{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:20:16Z","timestamp":1785406816886,"version":"3.56.0"},"reference-count":63,"publisher":"Rockefeller University Press","issue":"4","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001245","name":"Jeffrey Modell Foundation","doi-asserted-by":"publisher","award":["Translational Research Grant"],"award-info":[{"award-number":["Translational Research Grant"]}],"id":[{"id":"10.13039\/100001245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006260","name":"Rheumatology Research Foundation","doi-asserted-by":"publisher","award":["R bridge award"],"award-info":[{"award-number":["R bridge award"]}],"id":[{"id":"10.13039\/100006260","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7,6]]},"abstract":"<jats:p>Haploinsufficiency of A20 (HA20) is a primary immune regulation disease caused by heterozygous loss-of-function variants in TNFAIP3, resulting in unchecked inflammatory signaling. HA20 is a highly heterogeneous disorder with overlapping features of autoinflammation, autoimmunity, immunodeficiency, atopy, and lymphoproliferation. Most patients develop symptoms in early childhood mimicking Behcet\u2019s disease, inflammatory bowel disease, periodic fevers with aphthous stomatitis, pharyngitis, and adenopathy (PFAPA), systemic lupus erythematosus (SLE), autoimmune hepatitis, vasculitis, and other conditions. This phenotypic variability contributes to diagnostic delays. Diagnosis requires identification of a pathogenic TNFAIP3 variant or deletion encompassing TNFAIP3: most are null, but missense variant interpretation remains challenging. After diagnosis, we use comprehensive clinical laboratory studies, imaging, and multidisciplinary evaluations to screen for complications. Treatment is guided by clinical phenotype and biomarkers. Colchicine and PDE4 inhibitors may control mild disease, whereas IL-1, TNF, and JAK inhibitors are often necessary for moderate-severe cases. Acute withdrawal of immunosuppression can precipitate disease flares. Genetic counseling and evaluation of at-risk family members are essential.<\/jats:p>","DOI":"10.70962\/jhi.20250138","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T06:22:09Z","timestamp":1774678929000},"update-policy":"https:\/\/doi.org\/10.70962\/jhi.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["How I Treat: Haploinsufficiency of A20"],"prefix":"10.70962","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0916-6678","authenticated-orcid":true,"given":"Jonathan","family":"Li","sequence":"first","affiliation":[{"name":"University of Pittsburgh Medical Center 1 Division of Rheumatology and Clinical Immunology, , Pittsburgh, PA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3683-3448","authenticated-orcid":true,"given":"Jeffrey Y.","family":"Zhou","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Medical Center 2 Division of General Internal Medicine, , Pittsburgh, PA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4199-2814","authenticated-orcid":true,"given":"Manuel","family":"Carpio Tumba","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Medical Center 1 Division of Rheumatology and Clinical Immunology, , Pittsburgh, PA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0222-2091","authenticated-orcid":true,"given":"Tingyan","family":"He","sequence":"additional","affiliation":[{"name":"Autoinflammatory Center of Excellence, University of Pittsburgh Medical Center 3 , Pittsburgh, PA,","place":["USA"]},{"name":"Pittsburgh Immunogenetics Discovery Center, University of Pittsburgh Medical Center 4 , Pittsburgh, PA,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/0409k5a27","id-type":"ROR","asserted-by":"publisher"}],"name":"Shenzhen Children\u2019s Hospital 5 Division of Rheumatology and Immunology, , Shenzhen,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1039-3701","authenticated-orcid":true,"given":"Kader","family":"Cetin Gedik","sequence":"additional","affiliation":[{"name":"Autoinflammatory Center of Excellence, University of Pittsburgh Medical Center 3 , Pittsburgh, PA,","place":["USA"]},{"name":"Pittsburgh Immunogenetics Discovery Center, University of Pittsburgh Medical Center 4 , Pittsburgh, PA,","place":["USA"]},{"name":"University of Pittsburgh Medical Center 6 Division of Pediatric Rheumatology, , Pittsburgh, PA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1660-8438","authenticated-orcid":true,"given":"Daniella M.