Background:Cryopyrin-associated periodic syndromes (CAPS) are emerging autoinflammatory diseases with available treatment. No reports have yet been reported from Taiwan.Objectives:We reviewed cases suspected with CAPS to identify its existence in Taiwan.Methods:Genomic DNA from one hundred and ten cases with symptom signs suggestive of CAPS(1) between 2016-2019 were sent for NLRP3 gene analysis. Clinical presentations, laboratory data, treatment regimens, as well as inflammasome activities were analyzed among those treated in a tertiary medical center in northern Taiwan.Results:Among the 110 cases sequenced, 16 of them were found to carry missense mutations within the NLRP3 gene. Fourteen cases harbored known pathogenic genetic variants (c.1316C>T; c.1574A>T; and c.907G>C) and two carried novel NLRP3 missense mutations (c.210G>A, c.1371G>T)(2) with unknown pathophysiological roles. Through chart review, chronic urticarial, systemic juvenile idiopathic arthritis, Behcet’s disease and refractory Kawasaki disease were most likely diagnosed before genetic analysis were arranged. As compared to chronic infantile neurological, cutaneous and articular syndrome (CINCA) and Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS) was the most frequently observed clinical presentation. Plasma serumamyloidA (SAA) and IL-1b were both significantly elevated among the cases diagnosed with CAPS as compared to the controls (p<0.05). IL-18, on the other hand, showed no significant differences between the groups. While the presence of LPS without ATP significantly increased the level of IL-1b in the PBMC stimulation test, IL-18 were significantly elevated in the confirmed CAPS with or without ATP upon LPS stimulation (all p<0.05). Caspase 1 activity were also tested positive among the cases with CAPS. Furthermore, we compared the immune profiles between those CAPS cases harboring pathogenic mutations with the 2 harboring unreported NLRP3 missense mutations and discovered that the PBMC stimulation test in cases with c.210G>A and c.1371G>T mutation did not differ from the healthy controls.Conclusion:The number of NLRP3 gene alterations among patients suspected with CAPS in Taiwan is not low. In order to identify potential patients for proper medical intervention in the future, physician awareness, genetic testing as well as functional analysis are important.References:[1]Kuemmerle-Deschner JB, Ozen S, Tyrrell PN, Kone-Paut I, Goldbach-Mansky R, Lachmann H, et al. Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS). Ann Rheum Dis. 2017;76(6):942-7.[2]Van Gijn ME, Ceccherini I, Shinar Y, Carbo EC, Slofstra M, Arostegui JI, et al. New workflow for classification of genetic variants’ pathogenicity applied to hereditary recurrent fevers by the International Study Group for Systemic Autoinflammatory Diseases (INSAID). J Med Genet. 2018;55(8):530-7Disclosure of Interests:Chao-Yi Wu Speakers bureau: Abbvie, Boehringer Ingelheim International GmbH, Nestle, Pi-Shuang Chu: None declared, Huang-Yu Yang: None declared
Bridging autoinflammatory and autoimmune diseases