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Physiopathology of necrobiotic xanthogranuloma with monoclonal gammopathy.

Szalat R, Pirault J, Fermand JP, Carrié A, Saint-Charles F, Olivier M, Robillard P, Frisdal E, Villard EF, Cathébras P, Bruckert E, Chapman MJ, Giral P, Guerin M, Lesnik P, Le Goff W - J. Intern. Med. (2014)

Bottom Line: This accumulation was due in part to a significant reduction in the HDL capacity to promote cholesterol efflux from macrophages, which was not found in the case of NX.However, patients with NXG were distinguished by elevated levels of IL-15 and a marked increase in the rate of intermediate CD14++CD16+ monocytes.This study revealed that NXG is characterized by impaired macrophage lipid homeostasis associated with a systemic inflammatory profile that may result from the interaction of MIg and lipoproteins.

View Article: PubMed Central - PubMed

Affiliation: Département d'immunologie Clinique, Hôpital Saint Louis, Paris, France; EA3963, Université Paris 7 Denis Diderot, INSERM, IFR105, Institut Universitaire d'Hématologie, Paris, France.

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Phenotyping blood leucocytes in patients with NXG and NX. Absolute counting of (a) CD45-positive leucocytes, (b) T lymphocyte subsets (T helper, Th: CD3+ CD4+; naive Th: CD3+ CD4+ CD25+ CD127+; T regulatory cells, Treg: CD3+ CD4+ CD25hi CD127−; cytotoxic T lymphocytes, CTL: CD3+ CD8+; B lymphocytes, LB: CD3− CD19+; NKT: CD3+ CD16+ and natural killer cells, NK: CD3− CD56+), (c) total monocytes, (d) classical monocytes CD14++CD16−, (e) intermediate monocytes CD14++CD16+, (f) nonclassical monocytes CD14+/CD16++, (g) ratio of intermediate monocytes CD14++CD16+/classical monocytes CD14++CD16− and (h) dendritic cell subsets (plasmacytoid DC, pDC: CD11c− CD123+ BDCA2+; myeloid DC1, mDC1: CD11c+ BDCA1+ BDCA3−; and myeloid DC2, mDC2: CD11c+ BDCA1− BDCA3+) by flow cytometry (LSR II Fortessa Sorp, BD Biosciences) in control (no MIg or xanthoma) (n = 7, green), NXG (n = 6, orange) and NX (n = 6, violet) subjects. *P < 0.05 and **P < 0.005 versus control individuals.
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fig03: Phenotyping blood leucocytes in patients with NXG and NX. Absolute counting of (a) CD45-positive leucocytes, (b) T lymphocyte subsets (T helper, Th: CD3+ CD4+; naive Th: CD3+ CD4+ CD25+ CD127+; T regulatory cells, Treg: CD3+ CD4+ CD25hi CD127−; cytotoxic T lymphocytes, CTL: CD3+ CD8+; B lymphocytes, LB: CD3− CD19+; NKT: CD3+ CD16+ and natural killer cells, NK: CD3− CD56+), (c) total monocytes, (d) classical monocytes CD14++CD16−, (e) intermediate monocytes CD14++CD16+, (f) nonclassical monocytes CD14+/CD16++, (g) ratio of intermediate monocytes CD14++CD16+/classical monocytes CD14++CD16− and (h) dendritic cell subsets (plasmacytoid DC, pDC: CD11c− CD123+ BDCA2+; myeloid DC1, mDC1: CD11c+ BDCA1+ BDCA3−; and myeloid DC2, mDC2: CD11c+ BDCA1− BDCA3+) by flow cytometry (LSR II Fortessa Sorp, BD Biosciences) in control (no MIg or xanthoma) (n = 7, green), NXG (n = 6, orange) and NX (n = 6, violet) subjects. *P < 0.05 and **P < 0.005 versus control individuals.

Mentions: Circulating CD45-positive mononuclear leucocytes were analysed by flow cytometry (Fig.3). The number of total circulating mononuclear leucocytes was not different in patients with NX relative to controls, whereas it was reduced by 57% (P < 0.05) in patients with NXG (Fig.3a). Neutrophil counts were similar in all groups (Figure S2). Absolute counts of T helper lymphocytes (Th), naive T helpers (naive Th), regulatory T cells (Treg), cytotoxic T lymphocytes (CTL) and natural killer cells (NK) were reduced in patients with NXG [by −53%, −61% (P < 0.005), −42%, 77% and −61% (P < 0.05), respectively], whereas the number of lymphocytes (LB) and natural killer T cells (NKT) was not altered (Fig.3b) relative to control individuals. The absolute count of monocytes was nearly the same for all patients (Fig.3c), but the absolute count of classical CD14++/CD16− monocytes was markedly reduced for NXG (by −67%, P < 0.005) but not NX (Fig.3d). The number of intermediate CD14++/CD16+ monocytes was not significantly different for NXG and NX (Fig.3e), whereas the number of nonclassical CD14+/CD16++ monocytes was reduced (by −44%, P = 0.07 for NXG and −57%, P < 0.05 for NX) (Fig.3f). More strikingly, the intermediate/classical monocyte ratio was 76-fold higher for NXG than for the controls, whilst no effect was observed for NX (Fig.3g). Finally, analysis of dendritic cells subsets revealed a reduction in the Th2-promoting mDC2 subpopulation in both NX and NXG (−59% and −51%, P < 0.05, respectively), whilst absolute counts of the pDC and Th1-promoting mDC1 subsets were not significantly different from control subjects (Fig.3h).


