A20 Haploinsufficiency Presenting with a Combined Immunodeficiency
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LETTER TO EDITOR
A20 Haploinsufficiency Presenting with a Combined Immunodeficiency Melissa D. Gans 1
&
Hongying Wang 2 & Natalia Sampaio Moura 2 & Ivona Aksentijevich 2 & Arye Rubinstein 1
Received: 22 May 2020 / Accepted: 3 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
To the Editor: A20, encoded by TNFAIP3, is an ubiquitin-editing enzyme that plays a key role in the negative regulation of inflammation and immune responses. A deficiency of A20 leads to increased NF-κB and mitogen-activated protein kinase (MAPK) signaling and uncontrolled NLRP3 inflammasome activation. In 2016, Zhou et al. first described heterozygous germline TNFAIP3 loss-of-function (LOF) variants causing A20 haploinsufficiency (HA20) [1]. To date, there have been over 60 cases with HA20 reported in the literature with heterogeneous presentations and age at onset. Patients with HA20 have an autoinflammatory, Behcet’s-like disease characterized by recurrent oral/genital ulcers, polyarthritis, cutaneous lesions, gastrointestinal complaints, episodic fever, ocular symptoms, cardiovascular involvement, autoimmune features, and/or recurrent infections. Treatment with a variety of immunosuppressant agents has been used in HA20 disease with the most success with interleukin-1β, tumor necrosis factor, and janus kinase (JAK) inhibitors. There have been only a few HA20 patients described with sinopulmonary infections, low IgG, IgG subclass deficiency, lymphopenia, and/or natural killer (NK) cell dysfunction [2, 3]. Here, we describe a patient
who presented with a combined immunodeficiency and systemic inflammation caused by a novel LOF variant in A20. The patient is a 27-year-old male who was referred for a history of recurrent fevers, infections, mouth ulcers, and chronic diarrhea since late childhood. His fevers are associated with night sweats and chills with no specific periodicity. He has a history of recurrent episodes of pneumonia, sinusitis, otitis media and externa, conjunctivitis, viral bronchitis, methicillin-resistant Staphylococcus aureus folliculitis, H. pylori gastritis, oral thrush, dental carries, and longstanding EBV viremia but no hospitalizations for severe infections. He has recurrent mouth and genital ulcers. The patient reports about three watery non-bloody bowel movements daily and has had a normal endoscopy and colonoscopy. He has no history of arthritis, rashes, ocular symptoms besides mild myopia, chest pain, food allergies, or other issues. He has not previously been on any immunomodulatory/ suppressive therapy. On physical exam, he is cachectic (body mass index 16 kg/m2) with splenomegaly, hepatomegaly, coarse breath sounds but no lymphadenopathy, overlapping dentition, and is otherwise well appearing. The patient is Ashkenazi with four healthy children and eight siblings.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10875-020-00823-5) contains supplementary material, which is available to authorized users. * Melissa D. Gans mstone@montef
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