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

Scheinecker, Clemens; Zwölfer, Bettina; Köller, Marcus; Manner, Georg; Smolen, Josef S.

doi:10.1002/1529-0131(200104)44:4<856::aid-anr142>3.0.co;2-a

Cited by 91 publications

(44 citation statements)

References 43 publications

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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: 76%

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: 76%

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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“…It was suggested that patients with SLE have increased differentiation of precursor cells into monocyte-derived DC due to the effect of IFN-a produced by pDC [13]. Myeloid DC were found to be either spontaneously hypo- [14,15] or hyperactivated [16,17] with a decreased [14,15] or increased [17] mixed lymphocyte reaction (MLR). However, their capacity and function following apoptotic cell interaction was not examined.…”

Section: Introductionmentioning

confidence: 69%

Altered dendritic cells with tolerizing phenotype in patients with systemic lupus erythematosus

et al. 2008

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Earlier we showed the generation of tolerizing human monocyte-derived DC following interaction with iC3b-opsonized apoptotic cells. In this study we examine the generation of DC with our previously described tolerogenic phenotype in patients with the systemic autoimmune disease systemic lupus erythematosus (SLE). Monocyte-derived DC were generated in 71 SLE patients, characterized, and then tested for clearance of iC3b-opsonized 1,1 0 -dioctadecyl-3,3,3 0 ,3 0 -tetramethyl-indocarbocyanineperchlorate-stained apoptotic cells using flow cytometry, and for autologous T-cell activation using autologous mixed lymphocyte reaction (AMLR), at the same time as controls. Compared with healthy, ageand gender-matched controls, SLE patients showed upregulation of MHC class II, with a mean expression of 130.5%736.8% (po0.007); CD86 in immature DC from SLE patients, generated in autologous human or control plasma, were also upregulated, with mean expression 106.6%718.0% (po0.03). A significant (420%) reduction in iC3b-apoptotic cell uptake, together with increased autologous mixed lymphocyte reaction, was seen in 75% of SLE patients. Mean 1,1 0 -dioctadecyl-3,3,3 0 ,3 0 -tetramethyl-indocarbocyanineperchloratestained apoptotic cell acquisition was 70.0%724% (po0.0001) compared with healthy controls. Altered generation of a tolerizing DC phenotype was seen in at least one third of SLE patients following interaction with iC3b-opsonized apoptotic cells. These results suggest that a substantial portion of SLE patients fail to generate DC with a tolerizing phenotype.

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“…The effects of previous influenza vaccinations or natural infections could not be completely excluded. Whether intrinsic defects are involved, such as a defective antigen-presenting cell function (32,33), is uncertain.…”

Section: Discussionmentioning

confidence: 99%

Studies of cell‐mediated immune responses to influenza vaccination in systemic lupus erythematosus

Holvast¹,

Assen²,

Haan³

et al. 2009

Arthritis & Rheumatism

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Objective. Both antibody and cell-mediated responses are involved in the defense against influenza. In patients with systemic lupus erythematosus (SLE), a decreased antibody response to subunit influenza vaccine has been demonstrated, but cell-mediated responses have not yet been assessed. This study was therefore undertaken to assess cell-mediated responses to influenza vaccination in patients with SLE.Methods. Fifty-four patients with SLE and 54 healthy control subjects received subunit influenza vaccine. Peripheral blood mononuclear cells and sera were obtained before and 1 month after vaccination. Cellmediated responses to A/H1N1 and A/H3N2 vaccines were evaluated using an interferon-␥ (IFN␥) enzymelinked immunospot assay and flow cytometry. Antibody responses were measured using a hemagglutination inhibition test.Results. Prior to vaccination, patients with SLE had fewer IFN␥ spot-forming cells against A/H1N1 compared with control subjects and a lower frequency of IFN␥-positive CD8؉ T cells. After vaccination, the number of IFN␥ spot-forming cells increased in both patients and control subjects, although the number remained lower in patients. In addition, the frequencies of CD4؉ T cells producing tumor necrosis factor and interleukin-2 were lower in patients after vaccination compared with healthy control subjects. As expected for a subunit vaccine, vaccination did not induce a CD8؉ T cell response. For A/H3N2-specific responses, results were comparable. Diminished cell-mediated responses to influenza vaccination were associated with the use of prednisone and/or azathioprine. The increase in A/H1N1-specific and A/H3N2-specific antibody titers after vaccination was lower in patients compared with control subjects.Conclusion. In addition to a decreased antibody response, cell-mediated responses to influenza vaccination are diminished in patients with SLE, which may reflect the effects of the concomitant use of immunosuppressive drugs. This may render these patients more susceptible to (complicated) influenza infections.

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

Cited by 91 publications

References 43 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

Altered dendritic cells with tolerizing phenotype in patients with systemic lupus erythematosus

Studies of cell‐mediated immune responses to influenza vaccination in systemic lupus erythematosus

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