Fig 1.
Flow of idiopathic hypereosinophilia study.
Flow diagram showing how patients were included and evaluated in this study.
Fig 2.
Workflow of filtering variants for the detection of candidate mutations.
Flowchart shows the pipeline we used for filtering variants. Following exclusion of low quality variants (<20x total reads or <10 allele counts), synonymous, noncoding variants and polymorphisms were discarded. When recurrently reported in COSMIC V60 database, the variants were rescued.
Fig 3.
Distribution of mutated genes in idiopathic hypereosinophilia patients.
The frequency of candidate mutations in each gene was listed for the all 16 patients with mutation positive.
Fig 4.
Correlations between frequently mutated genes (more than 2 patients).
Statistically significant correlations (P < 0.05) were indicated. The correlation coefficients are shown by a color gradient and size difference.
Fig 5.
An illustration indicating action levels of discovered genes in the present study in relation to eosinophil production and Pathway Studio network analysis.
Networks were created based on at least one published reference regarding candidate genes and the known 14 genes related to eosinophil production. (A) Genes marked with blue letter are well-known genes for which mechanisms are proven in eosinophil production. (B) Genes exerting on eosinophil lineage commitment at hematopoietic stem cell level. (C) Genes exerting at eosinophil lineage commitment and prolongation of eosinophil survival. (D) Eosinophil recruitment into tissue. (E) Genes interacting with IL-5, pivotal to eosinophil production and differentiation. GATA1 and CEBPA were excluded from the network because they are involved in both eosinophil lineage commitment and the candidate gene set.
Fig 6.
Mutation profiles and clinical features of patients with TCR rearrangement.
(A) The incidence of mutations (n = 16) and clonal TCR rearrangements (n = 4) in IHE or IHES samples. Only one sample out of four clonal TCR rearrangement samples concurrently harbored somatic mutation. (B) Rate of skin involvement in IHE or IHES patients with or without clonal TCR rearrangement.
Table 1.
Mutated genes in patients with eosinophilia (n = 16).
Fig 7.
Dysplastic eosinophils frequently observed in IHE/IHES patients harboring mutations (n = 7).
Cytoplasms are filled with abnormal secondary basophilic granules (BM, Wright-Giemsa, 1000×). Dysplastic eosinophils were more common in the mutation-positive group than in the mutation-negative group (P = 0.045).
Table 2.
Patient clinical characteristics according to somatic mutation status.