Patient 3 was a 24-year-old woman. She had suffered from athetoid cerebral palsy due to cardiopulmonary arrest of unknown cause on postnatal day 1. She had developed epilepsy at the age of 4 years and type 1 diabetes with positive anti-glutamic acid decarboxylase antibody at the age of 12 years. At the age of 24 years, she had a fever, facial erythema, and proteinuria. She was diagnosed with systemic lupus erythematosus (SLE) with the following findings: positive antinuclear antibodies, anti-dsDNA antibodies, anti-Sm antibodies, anti-cardiolipin antibodies, hypocomplementemia, and positive direct Coombs test. She had a heterozygous c.2126A>G (p.Gln709Arg) variant of TNFAIP3. Her father had the same variant but lacked any symptoms.\nThe variant Glu192Lys was identified among 55 patients suspected of having autoinflammatory diseases analyzed at Gifu University Hospital from October 2017 to September 2020. The patients with variants Ile310Thr and Gln709Arg were recruited by personal communication with the collaborators (Nagasaki University and Tokyo Medical and Dental University).\nWritten informed consent to participate in this study was obtained from each of the patients or their parents. This study was conducted in accordance with the Declaration of Helsinki and approved by the ethics boards of Gifu University and Tokyo Medical and Dental University.
The patient was a 29-year-old female who had suffered from recurrent oral ulcers, abdominal pain and diarrhea since the age of 15 years. Recurrent ascending colonic ulcers and anastomotic ulcers along with intestinal obstruction were observed prior to and for 8 years after right hemicolectomy surgery (), accompanied by vasculitis in extremities (). Laboratory data showed elevated C-reactive protein (19.6 mg/L; normal range (NR) <5 mg/L) and erythrocyte sedimentation rate (25 mm/h; NR<20 mm/h), along with a low titer of the antinuclear antibody (1:100). Serum IgG and IgM were within the normal range but IgA levels were low (IgG 19.3–25.8g/L, IgM 0.73–0.92 g/L, IgA <0.07g/L). The patient responded to a glucocorticoid and thalidomide in 3 months with reduced frequency of diarrhea and less severe abdominal pain. The patient's IgA increased but did not reach normal levels after treatment. Subsequent inquiries into the patient's family history revealed that her father suffered from recurrent oral ulcers when he was young, and her brother had suffered from recurrent fever, oral ulcers and erythema nodosum-like lesions in the skin since he was 4 years old. The level of serum immunoglobulins in the father and brother were in the normal ranges. Because of the mild and non-specific symptoms, they accepted treatment of only antimicrobial mouthwash and dental ulcer paste instead of immunomodulators.