Langerhans cell histiocytosis patients have HLA Cw7 and DR4 types associated with specific clinical presentations and no increased frequency in polymorphisms of the tumor necrosis factor alpha promoter

McClain, Kenneth L.; Laud, Purnima R.; Wu, Wen Shu; Pollack, Marilyn S.

doi:10.1002/mpo.10366

Cited by 18 publications

(9 citation statements)

References 32 publications

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“…Of over 900 patients seen at the Texas Children’s Histiocytosis Clinic, there have been only one family with nontwin sibling LCH patients and one with a parent and child both having LCH. While it remains plausible that potential risk alleles such as tumor necrosis factor gene promoter polymorphisms (McClain, Laud, Wu, & Pollack, 2003) or exposures such as parental occupational exposure to metal (Jubran, Marachelian, Dorey, & Malogolowkin, 2005) may be shared by siblings, Mendelian inheritance of penetrant LCH “genes” in the majority of cases seems unlikely. Additional reported associations from family studies that may inform LCH pathogenesis include increased risk of other cancers in LCH patients (Egeler et al, 1998) and increased risk of family history of thyroid disease (Bhatia et al, 1997).…”

Section: Human Histiocytoses As a Results Of Dysregulated Differenmentioning

confidence: 99%

Pathological Consequence of Misguided Dendritic Cell Differentiation in Histiocytic Diseases

Berres

Allen

Mérad

2013

Advances in Immunology

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Histiocytic disorders represent a group of complex pathologies characterized by the accumulation of histiocytes, an old term for tissue-resident macrophages and dendritic cells. Langerhans cell histiocytosis is the most frequent of histiocytosis in humans and has been thought to arise from the abnormal accumulation of epidermal dendritic cells called Langerhans cells. In this chapter, we discuss the origin and differentiation of Langerhans cells and dendritic cells and present accumulated evidence that suggests that Langerhans cell histiocytosis does not result from abnormal Langerhans cell homeostasis but rather is a consequence of misguided differentiation programs of myeloid dendritic cell precursors. We propose reclassification of Langerhans cell histiocytosis, juvenile xanthogranuloma, and Erdheim–Chester disease as inflammatory myeloid neoplasias.

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Section: Human Histiocytoses As a Results Of Dysregulated Differenmentioning

confidence: 99%

Pathological Consequence of Misguided Dendritic Cell Differentiation in Histiocytic Diseases

Berres

Allen

Mérad

2013

Advances in Immunology

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“…CCL20/MIP3α (51), CCL5/RANTES (51), CCR6 (51), CD40LG (39,61,74), CXCR3 (10), FOXP3 (32), GMCSF/CSF2 (10,69,70), HLA-DR/DQ (10,39,80), IFN-γ (10,23,24), IL-10 (10,32,39), IL-17A (22), IL-1R1 (75), IL-1α (10,23,24), IL-1β (10,23,24), IL-2 (10,23,24), IL-22 (22), IL2Rα/CD25 (32,74), IL-3 (10,24), IL-4 (10,23,24), IL-5 (10,24), (IL-6) 10, TGF-β (10,23,24), TNFRSF11B (74,75), TNFSF11/RANKL (22,74), TNFα (10,24,25,79). …”

Section: Figurementioning

confidence: 99%

Cell-Specific Gene Expression in Langerhans Cell Histiocytosis Lesions Reveals a Distinct Profile Compared with Epidermal Langerhans Cells

Allen

Peters³

et al. 2010

The Journal of Immunology

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278

272

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Langerhans-cell histiocytosis (LCH) is a rare disease characterized by heterogeneous lesions containing CD207+ Langerhans cells and lymphocytes that can arise in almost any tissue and cause significant morbidity and mortality. After decades of research, the cause of LCH remains speculative. A prevailing model suggests that LCH arises from malignant transformation and metastasis of epidermal Langerhans cells. In this study, CD207+ cells and CD3+ T cells were isolated from LCH lesions to determine cell-specific gene expression. Compared to control epidermal CD207+ cells, the LCH CD207+ cells yielded 2113 differentially-expressed genes (FDR<0.01). Surprisingly, expression of many genes previously associated with LCH, including cell-cycle regulators, pro-inflammatory cytokines and chemokines were not significantly different from control LCs in our study. However, several novel genes whose products activate and recruit T cells to sites of inflammation, including SPP1 (osteopontin), were highly over-expressed in LCH CD207+ cells. Furthermore, several genes associated with immature myeloid dendritic cells were over-expressed in LCH CD207+ cells. Compared to the peripheral CD3+ cells from LCH patients, the LCH lesion CD3+ cells yielded only 162 differentially-regulated genes (FDR<0.01), and the expression profile of the LCH lesion CD3+ cells was consistent with an activated regulatory T cell phenotype with increased expression of FOXP3, CTLA4 as well as SPP1. Results from this study support a model of LCH pathogenesis in which lesions do not arise from epidermal Langerhans cells, but from accumulation of bone-marrow derived immature myeloid dendritic cells that recruit activated lymphocytes.

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“…Markedly elevated levels of FLT3-ligand and M-CSF have been found in the serum of LCH patients, showing good correlations with the extent of disease and response to treatment [24]. Specific associations of LCH with HLA types and the extent of disease have been published [25,26]. Increased chromosomal breakage in peripheral blood lymphocytes stimulated with phytohaemagglutinin has been reported [27].…”

Section: The Langerhans Cellmentioning

confidence: 93%

“…As an example, in the Mayo Clinic series of children and adults, 42 of 44 patients with DI had involvement of other organ systems: bone (68%), skin (57%), lung (39%) and lymph nodes (18%) [26].…”

Section: Endocrine Disordersmentioning

confidence: 99%

Langerhans cell histiocytosis

Blesa

Candel

Vercet³

et al. 2008

Clin Transl Oncol

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Langerhans cell histiocytosis (LCH) is a poorly understood proliferative disease, with different patterns of clinical presentation. Currently it is classified according to the number and type of system involved and the degree of organ dysfunction. The aetiology of the disease remains uncertain, and in some cases the disease is polyclonal, suggesting a reactive condition. Many cytokines have been implicated in the pathogenesis of LCH. Different therapeutic approaches can be considered depending on the affected organ, including surgery, radiotherapy and chemotherapy. Long-term organ dysfunction may remain, despite disease control and/or eradication, making indefinite supportive treatment mandatory. Here we present a literature review on all of the aspects of the disease, treatment approaches and existing protocols, and finally an adult clinical case.

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Langerhans cell histiocytosis patients have HLA Cw7 and DR4 types associated with specific clinical presentations and no increased frequency in polymorphisms of the tumor necrosis factor alpha promoter

Cited by 18 publications

References 32 publications

Pathological Consequence of Misguided Dendritic Cell Differentiation in Histiocytic Diseases

Pathological Consequence of Misguided Dendritic Cell Differentiation in Histiocytic Diseases

Cell-Specific Gene Expression in Langerhans Cell Histiocytosis Lesions Reveals a Distinct Profile Compared with Epidermal Langerhans Cells

Langerhans cell histiocytosis

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