Immunogenetic Heterogeneity in Single-System and Multisystem Langerhans Cell Histiocytosis

Neuropsychological sequelae in patients with neurodegenerative Langerhans cell histiocytosis

“…Our preliminary hypothesis is that LCH is an adverse immune reaction, maybe associated with defect antigen presentation 28. Langerhans cells in LCH have a deficient function 29, and we have previously shown a correlation between the LCH subtypes and the HLA‐system 30. Moreover, we have also shown that patients with CNS‐LCH may have markedly increased 18‐FDG uptake on positron emission tomography compatible with an inflammatory reaction 31, which also is line with neuropathological studies 12.…”

Specific polymorphisms of cytokine genes are associated with different risks to develop single‐system or multi‐system childhood Langerhans cell histiocytosis

“…McClain et al (2003) showed that patients presenting with single bone disease had a particularly high frequency of the HLA‐DR4 allele and, in this group, every Caucasian patient had either the HLA‐Cw7 or DR4 allele. In another independent study of Nordic patients, those with SS disease more often had the allele HLA‐DRB1*03 (Bernstrand et al , 2003). Altogether these data suggest an immunogenetic heterogeneity.…”

Identical twin brothers concordant for Langerhans? cell histiocytosis and discordant for Epstein-Barr virus-associated haemophagocytic syndrome

“…However, CD1a+ histiocytes express also MHC class 1 molecules, and are able to produce an array of cytokines including tumour necrosis factor-a, interferon-c and granulocyte-macrophage colony-stimulating factor [7]. Although the normal Langerhans cell belongs to the dendritic antigen-presenting cells expressing both class 1 and 2 molecules, the antigen-presenting functional capacity of Langerhans cells seem reduced in LCH may explain the finding of macrophage activation with or without haemophagocytosis [4,5]. The association of LCH with HS is not rare and may have even gone underdiagnosed for a number of patients, unless such a condition was specifically sought for [7].…”