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Medical Center 1 Division of Rheumatology and Clinical Immunology, , Pittsburgh, PA,","place":["USA"]},{"name":"Autoinflammatory Center of Excellence, University of Pittsburgh Medical Center 3 , Pittsburgh, PA,","place":["USA"]},{"name":"Pittsburgh Immunogenetics Discovery Center, University of Pittsburgh Medical Center 4 , Pittsburgh, PA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"2026050409152300700_bib1","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/ng.3459","article-title":"Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease","volume":"48","author":"Zhou","year":"2016","journal-title":"Nat. Genet."},{"key":"2026050409152300700_bib2","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.it.2009.05.007","article-title":"The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology","volume":"30","author":"Vereecke","year":"2009","journal-title":"Trends Immunol."},{"key":"2026050409152300700_bib3","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1007\/s10875-024-01681-1","article-title":"The complexity of being A20: From biological functions to genetic associations","volume":"44","author":"Karri","year":"2024","journal-title":"J. Clin. Immunol."},{"key":"2026050409152300700_bib4","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1016\/j.jid.2023.12.007","article-title":"A20 haploinsufficiency: A systematic review of 177 cases","volume":"144","author":"Elhani","year":"2024","journal-title":"J. Invest. Dermatol."},{"key":"2026050409152300700_bib5","doi-asserted-by":"publisher","first-page":"574992","DOI":"10.3389\/fimmu.2020.574992","article-title":"Association of clinical phenotypes in haploinsufficiency A20 (HA20) with disrupted domains of A20","volume":"11","author":"Chen","year":"2020","journal-title":"Front. Immunol."},{"key":"2026050409152300700_bib73","first-page":"77","article-title":"Rare TNFAIP3 hypomorphic variants are a massively underestimated driver of human autoinflammatory disease","volume":"2666","author":"Lee","year":"2025","journal-title":"Arthritis Rheumatol. Abstr."},{"key":"2026050409152300700_bib7","doi-asserted-by":"publisher","first-page":"8217","DOI":"10.1074\/jbc.R800032200","article-title":"A20: Central gatekeeper in inflammation and immunity","volume":"284","author":"Coornaert","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2026050409152300700_bib8","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1126\/science.1182364","article-title":"Inhibition of NF-kappaB signaling by A20 through disruption of ubiquitin enzyme complexes","volume":"327","author":"Shembade","year":"2010","journal-title":"Science"},{"key":"2026050409152300700_bib9","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1038\/ncomms2567","article-title":"Regulation of A20 and other OTU deubiquitinases by reversible oxidation","volume":"4","author":"Kulathu","year":"2013","journal-title":"Nat. Commun."},{"key":"2026050409152300700_bib10","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/j.molcel.2010.10.009","article-title":"Ubiquitin binding to A20 ZnF4 is required for modulation of NF-\u03baB signaling","volume":"40","author":"Bosanac","year":"2010","journal-title":"Mol. Cell"},{"key":"2026050409152300700_bib11","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/s41590-020-0621-9","article-title":"Two distinct ubiquitin-binding motifs in A20 mediate its anti-inflammatory and cell-protective activities","volume":"21","author":"Martens","year":"2020","journal-title":"Nat. Immunol."