Asymmetrical 5'RACE RNA-based immunoglobulins repertoire sequencing is an accurate and specific tool for diagnosis of POEMS syndrome.

POEMS syndrome is a rare form of plasma cell dyscrasia with multiple clinical features including polyneuropathy and sclerotic bone lesions. As various signs and symptoms can be observed, diagnosis is often delayed and we need an accurate diagnosis tool for these patients. Vascular endothelial growth factor (VEGF) is known to play a major role in the pathology and is frequently increased in sera of the patients but is not specific. This condition is also associated with the presence of a monoclonal immunoglobulin light chain composed of highly restricted variable domains (IGLV1-40, IGLV1-44, IGLV1-36 and IGJV3*02 genes). Using RNA-based high-throughput sequencing (5 RACE RepSeq), we previously showed mutated consensus stretches in the CDR1/FR2 regions of the variable domains of the light chains: (P/A)VNWYQ and (D/G)VNWYQ. We have now added 70 light chain sequences to our cohort and confirmed the variable domain restriction, the consensus stretches and found a new YSVNWYQ pattern on IGLV1-44 light chains. When correlated with our clinical database of POEMS patients, these mutation patterns had an accuracy of 89% and a specificity of 100%. 5RACE RepSeq is an important tool to ensure the diagnosis of patients suspected of having POEMS syndrome, even with a small secretory clone. Samples from an involved organ are mandatory in the case of localized disease.