Exploratory study of MYD88 L265P, rare NLRP3 variants and clonal hematopoiesis prevalence in patients with Schnitzler's Syndrome.

OBJECTIVE:Assess the prevalence of the MYD88 L265P mutation and variants within NLRP3, also to evaluate the status of oligoclonal haematopoiesis in 30 patients with Schnitzler Syndrome (SchS). METHODS:30 patients with SchS were recruited from 3 clinical centres. 6 patients with known acquired cryopyrin associated periodic syndrome (aCAPS) were included as controls. Allele-Specific Oligonucleotide PCR (ASO-PCR) for detection of the MYD88 L265P variant, Next-Generation Sequencing (NGS) of NLRP3 and 28 genes associated with Myelodysplastic Syndrome (MDS) and Gene Scanning for X inactivation. RESULTS:Activating NLRP3 mutations were not present within 11 SchS patients, who have not been sequenced for this gene previously. The MYD88 L265P variant was present in 9/30 SchS patients and somatic mutations associated with Clonal Hematopoiesis (CH) were identified in 1/30 SchS and 1/6 aCAPS patients. Evidence of non-random X inactivation was detected in one female with SchS and one female aCAPS patient. CONCLUSION:A shared molecular mechanism accounting for the pathogenesis of inflammation in SchS remains elusive. CH is not associated with other somatic mutations found in SchS or aCAPS patients.