},{"key":"2026050409152300700_bib12","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1038\/nri3313","article-title":"A20: Linking a complex regulator of ubiquitylation to immunity and human disease","volume":"12","author":"Ma","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"2026050409152300700_bib13","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/nature13322","article-title":"Negative regulation of the NLRP3 inflammasome by A20 protects against arthritis","volume":"512","author":"Vande Walle","year":"2014","journal-title":"Nature"},{"key":"2026050409152300700_bib14","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.immuni.2014.12.031","article-title":"A20 restricts ubiquitination of pro-interleukin-1\u03b2 protein complexes and suppresses NLRP3 inflammasome activity","volume":"42","author":"Duong","year":"2015","journal-title":"Immunity"},{"key":"2026050409152300700_bib15","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/s41556-019-0324-3","article-title":"A20 prevents inflammasome-dependent arthritis by inhibiting macrophage necroptosis through its ZnF7 ubiquitin-binding domain","volume":"21","author":"Polykratis","year":"2019","journal-title":"Nat. Cell Biol"},{"key":"2026050409152300700_bib16","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1136\/annrheumdis-2016-209454","article-title":"A20 inhibition of STAT1 expression in myeloid cells: A novel endogenous regulatory mechanism preventing development of enthesitis","volume":"76","author":"De Wilde","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"2026050409152300700_bib17","doi-asserted-by":"publisher","first-page":"30912","DOI":"10.1074\/jbc.M114.591966","article-title":"A20 regulates atherogenic interferon (IFN)-\u03b3 signaling in vascular cells by modulating basal IFN\u03b2 levels","volume":"289","author":"Moll","year":"2014","journal-title":"J. Biol. Chem."},{"key":"2026050409152300700_bib18","doi-asserted-by":"publisher","first-page":"2095","DOI":"10.1074\/jbc.M510326200","article-title":"Negative regulation of the retinoic acid-inducible gene I-induced antiviral state by the ubiquitin-editing protein A20","volume":"281","author":"Lin","year":"2006","journal-title":"J. Biol. Chem."},{"key":"2026050409152300700_bib19","doi-asserted-by":"publisher","first-page":"36592","DOI":"10.1074\/jbc.M111.283762","article-title":"ABIN1 protein cooperates with TAX1BP1 and A20 proteins to inhibit antiviral signaling","volume":"286","author":"Gao","year":"2011","journal-title":"J. Biol. Chem."},{"key":"2026050409152300700_bib20","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-213347","article-title":"A20 haploinsufficiency (HA20): Clinical phenotypes and disease course of patients with a newly recognised NF-kB-mediated autoinflammatory disease","volume":"78","author":"Berteau","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"2026050409152300700_bib21","doi-asserted-by":"publisher","first-page":"1548042","DOI":"10.3389\/fimmu.2025.1548042","article-title":"Clinical characteristics and treatment strategies for A20 haploinsufficiency in Japan: A national epidemiological survey","volume":"16","author":"Shiraki","year":"2025","journal-title":"Front. Immunol."},{"key":"2026050409152300700_bib22","doi-asserted-by":"publisher","first-page":"00083","DOI":"10.1016\/j.jaci.2026.02.002","article-title":"Multicenter international cohort study of haploinsufficiency of A20 reveals novel genetic architecture and phenotypic evolution","volume":"S0091\u20136749","author":"He","year":"2026","journal-title":"J. Allergy Clin. Immunol."},{"key":"2026050409152300700_bib49","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1186\/s13023-025-04004-8","article-title":"Clinical features and genetic analysis of A20 haploinsufficiency","volume":"20","author":"Xue","year":"2025","journal-title":"Orphanet J. Rare Dis."},{"key":"2026050409152300700_bib69","doi-asserted-by":"publisher","first-page":"1624715","DOI":"10.3389\/fped.2025.1624715","article-title":"Case report: Exploring the spectrum of A20 haploinsufficiency in children","volume":"13","author":"Jayaraman","year":"2025","journal-title":"Front. Pediatr."},{"key":"2026050409152300700_bib70","doi-asserted-by":"publisher","first-page":"520","DOI":"10.3899\/jrheum.2024-1134","article-title":"Isolated urticarial rash in the clinical spectrum of HA20","volume":"52","author":"Mastrolia","year":"2025","journal-title":"J. Rheumatol."},{"key":"2026050409152300700_bib71","doi-asserted-by":"publisher","first-page":"uxaf048","DOI":"10.1093\/cei\/uxaf048","article-title":"A novel missense variant in TNFAIP3 associated with autoimmunity reveals the contribution of STAT1\/mTOR pathways","volume":"219","author":"Potjewijd","year":"2025","journal-title":"Clin. Exp. Immunol."