Physiopathology of necrobiotic xanthogranuloma with monoclonal gammopathy.

Szalat R, Pirault J, Fermand JP, Carrié A, Saint-Charles F, Olivier M, Robillard P, Frisdal E, Villard EF, Cathébras P, Bruckert E, Chapman MJ, Giral P, Guerin M, Lesnik P, Le Goff W - J. Intern. Med. (2014)

Phenotyping blood leucocytes in patients with NXG and NX. Absolute counting of (a) CD45-positive leucocytes, (b) T lymphocyte subsets (T helper, Th: CD3+ CD4+; naive Th: CD3+ CD4+ CD25+ CD127+; T regulatory cells, Treg: CD3+ CD4+ CD25hi CD127−; cytotoxic T lymphocytes, CTL: CD3+ CD8+; B lymphocytes, LB: CD3− CD19+; NKT: CD3+ CD16+ and natural killer cells, NK: CD3− CD56+), (c) total monocytes, (d) classical monocytes CD14++CD16−, (e) intermediate monocytes CD14++CD16+, (f) nonclassical monocytes CD14+/CD16++, (g) ratio of intermediate monocytes CD14++CD16+/classical monocytes CD14++CD16− and (h) dendritic cell subsets (plasmacytoid DC, pDC: CD11c− CD123+ BDCA2+; myeloid DC1, mDC1: CD11c+ BDCA1+ BDCA3−; and myeloid DC2, mDC2: CD11c+ BDCA1− BDCA3+) by flow cytometry (LSR II Fortessa Sorp, BD Biosciences) in control (no MIg or xanthoma) (n = 7, green), NXG (n = 6, orange) and NX (n = 6, violet) subjects. *P < 0.05 and **P < 0.005 versus control individuals.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4279948&req=5

fig03: Phenotyping blood leucocytes in patients with NXG and NX. Absolute counting of (a) CD45-positive leucocytes, (b) T lymphocyte subsets (T helper, Th: CD3+ CD4+; naive Th: CD3+ CD4+ CD25+ CD127+; T regulatory cells, Treg: CD3+ CD4+ CD25hi CD127−; cytotoxic T lymphocytes, CTL: CD3+ CD8+; B lymphocytes, LB: CD3− CD19+; NKT: CD3+ CD16+ and natural killer cells, NK: CD3− CD56+), (c) total monocytes, (d) classical monocytes CD14++CD16−, (e) intermediate monocytes CD14++CD16+, (f) nonclassical monocytes CD14+/CD16++, (g) ratio of intermediate monocytes CD14++CD16+/classical monocytes CD14++CD16− and (h) dendritic cell subsets (plasmacytoid DC, pDC: CD11c− CD123+ BDCA2+; myeloid DC1, mDC1: CD11c+ BDCA1+ BDCA3−; and myeloid DC2, mDC2: CD11c+ BDCA1− BDCA3+) by flow cytometry (LSR II Fortessa Sorp, BD Biosciences) in control (no MIg or xanthoma) (n = 7, green), NXG (n = 6, orange) and NX (n = 6, violet) subjects. *P < 0.05 and **P < 0.005 versus control individuals.
Mentions: Circulating CD45-positive mononuclear leucocytes were analysed by flow cytometry (Fig.3). The number of total circulating mononuclear leucocytes was not different in patients with NX relative to controls, whereas it was reduced by 57% (P < 0.05) in patients with NXG (Fig.3a). Neutrophil counts were similar in all groups (Figure S2). Absolute counts of T helper lymphocytes (Th), naive T helpers (naive Th), regulatory T cells (Treg), cytotoxic T lymphocytes (CTL) and natural killer cells (NK) were reduced in patients with NXG [by −53%, −61% (P < 0.005), −42%, 77% and −61% (P < 0.05), respectively], whereas the number of lymphocytes (LB) and natural killer T cells (NKT) was not altered (Fig.3b) relative to control individuals. The absolute count of monocytes was nearly the same for all patients (Fig.3c), but the absolute count of classical CD14++/CD16− monocytes was markedly reduced for NXG (by −67%, P < 0.005) but not NX (Fig.3d). The number of intermediate CD14++/CD16+ monocytes was not significantly different for NXG and NX (Fig.3e), whereas the number of nonclassical CD14+/CD16++ monocytes was reduced (by −44%, P = 0.07 for NXG and −57%, P < 0.05 for NX) (Fig.3f). More strikingly, the intermediate/classical monocyte ratio was 76-fold higher for NXG than for the controls, whilst no effect was observed for NX (Fig.3g). Finally, analysis of dendritic cells subsets revealed a reduction in the Th2-promoting mDC2 subpopulation in both NX and NXG (−59% and −51%, P < 0.05, respectively), whilst absolute counts of the pDC and Th1-promoting mDC1 subsets were not significantly different from control subjects (Fig.3h).

Bottom Line: This accumulation was due in part to a significant reduction in the HDL capacity to promote cholesterol efflux from macrophages, which was not found in the case of NX.However, patients with NXG were distinguished by elevated levels of IL-15 and a marked increase in the rate of intermediate CD14++CD16+ monocytes.This study revealed that NXG is characterized by impaired macrophage lipid homeostasis associated with a systemic inflammatory profile that may result from the interaction of MIg and lipoproteins.

View Article: PubMed Central - PubMed

Affiliation: Département d'immunologie Clinique, Hôpital Saint Louis, Paris, France; EA3963, Université Paris 7 Denis Diderot, INSERM, IFR105, Institut Universitaire d'Hématologie, Paris, France.

Show MeSH
Related in: MedlinePlus