F. Eroglu1, O. Kasapcopur2, N. Beşbaş3, F. Ozaltin4, Y. Bilginer5, K. Barut6, A. Mensa-Vilaro7, K. Nakagawa8, T. Heike9, R. Nishikomori10, J. Arostegui11, S. Ozen12
2016 Vol.34, N°6 ,Suppl.102 - PI 0115, PF 0120
The aim of this study was to present the genetic and clinical data of the largest cohort of Turkish cryopyrin-associated periodic syndromes (CAPS) patients.
This is a two-centre descriptive study of Turkish children with clinical diagnosis of CAPS. NLRP3 analyses were performed by Sanger sequencing and by massively parallel sequencing. ASC dependent NF-κB activation and transfection-induced THP-1 cell death assays determined the functional consequences of the detected variants. Disease activity and response to anti interleukin 1 (anti-IL-1) treatment was also assessed.
Heterozygous germline NLRP3 mutation was detected in 8 of 14 enrolled patients (57.1%). Two novel somatic mutations Y560H and G307D were found which induced both THP-1 cell death and ASC dependent NF-kB activation. With anti-IL-1 treatment the disease activity was improved in all patients except one. Except two patients with macrophage activation syndrome (MAS) attack, there were no serious adverse events requiring hospitalisation.
CAPS should be considered in all patients with typical symptoms even if Sanger-based genetic analysis is negative, since a considerable number of patients have mosaicism. Treatment should be patient-tailored and MAS should be considered as a rare complication.
PMID: 27191192 [PubMed]
Received: 10/08/2015 - Accepted : 05/01/2016 - In Press: 10/05/2016 - Published: 25/10/2016