Anti-CD207 Monoclonal antibody, clone M42 [Biotin]

Langerhans cell histiocytosis (LCH) is a clonal disorder with elusive etiology, characterized by the accumulation of CD207(+) dendritic cells (DCs) in inflammatory lesions. Recurrent BRAF-V600E mutations have been reported in LCH. In this study, lesions from 100 patients were genotyped, and 64% carried the BRAF-V600E mutation within infiltrating CD207(+) DCs. BRAF-V600E expression in tissue DCs did not define specific clinical risk groups but was associated with increased risk of recurrence. Strikingly, we found that patients with active, high-risk LCH also carried BRAF-V600E in circulating CD11c(+) and CD14(+) fractions and in bone marrow (BM) CD34(+) hematopoietic cell progenitors, whereas the mutation was restricted to lesional CD207(+) DC in low-risk LCH patients. Importantly, BRAF-V600E expression in DCs was sufficient to drive LCH-like disease in mice. Consistent with our findings in humans, expression of BRAF-V600E in BM DC progenitors recapitulated many features of the human high-risk LCH, whereas BRAF-V600E expression in differentiated DCs more closely resembled low-risk LCH. We therefore propose classification of LCH as a myeloid neoplasia and hypothesize that high-risk LCH arises from somatic mutation of a hematopoietic progenitor, whereas low-risk disease arises from somatic mutation of tissue-restricted precursor DCs.

Background: Multi-ancestry genome-wide association study (GWAS) has recently identified 11 new susceptibility loci for Atopic dermatitis (AD). The replication of these new susceptibility loci in different populations should not be ignored. Objective: To examine whether these 11 new identified susceptibility loci are also associated with AD in the Chinese Han population. Methods: These 11 variants were imputed using our genome-wide array dataset. The selected SNPs with suggestive signals were genotyped in a large-scale replication study with a total of 4619 cases and 10,789 controls using the Sequenom Massarray system. Association analyses were performed using PLINK 1.07 software. Results were combined across our previous AD-GWAS stage and the replication stage by meta-analysis. Bioinformatic analysis was done to predict the possible causal gene. Results: Of the 11 SNPs investigated, four SNPs showed suggestive association (P < 0.05) in our previously published GWAS datasets. Association evidence for an intergenic variant rs112111458 at 2p13.3 with AD was replicated in Chinese Han population (P = 7.37 x 10(-7), OR = 0.86), showing significance in Meta analysis of GWAS and replication study (P-meta = 8.18 x 10(-08), OR = 0.69). Further functional annotation by HaploReg indicated that transcriptional regulation activity exists at this locus for the CD207 gene in skin tissue. Conclusions: Our study confirmed a previously reported susceptibility loci in the Chinese Han population, which implicates CD207 might be a new susceptibility gene for AD and highlights the crucial role of immune responses in AD.