B cell exhaustion in sickle cell disease patients is associated with inhibited memory generation after influenza vaccination (P3009)

• Published in: The Journal of immunology (1950) 2013-05, Vol.190 (1_Supplement), p.55-55.5
• Main Authors: Szczepanek, Steven, Adami, Alex, Louis, Deirdre, Farrington, Narye, Bracken, Sonali, Natarajan, Prabitha, Secor, Eric, Jellison, Evan, Thrall, Roger, Andemariam, Biree
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.190.Supp.55.5

Dysregulated immunity is a hallmark of Sickle Cell Disease (SCD), and clinical evidence indicates that SCD patients mount adequate initial antigen-specific antibody responses only to have significant drops in titer levels 1-2 years post-vaccination. We thus hypothesized that SCD patients do not generate sufficient B-cell memory after vaccination. We conducted a translational study (IRB #11-026-1) using flow cytometric analysis of memory B-cells from frozen PBMCs taken from 11 SCD patients and 9 healthy controls before and 4-6 weeks after receiving the influenza vaccine. Percentages of CD19+ B-cells were similar between groups before vaccination, but only SCD patients showed a significant increase in B-cells after vaccination (P=0.04). However, control subjects generated approximately 2-fold more CD27+ memory B-cells after vaccination (P=0.03) while almost no change was observed in the SCD patients. This indicates that SCD patients generate naïve, but little to no memory B-cells after vaccination, thereby explaining the diminishing antibody titers observed by clinicians. Further analysis demonstrated that SCD patients have a significantly higher proportion of FcRL4+ exhausted B-cells at baseline when compared to controls (33% more; P=0.02). Given that FcRL4 down-regulates BCR signaling and is associated with reduced memory B-cell generation in people with chronic infections, we propose that chronic inflammation in SCD leads to B-cell exhaustion through BCR signal dampening.