell death. Screening expression of Bcl-2 family genes that regulate mitochondrial apoptosis pathway showed an overexpression of the antiapoptotic Bfl-1 gene. Real time RT-PCR analysis indicated that overexpression of Bfl-1 was restricted to B-cells, with normal expression in T-cells. Those results suggest that overexpression of Bfl-1 could result in impaired B-lymphocyte homeostasis and inappropriate immune response leading to autoimmune manifestations. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can be exacerbated by exposure to ultraviolet radiation (UVR). The number and phenotype of antigen presenting cells in the skin play a role in cutaneous immune response generation. Although antimalarials are widely used in SLE treatment, their mode of action is not completely elucidated. The aim of our study was to determine the effect of chloroquine treatment on HLA-DR+ and CD1a+ cell number in locally irradiated (three minimal erythema doses of UVB) and normal appearing skin in SLE patients and healthy subjects. A significantly higher number of HLA-DR+ and CD1a+ cells were found in both locations in SLE patients compared with controls. Following three months of daily chloroquine treatment (250 mg), the HLA-DR+ and CD1a+ cell counts were significantly reduced in both irradiated and unirradiated sites of SLE patients, although still higher than in controls. Chloroquine treatment reduces the number of antigen presenting cells in the skin of SLE patients, and this effect may explain the antimalarials beneficial immunoregulatory and anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

CD80 and CD86, expressed on the antigen-presenting cells (APCs) provide costimulatory signals for T lymphocytes. Recently, defective expression of CD80 has been reported in systemic lupus erythematosus (SLE) although its mechanism is unclear. Here, expression of the B7 antigens induced by interferon-γ, interleukin-4 or granulocyte-macrophage stimulating-factor (GM-CSF) along the differentiation process of APCs was investigated. In contrast to CD86, expression of CD80 on the CD14[sup +] cells induced by GM-CSF was reduced in SLE. GM-CSF receptor (GMCSFR) was down-regulated by GM-CSF or phorbol 12-myristate 13-acetate in both of the normal controls and SLE patients, while this change was more remarkable in the latter. In the presence of 1-(5-isoquinolinsulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C, the PMA-induced down-regulation of GM-CSFR was reversed in the normal controls but not in SLE. These data suggest that dysregulation of the GM-CSFR might be associated with the defective expression of CD80, leading to dysfunction of the APCs in SLE. [ABSTRACT FROM AUTHOR]