Anti-TNFRSF11B monoclonal antibody, clone 6B22

Juvenile Paget disease (JPD) {MIM 239000} is a rare inherited bone disease that affects children. The patients affected with JPD present an altered bone turnover, therefore, show a phenotype characterized by progressive bone deformities, fractures, and short stature. Deletions or missense mutations of the TNFRSN11B gene are common in these children. This gene encodes a soluble protein, the osteoprotegerin, which leads to uncontrolled osteoclastogenesis when mutated. JPD is characterized by a strong genotype-phenotype correlation, so depending on the alteration of the TNFRSN11B gene, the phenotype is variable. This review describes the different clinical features which are characteristic of JPD and the correspondence with the different molecular alterations of the TNFRSN11B gene.

Osteoprotegerin is involved in the progression of atherosclerosis. This study aimed to determine whether TNFRSF11B polymorphisms are associated with prognosis of large artery atherosclerosis (LAA) stroke. Three TNFRSF11B polymorphisms (rs2073617, rs2073618 and rs3134069) were genotyped in 1010 patients with LAA stroke. Short-term outcome was evaluated using the modified Rankin Scale score at 3-month after stroke onset. Long-term outcome was assessed using the stroke recurrence. We found that rs2073617G was associated with an increased risk of poor outcome of LAA stroke (additive model: odds ratio (OR) = 1.35, 95% confidence interval (CI) = 1.06-1.73). This association was also observed in rs3134069C (additive model: OR = 1.53, 95% CI = 1.10-2.12). Furthermore, when we combined these two polymorphisms according to the numbers of risk alleles (rs2073617G and rs3134069C), we found that the patients with 3-4 risk alleles were statistically significantly associated with an increased risk of poor outcome of LAA stroke (OR = 1.90, 95% CI = 1.10-3.28) compared with 0-2 risk alleles, and this increased risk was more evident among those with hypertension (OR = 2.02, 95% CI = 1.04-3.91), those without diabetes (OR = 2.02, 95% CI = 1.02-4.01) and those with smoking (OR = 2.43, 95% CI = 1.09-5.42). In silico analysis showed that rs2073617 and rs3134069 are located in various histone modification marked regions, DNase I hypersensitive sites and can change the binding of regulatory motifs. Moreover, rs2073617 is also located in the binding site of transcription factors. Our findings suggested that TNFRSF11B polymorphisms may be associated with an increased risk of short-term poor outcome of LAA stroke.