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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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Patients with NX and NXG exhibit a unique inflammatory pattern. Circulating levels of cytokines (a–b, e, f and g), soluble receptors (c) and adhesion molecules (d) were quantified in plasma from normolipidaemic control (no MIg or xanthoma) (n = 8, open bars), NXG (n = 8, dark bars), NX (n = 8, light grey bars), MIg controls (no MIg or xanthoma) (dark grey bars) and xanthoma controls (FH patients without MIg and with xanthoma) (n = 7, hatched bars) individuals as determined on a semi-automated biochip array analyzer (Randox). *P < 0.05, **P < 0.005 and ***P <0.0005 versus control plasma. Amounts of ADAM17 (h) or CCR2 (i) mRNA in freshly isolated CD14-positive monocytes from control (n = 9), NX (n = 6) and NXG (n = 4) subjects. *P < 0.05 relative to the control.
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fig04: Patients with NX and NXG exhibit a unique inflammatory pattern. Circulating levels of cytokines (a–b, e, f and g), soluble receptors (c) and adhesion molecules (d) were quantified in plasma from normolipidaemic control (no MIg or xanthoma) (n = 8, open bars), NXG (n = 8, dark bars), NX (n = 8, light grey bars), MIg controls (no MIg or xanthoma) (dark grey bars) and xanthoma controls (FH patients without MIg and with xanthoma) (n = 7, hatched bars) individuals as determined on a semi-automated biochip array analyzer (Randox). *P < 0.05, **P < 0.005 and ***P <0.0005 versus control plasma. Amounts of ADAM17 (h) or CCR2 (i) mRNA in freshly isolated CD14-positive monocytes from control (n = 9), NX (n = 6) and NXG (n = 4) subjects. *P < 0.05 relative to the control.

Mentions: Serum CRP levels were slightly elevated in patients with NXG and NX (7.96 ± 3.48 and 5.77 ± 2.65 mg L−1, respectively) (Table2). Circulating inflammatory cytokines and adhesion molecules were quantified using biochip arrays (Fig.4). Results were compared with data obtained with plasma from both normolipidaemic controls with or without MIg and patients with FH who had xanthoma and high plasma cholesterol levels but no detectable monoclonal gammopathy. In patients with NX and NXG, a marked increase in the plasma levels of pro-inflammatory cytokines (TNFα and IL-6) (Figs4b), soluble cytokine receptors (sIL-6R, sTNFRI and sTNFRII) (Fig.4c) and adhesion molecules (VCAM-1 and ICAM-1) (Fig.4d) was observed relative to all control groups. Levels of the plasma chemokines MCP-1, MIP-1α and IL-8 were also elevated in patients with NX and NXG. A similar increase in MCP-1 and IL-8 levels was also observed in normolipidaemic controls with MIg (Fig.4e). Although patients with NX displayed an overlapping pro-inflammatory pattern with patients with NXG, some differences were detected. For example, the NXG pattern was distinguished by an increase in plasma IL-15 levels (+62%, P < 0.05) (Fig.4f), whilst the NX pattern was characterized by an elevation of both plasma IFNγ and EGF levels (2.4- and 4.4-fold, respectively, P < 0.05) (Figs4a, e). Of note, plasma IFNγ levels were positively correlated with EGF levels in patients with NX and NXG (r = −0.412, P < 0.05).


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)

Patients with NX and NXG exhibit a unique inflammatory pattern. Circulating levels of cytokines (a–b, e, f and g), soluble receptors (c) and adhesion molecules (d) were quantified in plasma from normolipidaemic control (no MIg or xanthoma) (n = 8, open bars), NXG (n = 8, dark bars), NX (n = 8, light grey bars), MIg controls (no MIg or xanthoma) (dark grey bars) and xanthoma controls (FH patients without MIg and with xanthoma) (n = 7, hatched bars) individuals as determined on a semi-automated biochip array analyzer (Randox). *P < 0.05, **P < 0.005 and ***P <0.0005 versus control plasma. Amounts of ADAM17 (h) or CCR2 (i) mRNA in freshly isolated CD14-positive monocytes from control (n = 9), NX (n = 6) and NXG (n = 4) subjects. *P < 0.05 relative to the control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig04: Patients with NX and NXG exhibit a unique inflammatory pattern. Circulating levels of cytokines (a–b, e, f and g), soluble receptors (c) and adhesion molecules (d) were quantified in plasma from normolipidaemic control (no MIg or xanthoma) (n = 8, open bars), NXG (n = 8, dark bars), NX (n = 8, light grey bars), MIg controls (no MIg or xanthoma) (dark grey bars) and xanthoma controls (FH patients without MIg and with xanthoma) (n = 7, hatched bars) individuals as determined on a semi-automated biochip array analyzer (Randox). *P < 0.05, **P < 0.005 and ***P <0.0005 versus control plasma. Amounts of ADAM17 (h) or CCR2 (i) mRNA in freshly isolated CD14-positive monocytes from control (n = 9), NX (n = 6) and NXG (n = 4) subjects. *P < 0.05 relative to the control.
Mentions: Serum CRP levels were slightly elevated in patients with NXG and NX (7.96 ± 3.48 and 5.77 ± 2.65 mg L−1, respectively) (Table2). Circulating inflammatory cytokines and adhesion molecules were quantified using biochip arrays (Fig.4). Results were compared with data obtained with plasma from both normolipidaemic controls with or without MIg and patients with FH who had xanthoma and high plasma cholesterol levels but no detectable monoclonal gammopathy. In patients with NX and NXG, a marked increase in the plasma levels of pro-inflammatory cytokines (TNFα and IL-6) (Figs4b), soluble cytokine receptors (sIL-6R, sTNFRI and sTNFRII) (Fig.4c) and adhesion molecules (VCAM-1 and ICAM-1) (Fig.4d) was observed relative to all control groups. Levels of the plasma chemokines MCP-1, MIP-1α and IL-8 were also elevated in patients with NX and NXG. A similar increase in MCP-1 and IL-8 levels was also observed in normolipidaemic controls with MIg (Fig.4e). Although patients with NX displayed an overlapping pro-inflammatory pattern with patients with NXG, some differences were detected. For example, the NXG pattern was distinguished by an increase in plasma IL-15 levels (+62%, P < 0.05) (Fig.4f), whilst the NX pattern was characterized by an elevation of both plasma IFNγ and EGF levels (2.4- and 4.4-fold, respectively, P < 0.05) (Figs4a, e). Of note, plasma IFNγ levels were positively correlated with EGF levels in patients with NX and NXG (r = −0.412, P < 0.05).

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