In:
Annals of the Rheumatic Diseases, BMJ, Vol. 80, No. 6 ( 2021-06), p. 788-795
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0003-4967
,
1468-2060
DOI:
10.1136/annrheumdis-2020-219137
Language:
English
Publisher:
BMJ
Publication Date:
2021
detail.hit.zdb_id:
1481557-6