Title

Systematic Evaluation of Nine Monogenic Autoinflammatory Diseases Reveals Common and Disease-Specific Correlations With Allergy-Associated Features

Authors

Daniella Muallem Schwartz, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
Moses M. Kitakule, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
Brian LP Dizon, NIAMS, National Institutes of Health, Bethesda, Maryland
Cristhian Gutierrez-Huerta, NIAMS, National Institutes of Health, Bethesda
Sarah A. Blackstone, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
Aarohan M. Burma, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
Aran Son, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
Natalie Deuitch, National Human Genome Research Institute, Bethesda, Maryland
Sofia Rosenzweig, National Human Genome Research Institute, Bethesda, Maryland
Hirsh Komarow, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
Deborah L. Stone, National Human Genome Research Institute, Bethesda, Maryland
Anne Jones, National Human Genome Research Institute, Bethesda, Maryland
Michele Nehrebecky, National Human Genome Research Institute, Bethesda, Maryland
Patrycja Hoffmann, National Human Genome Research Institute, Bethesda, Maryland
Tina Romeo, National Human Genome Research Institute, Bethesda, Maryland
Adriana Almeida de Jesus, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
Sara Alehashemi, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
Megha Garg, Rochester Regional Health System
Sofia Torreggiani, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
Gina A. Montealegre Sanchez, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
Katelin Honer, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
Gema Souto Adeva, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
Karyl S. Barron, NIAID, National Institutes of Health, Bethesda, Maryland
Ivona Aksentijevich, National Human Genome Research Institute, Bethesda, Maryland
Amanda K. Ombrello, National Human Genome Research Institute, Bethesda, Maryland
Raphaela Goldbach-Mansky, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
Daniel L. Kastner, National Human Genome Research Institute, Bethesda, Maryland
Joshua D. Milner, Columbia University, New York, New York
Pamela Frischmeyer-Guerrerio, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland

Department

Rheumatology

Document Type

Article

Publication Title

Annals of the Rheumatic Diseases

Abstract

Background: Monogenic autoinflammatory diseases (AID) are caused by mutations in innate immune genes. The effects of these mutations on allergic inflammation are unknown.

Objectives: We investigated allergic, immunological and clinical phenotypes in FMF (familial Mediterranean fever), CAPS (cryopyrin-associated periodic syndrome), TRAPS (tumour necrosis factor receptor-associated periodic syndrome), HIDS (hyper-IgD syndrome), PAPA (pyogenic arthritis, pyoderma gangrenosum and acne), DADA2 (deficiency of adenosine deaminase 2), HA20 (haploinsufficiency of A20), CANDLE (chronic atypical neutrophilic dermatosis, lipodystrophy, elevated temperature) and SAVI (STING-associated vasculopathy of infancy).

Methods: In this cross-sectional study, clinical data were assessed in 425 patients with AID using questionnaires and chart reviews. Comparator data were obtained from public databases. Peripheral blood mononuclear cells obtained from 55 patients were stimulated and CD4+ cytokine production assessed.

Results: Clinical laboratory features of Type 2 immunity were elevated in CAPS but reduced in most AID, particularly DADA2. Physician-diagnosed allergic diseases were prevalent in multiple AID, including CAPS and DADA2. T helper 2 (Th2) cells were expanded in CAPS, TRAPS and HIDS; Th9 cells were expanded in HA20.

Conclusions: CAPS is characterised by an enhanced Type 2 signature, whereas FMF and CANDLE are associated with reduced Type 2 responses. DADA2 is associated with reduced Type 2 responses but a high rate of physician-diagnosed allergy. Therefore, NLRP3-driven autoinflammation may promote Type 2 immunity, whereas AID like DADA2 may manifest clinical phenotypes that masquerade as allergic disorders. Further investigations are needed to determine the contribution of autoinflammation to allergic clinical and immunological phenotypes, to improve the treatment of patients with AID.

DOI

10.1136/annrheumdis-2020-219137

Publication Date

2-22-2021

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