Transcriptional heterogeneity of clonal plasma cells and immune evasion in immunoglobulin light chain amyloidosis

Immunoglobulin light chain amyloidosis (AL amyloidosis) is characterized by the presence of B cells producing amyloidogenic immunoglobulin light chains (LCs). The low frequency of aberrant B cells in AL is often masked by a polyclonal B cell background, making it difficult for treatment. We analyzed the single-cell RNA sequencing data from GEO database to compare the plasma cell (PCs) in four individuals with AL amyloidosis, one AL subject after treatment, and six healthy controls. High interindividual variability in AL-derived PCs in their expression pattern of known overexpressed genes in multiple myeloma and their usage of V regions in LCs was demonstrated. We also found overexpression of MHC class I molecules as one of the common features of clonal PCs in individuals with AL amyloidosis. Significantly reduced frequencies of circulating natural killer (NK) cells were also observed in a small cohort of AL patients when compared to healthy controls. These data demonstrate that aberrant PCs in AL has a highly diverse transcriptome, an upregulation of MHC, and a dampened capability of immunosurveillance by reduction of circulating NK frequencies. The analysis of clonal PCs at single cell level may provide a better approach for precise molecular profiling and diagnosis of AL amyloidosis.