},{"key":"2026050409152300700_bib26","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1007\/s10875-020-00792-9","article-title":"Haploinsufficiency of A20 due to novel mutations in TNFAIP3","volume":"40","author":"He","year":"2020","journal-title":"J. Clin. Immunol."},{"key":"2026050409152300700_bib23","doi-asserted-by":"publisher","DOI":"10.70962\/jhi.20250003","article-title":"Human inborn errors of immunity: 2024 update on the classification from the international union of immunological societies expert committee","volume":"1","author":"Poli","year":"2025","journal-title":"J. Hum. Immun."},{"key":"2026050409152300700_bib24","volume-title":"GeneReviews","author":"Deuitch","year":"2024"},{"key":"2026050409152300700_bib25","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of medical genetics and genomics and the association for molecular pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"2026050409152300700_bib27","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s13075-021-02434-w","article-title":"Functional analysis of novel A20 variants in patients with atypical inflammatory diseases","volume":"23","author":"Kadowaki","year":"2021","journal-title":"Arthritis Res. Ther."},{"key":"2026050409152300700_bib28","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.81280","article-title":"A critical region of A20 unveiled by missense TNFAIP3 variations that lead to autoinflammation","volume":"12","author":"El Khouri","year":"2023","journal-title":"Elife"},{"key":"2026050409152300700_bib29","doi-asserted-by":"publisher","first-page":"955079","DOI":"10.3389\/fimmu.2022.955079","article-title":"Three Chinese pedigrees of A20 haploinsufficiency: Clinical, cytokine and molecular characterization","volume":"13","author":"Tian","year":"2022","journal-title":"Front. Immunol."},{"key":"2026050409152300700_bib30","doi-asserted-by":"publisher","first-page":"104453","DOI":"10.1016\/j.cellimm.2021.104453","article-title":"A novel missense mutation in TNFAIP3 causes haploinsufficiency of A20","volume":"371","author":"Jiang","year":"2022","journal-title":"Cell Immunol"},{"key":"2026050409152300700_bib31","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s13073-019-0690-2","article-title":"Recommendations for application of the functional evidence PS3\/BS3 criterion using the ACMG\/AMP sequence variant interpretation framework","volume":"12","author":"Brnich","year":"2029","journal-title":"Genome Med."},{"key":"2026050409152300700_bib32","article-title":"Schwartz, and I. Aksentijevich. Haploinsufficiency of A20. In GeneReviews [Internet]. M.P. Adam, S. Bick, G.M. Mirzaa, R.A. Pagon, S.E. Wallace, and A. Amemiya, editors. University of Washington, Seattle, WA","author":"Deuitch"},{"key":"2026050409152300700_bib33","doi-asserted-by":"publisher","first-page":"1628","DOI":"10.1002\/art.42486","article-title":"Reduction of neutrophil activation by phosphodiesterase 4 blockade in Beh\u00e7et\u2019s disease","volume":"75","author":"Le Joncour","year":"2023","journal-title":"Arthritis Rheumatol."},{"key":"2026050409152300700_bib34","doi-asserted-by":"publisher","first-page":"755","DOI":"10.4103\/idoj.idoj_779_24","article-title":"Effectiveness and safety of oral apremilast in the management of oral ulcers in Behcet\u2019s disease: A systematic review","volume":"16","author":"Mahajan","year":"2025","journal-title":"Indian Dermatol. Online J."},{"key":"2026050409152300700_bib35","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1111\/1346-8138.17972","article-title":"Roflumilast for oral ulcers in Beh\u00e7et\u2019s disease and recurrent aphthous stomatitis","volume":"52","author":"Chung","year":"2025","journal-title":"J. Dermatol."},{"key":"2026050409152300700_bib36","first-page":"616","article-title":"Colchicine-induced lactose malabsorption in patients with familial Mediterranean fever","volume":"31","author":"Fradkin","year":"1995","journal-title":"Isr. J. Med. Sci."},{"key":"2026050409152300700_bib37","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1136\/annrheumdis-2019-215918","article-title":"Type I interferon signature predicts response to JAK inhibition in haploinsufficiency of A20","volume":"79","author":"Schwartz","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"2026050409152300700_bib38","doi-asserted-by":"publisher","first-page":"823847","DOI":"10.3389\/fped.2022.823847","article-title":"Anakinra in paediatric Rheumatology and periodic fever clinics: Is the higher dose safe?","volume":"10","author":"Fingerhutov\u00e1","year":"2022","journal-title":"Front. Pediatr."