Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1β, IL-12/VEGF, and IL-10/IP-10 Axis

Figure 6

Signatures of cell phenotype features and serum immunological biomarkers in patients with sickle cell anemia according to laboratorial and clinical records. The signatures of cell phenotype features (a, b) and serum immunological biomarkers (c, d) were assembled considering the frequency of subjects with values above the global median cut-off determined for each biomarker. The SCA patients were categorized according to their laboratorial and clinical records, including reticulocyte counts, platelet levels, and death risk scores. The global median values for each biomarker were used as the cut-off to classify each subject with “low” or “high” biomarker levels. Overlay of ascendant biomarker signature curves was employed to identify those biomarkers with frequency of subjects above the 50th percentile (dashed lines) further highlighted by gray background. Venn diagram analyses were carried out to identify those biomarkers commonly or selectively observed among groups. The universal biomarkers observed in all SCA subgroups were tagged by black squares. Those biomarkers with putative association with SCA subgroups were tagged with a gray diamond for SCA patients with low reticulocyte counts, a dark gray circle for SCA patients with high platelet counts, or a dark gray triangle for SCA patients with high death risk.