TY - JOUR T1 - Systematic evaluation of nine monogenic autoinflammatory diseases reveals common and disease-specific correlations with allergy-associated features JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 788 LP - 795 DO - 10.1136/annrheumdis-2020-219137 VL - 80 IS - 6 AU - Daniella Muallem Schwartz AU - Moses M Kitakule AU - Brian LP Dizon AU - Cristhian Gutierrez-Huerta AU - Sarah A Blackstone AU - Aarohan M Burma AU - Aran Son AU - Natalie Deuitch AU - Sofia Rosenzweig AU - Hirsh Komarow AU - Deborah L Stone AU - Anne Jones AU - Michele Nehrebecky AU - Patrycja Hoffmann AU - Tina Romeo AU - Adriana Almeida de Jesus AU - Sara Alehashemi AU - Megha Garg AU - Sofia Torreggiani AU - Gina A Montealegre Sanchez AU - Katelin Honer AU - Gema Souto Adeva AU - Karyl S Barron AU - Ivona Aksentijevich AU - Amanda K Ombrello AU - Raphaela Goldbach-Mansky AU - Daniel L Kastner AU - Joshua D Milner AU - Pamela Frischmeyer-Guerrerio Y1 - 2021/06/01 UR - http://ard.bmj.com/content/80/6/788.abstract N2 - 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.Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. De-identified participant data (clinical diagnoses and laboratories) and flow cut-metric data are either included in the manuscript or available upon request to the corresponding author, Daniella Schwatz; Daniella.Schwartz@nih.gov. ER -