Immune deficiencies, infection, and systemic immune disordersHaploinsufficiency of TNFAIP3 (A20) by germline mutation is involved in autoimmune lymphoproliferative syndrome
Section snippets
Cell culture
Control and patient-derived PBMCs were cultured as activated T cells. PBMCs were stimulated with anti-CD2, anti-CD3, and anti-CD28 beads, according to the manufacturer's protocol (Miltenyi Biotec, Gladbach, Germany), and expanded with ALyS505N-0 Medium (Cell Science & Technology Institute, Miyagi, Japan) supplemented with 10% FBS and 50 g/mL recombinant human IL-2 (PeproTech, Rocky Hill, NJ).
Genome analysis
Genomic analysis was performed after obtaining informed consent from each patient. The genetic analysis
Case description
A 7-month-old Japanese boy had a fever and was found to have increased levels of C-reactive protein. The patient was treated with antibiotics, which had no significant effect. After spontaneous resolution of the fever, liver dysfunction was transiently observed for 2 months. The patient presented to the hospital at 1 year of age with fever, cervical lymph node swelling, and skin rash. Bilateral cervical lymphadenopathy and hepatosplenomegaly were noted (Fig 1, A and B). Because the fever
Discussion
TNFAIP3 (A20) heterozygous knockout mice appear normal without evidence of pathology; however, TNFAIP3 (A20) homozygous knockout mice show severe inflammation, are hypersensitive to both LPS and TNF, and die prematurely.22 The human TNFAIP3 (A20) locus and its polymorphisms are associated with certain conditions, such as Crohn disease, rheumatoid arthritis, systemic lupus erythematosus, psoriasis, and type 1 diabetes.23 These findings further illustrate the importance of TNFAIP3 (A20) in the
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Supported by a Grant-in-Aid for Research on Measures for Intractable Diseases from the Japan Agency for Medical Research and Development (AMED), 27280301 and 26070201.
Disclosure of potential conflict of interest: M. Takagi and S. Ogawa receive research support from a Grant-in-Aid for Research on Measures for Intractable Diseases from the Japan Agency for Medical Research and Development. The rest of the authors declare that they have no relevant conflicts of interest.
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These authors contributed equally to this work.