CD47 expression is down-regulated specifically in the CD34⁺CD38⁻ HSC fraction in HLH patients, reflecting the disease activity. (A) CD47 expression of CD34⁺CD38⁻ cells, CD34⁺CD38⁺ cells and unfractionated BM cells in HLH patients and healthy controls. The number in each open circle corresponds to the unique patient number (UPN) of patients (supplemental Table 1). The horizontal bars in each group show mean values of the group. The level of CD47 on CD34⁺CD38⁻ cells was significantly decreased compared with that on CD34⁺CD38⁺ cells and more mature cells. The CD47 expression index represents the relative surface CD47 level (median CD47 levels of analyzed cells/those in normal blood mononuclear cells). (B) Histograms of CD47 expression of BM cells in 4 representative HLH patients (UPN 1, 8, 9, and 12). (C) CD47 expression of CD34⁺CD38⁻ HSC-enriched fraction and of each progenitor cell fraction in HLH patients (UPN 1, 4, 9, and 10) and healthy controls. All progenitor populations expressed equivalent levels of CD47, and CD47 expression was down-regulated only in HSC fraction. (D) Change of CD47 expression in UPN 10 during multiple episodes of HLH. Down-regulation of CD47 repeatedly occurred at exacerbation of HLH.