A rare case of PLCG2-associated antibody deficiency and immune dysregulation associated with a synonymous variant in the PLCG2 gene.

Abstract

Dear Editor, Dominantly inherited variants in the phospholipase C gamma 2 (PLCG2) gene might lead to a spectrum of disorders ranging from allergy and immunodeficiency to autoimmunity and autoinflammation [1], mainly including PLCG2-associated antibody deficiency and immune dysregulation [PLAID; Online Mendelian Inheritance in Man (OMIM) 614468] and autoinflammatory PLCG2-associated antibody deficiency and immune dysregulation (APLAID; OMIM 614878). PLAID is usually characterized by cold urticaria, humoral immune deficiency, cutaneous granulomas and autoimmune disease [2]. Herein we describe a rare case of PLAID phenotype associated with a synonymous variant in the PLCG2 gene. A 56-year-old Han Chinese man presented with recurrent fever for 15 years, accompanied by chilliness, fatigue, myalgia and arthralgia, with each episode lasting 10 days. He also suffered from chronic thyroiditis. There was no chest pain, abdominal pain, conjunctivitis, hearing loss or headache. On examination, we observed keratinized skin rashes on his hands and feet and verruca vulgaris was diagnosed. His father had interstitial lung disease and passed away at age 73 years. His mother died of myocardial infarction at age 60 years (Fig. 1A). Other family members had no similar symptoms. During attack periods, acute phase reactants such as ESR (95.0 mm/h, normal <20.0 mm/h) and CRP (131.92 mg/l, normal <8.00 mg/l) as well as pro-inflammatory cytokines including IL-6 (>1000 pg/ml, normal <5.9 pg/ml) and TNF-α (77.6 pg/ml, normal <8.1 pg/ml) were elevated significantly. His WBC count (12.73 × 109/l, normal 3.50–9.50 × 109/l) and eosinophil count (0.82 × 109/l, normal 0.02–0.50 × 109/l) were also increased. These indicators decreased to normal levels during remission intervals (Fig. 1B). In addition, laboratory examinations showed decreased B lymphocytes (112/μl, normal 180–324/μl), NK cells (168/μl, normal 175–567/μl) and IgG (5.59 g/l, normal 7.00–17.00 g/l), indicating impaired immunological function. Testing for ANA and ANCA was negative. Chest CT images revealed multiple micronodules and scattered calcification in bilateral lungs. Based on the patient’s manifestations and laboratory inspections, tumour, infectious diseases and connective tissue diseases were excluded and autoinflammatory disease was highly suspected.