Human Soluble RANK ELISA Kit

Familial expansile osteolysis(1,2) (FEO, MIM 174810) is a rare, autosomal dominant bone disorder characterized by focal areas of increased bone remodelling. The osteolytic lesions, which develop usually in the long bones during early adulthood, show increased osteoblast and osteoclast activity. Our previous linkage studies mapped the gene responsible for FEO to an interval of less than 5 cM between D18564 and D18551 on chromosome 18q21.2-21.3 in a large Northern Irish family(3,4). The gene encoding receptor activator of nuclear factor-kappa B (RANK; ref. 5), TNFRSF11A, maps to this region. RANK is essential in osteoclast formation(6,7). We identified two heterozygous insertion mutations in exon 1 of TNFRSF11A in affected members of four families with FEO or familial Paget disease of bone (PDB). One was a duplication of 18 bases and the other a duplication of 27 bases, both of which affected the signal peptide region of the RANK molecule. Expression of recombinant forms of the mutant RANK proteins revealed perturbations in expression levels and lack of normal cleavage of the signal peptide. Both mutations caused an increase in RANK-mediated nuclear factor-kappa B (NF-kappa B) signalling in vitro, consistent with the presence of an activating mutation.

NSAIDs-induced urticaria and/or angioedema (NIUA) is the most frequent entity of hypersensitivity reactions to NSAIDs. The underlying cause is considered to be because of a nonspecific immunological mechanism in which mast cells are key players. We studied the association of nine single nucleotide polymorphisms in five genes involved in mast cell activation (SYK, LAT1, PLCG1, PLA2G4A, and TNFRSF11A) in 450 NIUA patients and 500 controls. We identified several statistically significant associations when stratifying patients by symptoms: PLA2G4A rs12746200 (urticaria vs. controls, P-c=0.005). PLCG1 rs2228246 (angioedema vs. controls; P-c=0.044), and TNFRS11A rs1805034 (urticaria+angioedema vs. controls; P-c=0.041). The frequency of haplotype PLCG1 rs753381-rs2228246 (C-G) in angioedema-NIUA patients was lower than that in controls (P-c=0.040). In addition, the haplotype frequency of TNFRS11A rs1805034-rs35211496 (C-T) was higher among urticaria-NIUA and urticaria+angioedema-NIUA patients than the controls (P-c=0.045 and 0.046). Our results shed light on the involvement of variants in genes related to non-immunological mast cell activation in NIUA. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.