Publication:
Outcomes and Treatment Strategies for Autoimmunity and Hyperinflammation in Patients with RAG Deficiency

Simple item page
dc.contributor.authorÖZEN, AHMET OĞUZHAN
dc.contributor.authorsFarmer, Jocelyn R.; Foldvari, Zsofia; Ujhazi, Boglarka; De Ravin, Suk See; Chen, Karin; Bleesing, Jack J. H.; Schuetz, Catharina; Al-Herz, Waleed; Abraham, Roshini S.; Joshi, Avni Y.; Costa-Carvalho, Beatriz T.; Buchbinder, David; Booth, Claire; Reiff, Andreas; Ferguson, Polly J.; Aghamohammadi, Asghar; Abolhassani, Hassan; Puck, Jennifer M.; Adeli, Mehdi; Cancrini, Caterina; Palma, Paolo; Bertaina, Alice; Locatelli, Franco; Di Matteo, Gigliola; Geha, Raif S.; Kanariou, Maria G.; Lycopoulou, Lilia; Tzanoudaki, Marianna; Sleasman, John W.; Parikh, Suhag; Pinero, Gloria; Fischer, Bernard M.; Dbaibo, Ghassan; Unal, Ekrem; Patiroglu, Turkan; Karakukcu, Musa; Al-Saad, Khulood Khalifa; Dilley, Meredith A.; Pai, Sung-Yun; Dutmer, Cullen M.; Gelfand, Erwin W.; Geier, Christoph B.; Eibl, Martha M.; Wolf, Hermann M.; Henderson, Lauren A.; Hazen, Melissa M.; Bonfim, Carmem; Wolska-Kusnierz, Beata; Butte, Manish J.; Hernandez, Joseph D.; Nicholas, Sarah K.; Stepensky, Polina; Chandrakasan, Shanmuganathan; Miano, Maurizio; Westermann-Clark, Emma; Goda, Vera; Krivan, Gergely; Holland, Steven M.; Fadugba, Olajumoke; Henrickson, Sarah E.; Ozen, Ahmet; Karakoc-Aydiner, Elif; Baris, Safa; Kiykim, Ayca; Bredius, Robbert; Hoeger, Birgit; Boztug, Kaan; Pashchenko, Olga; Neven, Benedicte; Moshous, Despina; de Villartay, Jean-Pierre; Bousfiha, Ahmed Aziz; Hill, Harry R.; Notarangelo, Luigi D.; Walter, Jolan E.
dc.date.accessioned2022-03-14T10:21:26Z
dc.date.available2022-03-14T10:21:26Z
dc.date.issued2019-07
dc.description.abstractBACKGROUND: Although autoimmunity and hyperinflammation secondary to recombination activating gene (RAG) deficiency have been associated with delayed diagnosis and even death, our current understanding is limited primarily to small case series. OBJECTIVE: Understand the frequency, severity, and treatment responsiveness of autoimmunity and hyperinflammation in RAG deficiency. METHODS: In reviewing the literature and our own database, we identified 85 patients with RAG deficiency, reported between 2001 and 2016, and compiled the largest case series to date of 63 patients with prominent autoimmune and/or hyperinflammatory pathology. RESULTS: Diagnosis of RAG deficiency was delayed a median of 5 years from the first clinical signs of immune dysregulation. Most patients (55.6%) presented with more than 1 autoimmune or hyperinflammatory complication, with the most common etiologies being cytopenias (84.1%), granulomas (23.8%), and inflammatory skin disorders (19.0%). Infections, including live viral vaccinations, closely preceded the onset of autoimmunity in 28.6% of cases. Autoimmune cytopenias had early onset (median, 1.9, 2.1, and 2.6 years for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, respectively) and were refractory to intravenous immunoglobulin, steroids, and rituximab in most cases (64.7%, 73.7%, and 71.4% for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, respectively). Evans syndrome specifically was associated with lack of response to first-line therapy. Treatment-refractory autoimmunity/ hyperinflammation prompted hematopoietic stem cell transplantation in 20 patients. CONCLUSIONS: Autoimmunity/hyperinflammation can be a presenting sign of RAG deficiency and should prompt further evaluation. Multilineage cytopenias are often refractory to immunosuppressive treatment and may require hematopoietic cell transplantation for definitive management. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.
dc.identifier.doi10.1016/j.jaip.2019.02.038
dc.identifier.eissn2213-2201
dc.identifier.issn2213-2198
dc.identifier.pubmed30877075
dc.identifier.urihttps://hdl.handle.net/11424/244384
dc.identifier.wosWOS:000473777600035
dc.language.isoeng
dc.publisherELSEVIER SCIENCE BV
dc.relation.ispartofJOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectRecombination activating gene (RAG)
dc.subjectSevere combined immunodeficiency (SCID)
dc.subjectImmune dysregulation
dc.subjectAutoimmune cytopenias
dc.subjectHematopoietic stem cell transplantation (HSCT)
dc.subjectSEVERE COMBINED IMMUNODEFICIENCY
dc.subjectRECOMBINATION ACTIVITY
dc.subjectGRANULOMATOUS-DISEASE
dc.subjectCLINICAL PHENOTYPES
dc.subjectVACCINE-STRAIN
dc.subjectOMENN SYNDROME
dc.subjectMUTATIONS
dc.subjectCYTOPENIAS
dc.subjectRITUXIMAB
dc.subjectGENE
dc.titleOutcomes and Treatment Strategies for Autoimmunity and Hyperinflammation in Patients with RAG Deficiency
dc.typearticle
dspace.entity.typePublication
local.avesis.idd4afc08c-6793-4312-96f6-872e4358299e
local.import.packageSS16
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.numberofpages20
local.journal.quartileQ1
oaire.citation.endPage+
oaire.citation.issue6
oaire.citation.startPage1970
oaire.citation.titleJOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
oaire.citation.volume7
relation.isAuthorOfPublication3e9c297b-e636-4836-8f61-dc9c8b7c29cf
relation.isAuthorOfPublication.latestForDiscovery3e9c297b-e636-4836-8f61-dc9c8b7c29cf

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Farmer et al. - 2019 - Outcomes and Treatment Strategies for Autoimmunity.pdf
Size:
2.51 MB
Format:
Adobe Portable Document Format
Download

Collections

Research Outputs