Peripheral Blood Cell Gene Expression Diagnostic for Identifying Symptomatic Transthyretin Amyloidosis Patients: Male and Female Specific Signatures.

摘要: Background: Early diagnosis of familial transthyretin (TTR) amyloid diseases remains challenging because variable disease penetrance. Currently, patients must have an positive tissue biopsy to be eligible for disease-modifying therapies. Endomyocardial biopsies are typically when cardiomyopathy is suspected, but this manifestation generally diagnosed late. often difficult exhibit apparent symptoms polyneuropathy, a negative biopsy. Thus, there pressing need additional early diagnostic strategy TTR-aggregation-associated polyneuropathy and cardiomyopathy. Methods Findings: Global peripheral blood cell mRNA expression profiles from 263 tafamidis-treated untreated V30M Familiar Amyloid Neuropathy patients, asymptomatic carriers, healthy, age- sex-matched controls without TTR mutations were used differentiate symptomatic patients. We demonstrate that gene patterns reveal sex-independent, as well male- female-specific inflammatory signatures in FAP not carriers. These differentiated carriers with >80% accuracy. There was global downregulation the eIF2 pathway its associated genes all also demonstrated molecular scores based on these significantly trended toward normalized values independent cohort 46 after only 3 months tafamidis treatment. Conclusions: This study identifies novel affected males females. envision using approach, initially parallel biopsies, identify individuals who may convert Upon further validation, profiling could become diagnostic. quantitative signature biomarker significant effects drugs drug candidates. For example, new modifiers being evaluated clinical trial, such surrogate biomarkers potential provide objective, mechanistic response therapy.