Molecular Expression Differences in Specific Blood Mononuclear Cell-Types Identify Patients With AL Amyloidosis

The diagnosis of AL amyloidosis is often challenging due to its systemic nature and heterogeneous clinical presentation. Current serological biomarkers for diagnosis and monitoring are not optimal. We have considered the possibility that mononuclear cell-type specific molecular expression can be used to develop blood-based biomarkers to diagnose and monitor patients with AL amyloidosis. Peripheral blood monocytes and CD4⁺ T cells from patients with documented AL amyloidosis or myeloma without amyloidosis were assessed by enhanced flow cytometric analysis for expression levels of 20 analytes chosen for the possibility that their expression levels may lead to diagnostic assays and biomarkers. We found definitive expression level differences for brain-derived neurotrophin factor (BDNF), calmodulin, and phospho-TBK1 in CD4⁺ T cells and for phospho-GSK3β in monocytes. Logistic regression and ROC analysis showed that BDNF in CD4⁺ T cells and heme oxygenase 1 in monocytes significantly distinguished between patients with myeloma versus patients with AL amyloidosis (AUC = 0.75). Additionally, we discovered remarkable differences in intermolecular associations between the samples from the two patient groups, suggesting the involvement of specific pathogenetic pathways. Our results demonstrate that mononuclear cell-type specific molecular expression may be useful for developing a diagnostic assay and biomarkers for patients with AL amyloidosis.