IntroductionOmenn syndrome (OS) is a peculiar immunodeficiency characterized by erythroderma, lymphadenopathy, hepatosplenomegaly, eosinophilia, hypogammaglobulinemia, elevated serum IgE, and activated/oligoclonal T cells. 1,2 The genes responsible for OS include RAG1, RAG2, Artemis, RMRP, and IL7RA. [3][4][5][6][7][8] Clinical manifestations resembling OS were demonstrated in cases of severe combined immunodeficiency (SCID) with maternal T-cell engraftment and of atypical DiGeorge syndrome. 9,10 In addition, we have recently reported an X-linked SCID (XSCID) patient with massive skin infiltration of natural killer (NK) cells, resulting in OS-like manifestations. 11 Here, we describe another case of XSCID mimicking OS. The patient carried a splice site mutation that allowed development of peripheral T and NK cells, and showed revertant T-cell mosaicism caused by a second-site mutation predominately in the skin. Both of these findings may have contributed to his phenotypic variation of XSCID.
Methods
PatientA 5-month-old Japanese boy from nonconsanguineous parents was hospitalized because of failure to thrive, protracted diarrhea, and hypoproteinemia. He developed generalized erythematous rash and alopecia at 1 month of age ( Figure 1A,B), followed by persistent cough, fever, hepatosplenomegaly, and lymphadenopathy. Laboratory studies revealed leukocytosis (60.0 ϫ 10 9 /L) with eosinophilia, liver dysfunction, and a low level of serum immunoglobulin G (IgG; 0.17 g/L). Serum IgE levels were significantly elevated at 1300 kIU/L. Immunophenotypic analysis of lymphocytes showed an increased percentage of CD3 ϩ T cells (93.1%), the majority expressing the activation markers CD45RO and HLA-DR. The ratio of CD4 ϩ to CD8 ϩ T cells was 1.1. The patient's CD20 ϩ B and CD56 ϩ NK cells were detectable at 3.8% and 3.2%, restrictively. The level of soluble interleukin-2 receptor was markedly elevated at 10 895 kIU/L. He had a normal thymus shadow. A skin biopsy exhibited massive lymphocytic infiltration and mild spongiosis ( Figure 1C,D). His maternal half-brother died of interstitial pneumonia at infancy.
Cellular and molecular studiesCell isolation, fluorescence-activated cell sorting (FACS) analysis for the common gamma chain (␥c) and T-cell receptor (TCR) repertoire, spectratyping, microsatellite analysis, and mutation analysis of ␥c were performed as described elsewhere. [11][12][13][14][15] The purity of the sorted CD4 ϩ T, CD8 ϩ T, CD19 ϩ B, and CD56 ϩ NK cells was 98.1%, 99.3%, 86.4%, and 98.3%, respectively. T-cell and B-cell lines from the patient were established by transformation with Herpes virus saimiri and Epstein-Barr virus, respectively. Approval for the study was obtained from the Human Research Committee of Kanazawa University Graduate School of Medical Science, and informed consent was obtained in accordance with the Declaration of Helsinki.
Results and discussionThe patient's clinical findings were reminiscent of OS. However, he showed neither mutation in the RAG genes (data not shown) nor severely restric...
