Regulatory B Cell Levels and Their Association with Asthma Control in Children and Adolescents with Persistent Asthma
Adora Lin (Washington, United States of America), Shivani Chinnappan (Washington, United States of America), Dinesh Pillai (Washington, United States of America), Deepa Rastogi (Washington, United States of America), Sarah Hudock (Washington, United States of America), Stephen Teach (Washington, United States of America), Hemant Sharma (Washington, United States of America), Catherine Bollard (Washington, United States of America), William Sheehan (Washington, United States of America)
Background

Regulatory B cells (B regs) produce the immunomodulatory agent IL-10 which functions to suppress allergic inflammation and inhibit atopic disease.  Adults with allergic asthma have decreased frequencies of B regs compared to healthy controls; however, similar studies are lacking in pediatric asthma, where the allergic phenotype is dominant.  This pilot study sought to investigate (a) the frequency of B regs in children and adolescents with persistent asthma as compared to healthy controls and (b) the association between B reg frequency and asthma severity.    

Method

Blood samples were obtained from children and adolescents with persistent asthma (n=7).  Comparative analyses were done on blood samples from non-allergic, non-asthmatic healthy pediatric control patients (n=8).  Peripheral blood mononuclear cells were isolated and evaluated by flow cytometry to determine the frequency of B regs (IL-10+ B cells).  Furthermore, we evaluated the percentage of B cells expressing IL-10 receptor (IL-10R).  Finally, we analyzed if there was a correlation between the percentage of B regs and current asthma severity as defined by the Composite Asthma Severity Index (CASI).    

Results

The cohort (n=7) of pediatric patients with persistent asthma was 7-14 years old (median age of 12 years), 71% male, and 71% Black.  There was a decreased percentage of IL-10+ B regs among CD73- CD25+ CD71+ B cells in the persistent asthma group as compared to the healthy control group (median = 0.3% vs. 1.3%, p<0.01).  A similar trend was seen for a reduced percentage IL-10+ B regs among CD38+ CD27+ B Cells (2.2% vs. 3.9%, p=0.09).  IL-10R expression was decreased on memory B cells (p<0.01) and plasmablasts (p<0.01) in the children with persistent asthma as compared to controls.  Within the asthma group, there was a trend for the frequency of IL-10+ B regs being negatively correlated with asthma severity as defined by the CASI score (r = -0.67).           

Conclusion

In our pilot study, children and adolescents with persistent asthma had lower levels of B regs in peripheral blood as compared to healthy control children, and lower B reg frequencies may be associated with increased asthma severity.  Larger studies are warranted to further investigate the importance of B regs in pediatric asthma.