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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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Clinical aspects of patients with NX and NXG. (a) Patients NX1, (b) NX5, (c) NX7, (d) NXG7 and (e–f) NXG8.
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fig01: Clinical aspects of patients with NX and NXG. (a) Patients NX1, (b) NX5, (c) NX7, (d) NXG7 and (e–f) NXG8.

Mentions: Patients with NX (n = 8; 3 female patients and five male patients) or NXG (n = 8; 6 female patients and two male patients) were diagnosed between 2004 and 2011. At the time of the study, subjects were between 37 and 82 years of age for NX, and 60 and 83 years of age for NXG. The mean ages were 62 ± 5.8 and 68.8 ± 2.4 years for NX and NXG subjects, respectively. Xanthoma lesions, as identified by histological examination, contained foam-cell infiltration or necrobiosis, cholesterol clefts and Touton giant cells in both NX and NXG (Fig.1). All patients had serum MIg, as was detected by electrophoresis and confirmed by immunofixation (IF). The MIg isotype (IgG, 6 κ and 10 λ), hypocomplementaemia and underlying haematological conditions (MGUS, n = 9; multiple myeloma, n = 6; and lymphoma, n = 1) are detailed in Table1. A diagnosis of atherosclerosis was retained if patients had a cardiovascular event in their background, including stroke, arteriopathy or ischaemic cardiopathy, or during follow-up. Arterial Doppler evaluation was also considered when available (n = 5) (Table1). No patient suffered from obesity, arterial hypertension or insulin resistance that might suggest a metabolic syndrome 12. Test subjects were compared with three groups of control subjects: (i) sex- and age-matched individuals with negative serum IF and no xanthoma lesions (normal controls, n = 8), (ii) sex- and age-matched individuals with detectable serum MIg and no xanthoma lesions (MIg controls, n = 5) and (iii) individuals with familial hypercholesterolaemia (FH) who exhibit xanthoma but not MIg and were homozygous (n = 3), heterozygous (n = 2) or doubly heterozygous (n = 2) for point mutations in the LDLR and/or APOB genes (xanthoma controls, Table S1) 13. Only patients with FH received lipid-lowering drugs and regularly underwent LDL apheresis at intervals of 2–3 weeks. Blood samples from FH patients were collected 2–3 weeks after LDL apheresis and just prior to undergoing a subsequent apheresis. In all cases, blood samples were collected by venipuncture from the antecubital vein into sterile EDTA-containing tubes (final EDTA concentration, 1 mg mL−1). Plasma was separated immediately by low-speed centrifugation at 2500 rpm for 20 min at 4 °C and stored at −80 °C until use. The study protocol was approved by the Saint-Louis Hospital Ethic Committee, and the study was conducted in accordance with the ethical principles set forth in the Declaration of Helsinki. Written informed consent was obtained from all patients.


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)

Clinical aspects of patients with NX and NXG. (a) Patients NX1, (b) NX5, (c) NX7, (d) NXG7 and (e–f) NXG8.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig01: Clinical aspects of patients with NX and NXG. (a) Patients NX1, (b) NX5, (c) NX7, (d) NXG7 and (e–f) NXG8.
Mentions: Patients with NX (n = 8; 3 female patients and five male patients) or NXG (n = 8; 6 female patients and two male patients) were diagnosed between 2004 and 2011. At the time of the study, subjects were between 37 and 82 years of age for NX, and 60 and 83 years of age for NXG. The mean ages were 62 ± 5.8 and 68.8 ± 2.4 years for NX and NXG subjects, respectively. Xanthoma lesions, as identified by histological examination, contained foam-cell infiltration or necrobiosis, cholesterol clefts and Touton giant cells in both NX and NXG (Fig.1). All patients had serum MIg, as was detected by electrophoresis and confirmed by immunofixation (IF). The MIg isotype (IgG, 6 κ and 10 λ), hypocomplementaemia and underlying haematological conditions (MGUS, n = 9; multiple myeloma, n = 6; and lymphoma, n = 1) are detailed in Table1. A diagnosis of atherosclerosis was retained if patients had a cardiovascular event in their background, including stroke, arteriopathy or ischaemic cardiopathy, or during follow-up. Arterial Doppler evaluation was also considered when available (n = 5) (Table1). No patient suffered from obesity, arterial hypertension or insulin resistance that might suggest a metabolic syndrome 12. Test subjects were compared with three groups of control subjects: (i) sex- and age-matched individuals with negative serum IF and no xanthoma lesions (normal controls, n = 8), (ii) sex- and age-matched individuals with detectable serum MIg and no xanthoma lesions (MIg controls, n = 5) and (iii) individuals with familial hypercholesterolaemia (FH) who exhibit xanthoma but not MIg and were homozygous (n = 3), heterozygous (n = 2) or doubly heterozygous (n = 2) for point mutations in the LDLR and/or APOB genes (xanthoma controls, Table S1) 13. Only patients with FH received lipid-lowering drugs and regularly underwent LDL apheresis at intervals of 2–3 weeks. Blood samples from FH patients were collected 2–3 weeks after LDL apheresis and just prior to undergoing a subsequent apheresis. In all cases, blood samples were collected by venipuncture from the antecubital vein into sterile EDTA-containing tubes (final EDTA concentration, 1 mg mL−1). Plasma was separated immediately by low-speed centrifugation at 2500 rpm for 20 min at 4 °C and stored at −80 °C until use. The study protocol was approved by the Saint-Louis Hospital Ethic Committee, and the study was conducted in accordance with the ethical principles set forth in the Declaration of Helsinki. Written informed consent was obtained from all patients.

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