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 HealthFollow
• 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.

First Page

788

Last Page

795

DOI

10.1136/annrheumdis-2020-219137

Volume

80

Issue

6

Publication Date

6-2021

PubMed ID

33619160

Recommended Citation

Schwartz, D. M., Kitakule, M. M., Dizon, B. L., Gutierrez-Huerta, C., Blackstone, S. A., Burma, A. M., Son, A., Deuitch, N., Rosenzweig, S., Komarow, H., Stone, D. L., Jones, A., Nehrebecky, M., Hoffmann, P., Romeo, T., de Jesus, A. A., Alehashemi, S., Garg, M., Torreggiani, S., Montealegre Sanchez, G. A., Honer, K., Souto Adeva, G., Barron, K. S., Aksentijevich, I., Ombrello, A. K., Goldbach-Mansky, R., Kastner, D. L., Milner, J. D., & Frischmeyer-Guerrerio, P. (2021). Systematic Evaluation of Nine Monogenic Autoinflammatory Diseases Reveals Common and Disease-Specific Correlations With Allergy-Associated Features. Annals of the Rheumatic Diseases, 80 (6), 788-795. https://doi.org/10.1136/annrheumdis-2020-219137