},{"key":"2026050409152300700_bib39","doi-asserted-by":"publisher","first-page":"2375","DOI":"10.1002\/art.34409","article-title":"Sustained response and prevention of damage progression in patients with neonatal-onset multisystem inflammatory disease treated with anakinra: A cohort study to determine three- and five-year outcomes","volume":"64","author":"Sibley","year":"2012","journal-title":"Arthritis Rheum."},{"key":"2026050409152300700_bib40","doi-asserted-by":"publisher","first-page":"1454","DOI":"10.1001\/jamadermatol.2022.2124","article-title":"Anakinra-associated amyloidosis","volume":"158","author":"Alehashemi","year":"2022","journal-title":"JAMA Dermatol."},{"key":"2026050409152300700_bib41","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1002\/art.42664","article-title":"Anakinra-associated systemic amyloidosis","volume":"76","author":"Alehashemi","year":"2024","journal-title":"Arthritis Rheumatol."},{"key":"2026050409152300700_bib42","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1002\/art.40055","article-title":"Cerebrospinal fluid cytokines correlate with aseptic meningitis and blood-brain barrier function in neonatal-onset multisystem inflammatory disease: Central nervous system biomarkers in neonatal-onset multisystem inflammatory disease correlate with central nervous system inflammation","volume":"69","author":"Rodriguez-Smith","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"2026050409152300700_bib43","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1016\/j.immuni.2023.05.014","article-title":"Identification of an IL-1 receptor mutation driving autoinflammation directs IL-1-targeted drug design","volume":"56","author":"Wang","year":"2023","journal-title":"Immunity"},{"key":"2026050409152300700_bib44","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1002\/cpt.936","article-title":"Pharmacokinetics, pharmacodynamics, and proposed dosing of the oral JAK1 and JAK2 inhibitor baricitinib in pediatric and young adult CANDLE and SAVI patients","volume":"104","author":"Kim","year":"2018","journal-title":"Clin. Pharmacol. Ther."},{"key":"2026050409152300700_bib45","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1016\/j.jaip.2024.02.013","article-title":"Anifrolumab to treat a monogenic interferonopathy","volume":"12","author":"Doroudchi","year":"2024","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"2026050409152300700_bib46","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1007\/s10875-024-01826-2","article-title":"Normalized interferon signatures and clinical improvements by IFNAR1 blocking antibody (Anifrolumab) in patients with type I interferonopathies","volume":"45","author":"Kretzschmar","year":"2024","journal-title":"J. Clin. Immunol."},{"key":"2026050409152300700_bib47","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1002\/art.43145","article-title":"Sustained interferon signature suppression with Anifrolumab in a patient with STING-associated vasculopathy with onset in infancy refractory to JAK inhibitor and Dazukibart therapy","volume":"77","author":"Alehashemi","year":"2025","journal-title":"Arthritis Rheumatol."},{"key":"2026050409152300700_bib48","doi-asserted-by":"publisher","first-page":"2232","DOI":"10.1007\/s11606-019-05230-0","article-title":"Comparative effectiveness of combining MTX with biologic drug therapy versus either MTX or biologics alone for early rheumatoid arthritis in adults: A systematic review and network meta-analysis","volume":"34","author":"Donahue","year":"2019","journal-title":"J. Gen. Intern. Med."