Fig. 4: AA-4 clinical timeline and somatic mutations.
From: Somatic mutations in lymphocytes in patients with immune-mediated aplastic anemia
A Samples analyzed with scRNA + TCRab-seq from index patient AA-4 are marked on the clinical timeline. In addition, BM biopsies were taken at the time of influenza A infection and preceding severe AA diagnosis. Blood counts are plotted in upper four panels (B-Hb = hemoglobin (g/l), B-neut = neutrophils (E9/l), B-trom = thrombocytes (E9/l), E-retik = reticulocyte percentage of erythrocytes). Corticosteroid (prednisolone) and cyclosporine A (CyA) dosages (mg) are plotted in two panels below. Timing of ATG treatment and influenza A infection are marked with arrows. B Somatic STAT3 Y640F mutation was validated with amplicon sequencing of sorted Vbeta 5.1+ fraction, but the mutation was neither detected in Vbeta 14+ nor in Vbeta 5.1− fraction (in sample 2). Picture of BAM files opened at variant site (chr17:42322464) in Integrative Genomics Viewer. C Most expanded CTL clones of AA-4 at diagnosis (sample 1) and remission (sample 3), based on TCRb sequencing. On the x axis are different time points and y axis shows the frequency of each TCRb clone from whole CTL TCRb repertoire. At diagnosis, there were two ~20% CTL clones, which significantly diminished during immunosuppressive treatment. Vbeta 5.1 and Vbeta 14 correspond to expanded T-cell clones TCRBV05-01 and TCRBV19-01, respectively.
