Patients with Systemic Lupus Erythematosus have Reduced Numbers of Circulating Natural Interferon-α- Producing Cells

Cederblad, Britta; Blomberg, Stina; Vallin, Helena; Perers, Anders; Alm, Gunnar V.; Rönnblom, Lars

doi:10.1006/jaut.1998.0215

Cited by 203 publications

(157 citation statements)

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“…*Statistically significant differences were considered when P \ 0.05 (Mann-Whitney U test) (Table 1). Indeed, our results were in agreement with previous reports demonstrating a lower number of peripheral DCs in SLE patients when compared with healthy subjects [32][33][34] but disagreed with others reporting significant alterations in the proportion of circulating mDCs/ pDC subtypes [35]. Those apparent discrepancies in the relative distribution of different peripheral DC subpopulations are probably due to the fact that in other works, they did not include a DC subpopulation, defined by us as CD14 -/low CD16 ?…”

Section: Discussionsupporting

confidence: 77%

Functional characterization of peripheral blood dendritic cells and monocytes in systemic lupus erythematosus

Henriques¹,

Inês

Carvalheiro³

et al. 2011

Rheumatol Int

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With the purpose of contributing to a better knowledge of the APCs functional activity in SLE, we evaluated the distribution and functional ability to produce pro-inflammatory cytokines (TNF-a, IL-1b, IL-6 and IL-12) of peripheral blood (PB) monocytes and DC (tDC), particularly myeloid (mDC) and CD14 -/low CD16 ? DC subpopulations comparing them with those obtained from healthy individuals. The study was performed in 34 SLE patients with diverse disease activity scores (SLEDAI) and 13 healthy age-and sex-matched controls (NC). Our results show an overall decrease in absolute number and relative frequency of tDC in SLE patients with active disease when compared to those with inactive disease and NC, although this decrease did not seem to have an effect on the distribution of PB DC subsets. The monocytes number in SLE patients was similar to those found in NC, whereas a higher frequency of monocytes producing cytokines as well as the amount of each cytokine per cell found without stimulation was particularly observed in those patients with active disease. After stimulation, we observed a higher frequency of IL-12-producing monocytes in active SLE patients. On the other hand, we found among DCs higher frequencies of cytokine-producing CD14 -/low CD16 ? DCs and a higher amount of cytokines produced per cell, particularly in active disease. These findings support an increased production of inflammatory cytokines by APCs in active SLE, mostly associated with alterations in CD14 -/low CD16 ? DC subset homeostasis that might contribute to explain the dynamic role of these cells in disease pathogenesis.

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Section: Discussionsupporting

confidence: 77%

Functional characterization of peripheral blood dendritic cells and monocytes in systemic lupus erythematosus

Henriques¹,

Inês

Carvalheiro³

et al. 2011

Rheumatol Int

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“…NIPCs/PDCs. The number of circulating NIPCs/ PDCs in patients with SLE is reduced Ͼ70-fold compared with that in normal individuals (40); this observation has been confirmed in several studies (41)(42)(43). The remaining cells have an intact IFN␣-producing capacity and express the cell surface antigens BDCA-2 and BDCA-4 (42).…”

Section: Introductionsupporting

confidence: 55%

The type I interferon system in systemic lupus erythematosus

Rönnblom

Eloranta

Alm

2006

Arthritis & Rheumatism

304

246

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“…The concentration of IFN␣ in culture supernatants was measured by DELFIA, as previously described (37). Briefly, microtiter plates coated with the anti-IFN␣ monoclonal antibody LT27:293, which recognizes most IFN␣ subtypes, but not IFN␣2, were incubated for 1 hour at 37°C with the europium-labeled LT27:297 anti-IFN␣ monoclonal antibody and either samples or IFN␣ standard, calibrated against the National Institutes of Health reference leukocyte IFN␣ GA-23-02-530.…”

Section: Methodsmentioning

confidence: 99%

“…The NIPC/PDCs are reduced in number in the blood of SLE patients (37,38), but can be demonstrated in increased number in the skin (39,40), probably reflecting a more general recruitment of these cells to tissues in SLE. Such findings further indicate that NIPC/PDCs and IFN␣ are involved in the pathogenic process of SLE.…”

mentioning

confidence: 98%

Induction of interferon‐α production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG

Lövgren

Eloranta

Båve

et al. 2004

Arthritis & Rheumatism

507

411

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Objective. To investigate the release of interferon-␣ (IFN␣)-inducing material by necrotic or apoptotic cells, its properties, and the necessity of autoantibodies from systemic lupus erythematosus (SLE) patients for the interferogenic activity.Methods. U937 monocytic leukemia cells or peripheral blood mononuclear cells (PBMCs) were rendered necrotic by freeze-thawing or apoptotic by treatment with ultraviolet light. Cell culture supernatants from these cells and IgG from SLE patients (SLE IgG) were added to cultures of normal PBMCs or purified plasmacytoid dendritic cells (PDCs). The importance of nucleic acids for IFN␣ induction was investigated by RNase and DNase treatment. The IFN␣ levels were measured by immunoassay.Results. Both necrotic and apoptotic U937 cells released material that, combined with SLE IgG, induced IFN␣ production in PDCs. The release from apoptotic cells occurred with a 16-hour delay, in late apoptosis. Also, normal PBMCs released IFN␣-inducing material, but only during necrosis. The interferogenic activity of the necrotic material required the presence of RNA, while both RNA and DNA were important in the apoptotic material. In both cases, the presence of SLE IgG was necessary, and its activity correlated with the presence of antibodies to RNA-binding proteins, but not anti-DNA antibodies.Conclusion. Necrotic and late apoptotic cells release material that, combined with SLE IgG, induces production of IFN␣ in PDCs. The IFN␣ inducers probably consist of immune complexes (ICs) containing RNA and possibly DNA as essential interferogenic components. The presence of such interferogenic ICs could explain the ongoing production of IFN␣ in SLE and could be of etiopathogenic importance.

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Patients with Systemic Lupus Erythematosus have Reduced Numbers of Circulating Natural Interferon-α- Producing Cells

Cited by 203 publications

References 0 publications

Functional characterization of peripheral blood dendritic cells and monocytes in systemic lupus erythematosus

Functional characterization of peripheral blood dendritic cells and monocytes in systemic lupus erythematosus

The type I interferon system in systemic lupus erythematosus

Induction of interferon‐α production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG

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