},{"key":"2026050409152300700_bib50","doi-asserted-by":"publisher","first-page":"104753","DOI":"10.1016\/j.cellimm.2023.104753","article-title":"Haploinsufficiency of A20 caused by a novel pathogenic missense variant of TNFAIP3 and successfully treated with anti-TNF and immunosuppressive therapies","volume":"391\u2013392","author":"Lina","year":"2023","journal-title":"Cell Immunol"},{"key":"2026050409152300700_bib51","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/S2468-1253(23)00008-0","article-title":"Combination biologic therapy for ulcerative colitis","volume":"8","author":"Vermeire","year":"2023","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"2026050409152300700_bib52","doi-asserted-by":"publisher","first-page":"jjaf161","DOI":"10.1093\/ecco-jcc\/jjaf161","article-title":"Combination therapy with biologics and\/or small molecules in inflammatory bowel disease: A comprehensive review","volume":"19","author":"Gisbert","year":"2025","journal-title":"J. Crohns Colitis"},{"key":"2026050409152300700_bib53","doi-asserted-by":"publisher","first-page":"103865","DOI":"10.1016\/j.autrev.2025.103865","article-title":"Combination targeted therapy with two biologic\/targeted synthetic DMARDs in 1200 patients with immune mediated inflammatory diseases. A systematic literature review for current landscape in safety and efficacy","volume":"24","author":"Lignou","year":"2025","journal-title":"Autoimmun. Rev."},{"key":"2026050409152300700_bib54","doi-asserted-by":"publisher","first-page":"151","DOI":"10.3390\/vaccines11010151","article-title":"Current evidence on vaccinations in pediatric and adult patients with systemic autoinflammatory diseases","volume":"11","author":"Massaro","year":"2023","journal-title":"Vaccines"},{"key":"2026050409152300700_bib55","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1136\/annrheumdis-2017-eular.3349","article-title":"THU0495 effectiveness of childhood vaccinations in caps patients treated with canakinumab: Results from an open-label phase 3 extension study","volume":"76","author":"Brogan","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"2026050409152300700_bib56","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1097\/CCM.0000000000001402","article-title":"Interleukin-1 receptor blockade is associated with reduced mortality in sepsis patients with features of macrophage activation syndrome: Reanalysis of a prior phase III trial","volume":"44","author":"Shakoory","year":"2016","journal-title":"Crit. Care Med."},{"key":"2026050409152300700_bib57","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.3899\/jrheum.181018","article-title":"Use of anakinra in hospitalized patients with crystal-associated arthritis","volume":"46","author":"Liew","year":"2019","journal-title":"J. Rheumatol."},{"key":"2026050409152300700_bib58","doi-asserted-by":"publisher","first-page":"101785","DOI":"10.1016\/j.eclinm.2022.101785","article-title":"Efficacy and safety of early soluble urokinase plasminogen receptor plasma-guided anakinra treatment of COVID-19 pneumonia: A subgroup analysis of the SAVE-MORE randomised trial","volume":"56","author":"Akinosoglou","year":"2023","journal-title":"EClinicalMedicine"},{"key":"2026050409152300700_bib59","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1002\/acr.24893","article-title":"American College of Rheumatology\/American association of hip and knee surgeons guideline for the perioperative management of antirheumatic medication in patients with rheumatic diseases undergoing elective total hip or total knee arthroplasty","volume":"74","author":"Goodman","year":"2022","journal-title":"Arthritis Care Res. (Hoboken)"},{"key":"2026050409152300700_bib72","doi-asserted-by":"publisher","first-page":"1508307","DOI":"10.3389\/fimmu.2024.1508307","article-title":"Case report: Adult case of A20 haploinsufficiency suspected as neuro-Beh\u00e7et disease","volume":"15","author":"Shirai","year":"2024","journal-title":"Front. Immunol."}],"container-title":["Journal of Human Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jhi\/article-pdf\/doi\/10.70962\/jhi.20250138\/2033007\/jhi_20250138.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jhi\/article-pdf\/doi\/10.70962\/jhi.20250138\/2033007\/jhi_20250138.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T13:15:28Z","timestamp":1777900528000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jhi\/article\/2\/4\/e20250138\/282066\/How-I-Treat-Haploinsufficiency-of-A20How-I-Treat"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,4]]},"references-count":63,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,7,6]]}},"URL":"https:\/\/doi.org\/10.70962\/jhi.20250138","relation":{},"ISSN":["3065-8993"],"issn-type":[{"value":"3065-8993","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,4]]},"article-number":"e20250138"}}