SIRPA mutation or changes of its expression level is not involved in pathogenesis of HLH. (A) Sequence alignment of SIRPA IgV domains (exon 3 of SIRPA) identified by sequence analysis from genomic DNA of 50 healthy donors. Two variants, which we have described previously,²⁰  were identified in the present study. There are 13 amino acid differences between these 2 variants. (B) Distribution of genotype of SIRPA IgV domains in 50 healthy donors. PCR products were cloned to pCR 2.1-TOPO vector and 10-25 clones were sequenced for every sample: 24 were heterozygous for variants 1 and 2, 4 were homozygous for variant 1, and 22 were homozygous for variant 2. (C) Distribution of genotype of SIRPA IgV domains in 15 HLH patients (unique patient number [UPN] 1-15); 4 (UPN 2, 4, 7, and 14) were heterozygous of variants 1 and 2, 6 (UPN 3, 5, 8, 10, 11, and 12) were homozygous for variant 1, and 5 (UPN 1, 6, 9, 13, and 15) were homozygous for variant 2. There were no other variants or changes of SIRPA IgV domain in HLH patients. (D) Representative expression of surface SIRPA on CD14⁺ cells of control and HLH patients on FACS. There was no significant difference in the expression level of SIRPA in CD14⁺ monocytes between HLH and normal BM: The mean ± SD of CD47 fluorescence intensity was 116 ± 1.7 and 118 ± 9.6 in healthy controls (n = 5) and HLH patients (n = 5), respectively (P = .88).