A case series of Haploinsufficiency of A20 with novel mutations in TNFAIP3

Reference: He, T., Huang, Y., Luo, Y. et al. Haploinsufficiency of A20 Due to Novel Mutations in TNFAIP3. J Clin Immunol (2020).

Journal: Journal of Clinical Immunology

Summary: 1. 6 Chinese patients with heterozygous mutations in TNFAIP3 who presented with early-onset autoimmune/auto-inflammatory features were further evaluated in this study

                   2. The median age of onset was 5 years, all patients had oral and/or genital ulcers. Other common clinical features were short statute, periodic fever, enteropathy, esophageal ulcers arthritis and pulmonary disease like interstitial lung disease

                   3. Laboratory investigations showed elevated ESR,CRP, anemia, lymphopenia, thrombocytosis, reduced C3/C4, and presence of multiple autoantibodies in most cases

                  4. Immunological evaluation revealed reversed CD4/CD8 ratio, elevated IgG/IgA levels, elevated cytokine levels that returned to normal during remission, reduced B cell and naive B cell numbers and low CD4 T helper and T follicular helper cells

                    5. T cells showed increased susceptibility to RICD and FAS mediated apoptosis and increased IkBα degradation

                    6. The patients were managed symptomatically using immunosuppressive therapy

Bottom line: A20 regulates cell apoptosis and necroapotosis as it inhibits NF-kB pathway and the haploinsufficient patients present with diverse clinical manifestation