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Physiopathology of necrobiotic xanthogranuloma with monoclonal gammopathy.
J Intern Med. 2014 Sep; 276(3):269-84.JI

Abstract

RATIONALE

Xanthomatosis associated with monoclonal gammopathy includes hyperlipidaemic xanthoma (HX), normolipidaemic xanthoma (NX) and necrobiotic xanthogranuloma (NXG). All three pathologies are characterized by skin or visceral lesions related to cholesterol accumulation, monoclonal immunoglobulin (MIg) and hypocomplementemia. The pathophysiology underlying NXG remains unknown although the involvement of MIg is suspected.

OBJECTIVE

To provide further insights into the pathophysiology of NXG, we evaluated the plasma lipid phenotype, mechanisms involved in cellular cholesterol accumulation and role of MIg in an analysis of blood and plasma markers of inflammation in 16 patients with xanthomatosis [NXG (n = 8) and NX (n = 8)] associated with monoclonal IgG relative to the relevant controls.

RESULTS

The lipid profile of patients with NXG was characterized by a low HDL-C phenotype and an abnormal distribution of HDL particles. Sera from patients with NXG induced cholesterol accumulation in human macrophages. 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. The MIg of NXG and NX patients was tested positively by ELISA to recognize a large spectrum of lipoproteins. High plasma levels of pro-inflammatory cytokines (TNFα and IL-6), soluble cytokine receptors (sIL-6R, sTNFRI and sTNFRII), adhesion molecules (VCAM-1 and ICAM-1) and chemokines (MCP-1, IL-8 and MIP-1α) were observed in both patients with NXG and NX, revealing a specific xanthoma inflammatory signature which was inversely correlated with plasma levels of anti-inflammatory HDL. However, patients with NXG were distinguished by elevated levels of IL-15 and a marked increase in the rate of intermediate CD14++CD16+ monocytes.

CONCLUSION

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.

Authors+Show Affiliations

Département d'immunologie Clinique, Hôpital Saint Louis, Paris, France; EA3963, Université Paris 7 Denis Diderot, INSERM, IFR105, Institut Universitaire d'Hématologie, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24428816

Citation

Szalat, R, et al. "Physiopathology of Necrobiotic Xanthogranuloma With Monoclonal Gammopathy." Journal of Internal Medicine, vol. 276, no. 3, 2014, pp. 269-84.
Szalat R, Pirault J, Fermand JP, et al. Physiopathology of necrobiotic xanthogranuloma with monoclonal gammopathy. J Intern Med. 2014;276(3):269-84.
Szalat, R., Pirault, J., Fermand, J. P., Carrié, A., Saint-Charles, F., Olivier, M., Robillard, P., Frisdal, E., Villard, E. F., Cathébras, P., Bruckert, E., Chapman, M. J., Giral, P., Guerin, M., Lesnik, P., & Le Goff, W. (2014). Physiopathology of necrobiotic xanthogranuloma with monoclonal gammopathy. Journal of Internal Medicine, 276(3), 269-84. https://doi.org/10.1111/joim.12195
Szalat R, et al. Physiopathology of Necrobiotic Xanthogranuloma With Monoclonal Gammopathy. J Intern Med. 2014;276(3):269-84. PubMed PMID: 24428816.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Physiopathology of necrobiotic xanthogranuloma with monoclonal gammopathy. AU - Szalat,R, AU - Pirault,J, AU - Fermand,J-P, AU - Carrié,A, AU - Saint-Charles,F, AU - Olivier,M, AU - Robillard,P, AU - Frisdal,E, AU - Villard,E F, AU - Cathébras,P, AU - Bruckert,E, AU - Chapman,M John, AU - Giral,P, AU - Guerin,M, AU - Lesnik,P, AU - Le Goff,W, Y1 - 2014/02/10/ PY - 2014/1/17/entrez PY - 2014/1/17/pubmed PY - 2014/9/30/medline KW - HDL KW - histiocytes KW - immune complex KW - monoclonal immunoglobulin KW - monocyte KW - necrobiotic xanthogranuloma SP - 269 EP - 84 JF - Journal of internal medicine JO - J. Intern. Med. VL - 276 IS - 3 N2 - RATIONALE: Xanthomatosis associated with monoclonal gammopathy includes hyperlipidaemic xanthoma (HX), normolipidaemic xanthoma (NX) and necrobiotic xanthogranuloma (NXG). All three pathologies are characterized by skin or visceral lesions related to cholesterol accumulation, monoclonal immunoglobulin (MIg) and hypocomplementemia. The pathophysiology underlying NXG remains unknown although the involvement of MIg is suspected. OBJECTIVE: To provide further insights into the pathophysiology of NXG, we evaluated the plasma lipid phenotype, mechanisms involved in cellular cholesterol accumulation and role of MIg in an analysis of blood and plasma markers of inflammation in 16 patients with xanthomatosis [NXG (n = 8) and NX (n = 8)] associated with monoclonal IgG relative to the relevant controls. RESULTS: The lipid profile of patients with NXG was characterized by a low HDL-C phenotype and an abnormal distribution of HDL particles. Sera from patients with NXG induced cholesterol accumulation in human macrophages. 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. The MIg of NXG and NX patients was tested positively by ELISA to recognize a large spectrum of lipoproteins. High plasma levels of pro-inflammatory cytokines (TNFα and IL-6), soluble cytokine receptors (sIL-6R, sTNFRI and sTNFRII), adhesion molecules (VCAM-1 and ICAM-1) and chemokines (MCP-1, IL-8 and MIP-1α) were observed in both patients with NXG and NX, revealing a specific xanthoma inflammatory signature which was inversely correlated with plasma levels of anti-inflammatory HDL. However, patients with NXG were distinguished by elevated levels of IL-15 and a marked increase in the rate of intermediate CD14++CD16+ monocytes. CONCLUSION: 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. SN - 1365-2796 UR - https://www.unboundmedicine.com/medline/citation/24428816/Physiopathology_of_necrobiotic_xanthogranuloma_with_monoclonal_gammopathy_ L2 - https://doi.org/10.1111/joim.12195 DB - PRIME DP - Unbound Medicine ER -