Genetic characteristics, time course of lymphoma development, and treatment in patients with IL-10R deficiency. (A) Pedigrees of the 5 patients with IL-10R1– and IL-10R2–deficient patients. Consanguinity (double horizontal bars), affected individuals (black boxes and circles), carriers (half-filled boxes and circles), and subjects not available for participation in the study (asterisks) are indicated. P1 carried a homozygous missense mutation in exon 2 (p.Y59C) of the IL-10RB gene. This mutation was absent from genome databases (including HGMD, Ensembl, and 1000 Genomes). P2 was a heterozygous composite with a frameshift mutation in exon 7 (F269fsX275) and a missense mutation in exon 5 (p.W204C) of IL-10RB. P3 carried an homozygous nonsense mutation in exon 3 of IL-10RB (p. E141X, as previously reported by Begue et al⁸ ). P4 displayed homozygous deletion (g.11930-17413 del) in IL-10RB. P5 carried a homozygous c.368-10 C>G mutation in intron 3 of IL-10RA. (B) Positions of the IL-10RA and IL-10RB mutations within the gene sequence. (C) Time course of lymphoma development and treatment. Immunosuppressive treatment with azathioprine is represented as a gray rectangle, and administration of an anti–tumor necrosis factor antibody is shown in blue. Maintenance therapy with 6-mercaptopurine and methotrexate was given in P4 after remission of L3 and is represented by a yellow rectangle. P1 (IL-10R2) died as a result of the progression of EBV-positive Hodgkin-like lymphoproliferative disease (LPD) (despite chemotherapy); P2 (IL-10R2) died of meningoencephalitis (of undetermined etiology) that occurred during chemotherapy; P3 (IL-10R2) was in remission from lymphoma when he received a transplant from a mismatched family donor and is now alive and well 12 months after HSCT; P4 (IL-10R2) was in remission from L4 when he received a transplant from a geno-identical sibling. He is alive and well 18 months after HSCT. P5 (IL-10R1) is in remission from lymphoma and is alive and well 3.4 years after completion of chemotherapy (HSCT is pending). wt, wild-type; yrs, years; occurrence shown by arrows (↓).