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C5a Replaces IL-4 in Anti-CD40 + IL-4 Mediated Induction of IgE Responses By PBMC of Adult Allergic Asthmatic Humans
Sunday, March 6, 2016
South Exhibit Hall H (Convention Center)
Kobkul Chotikanatis, MD, Jane Yee, M.D., Yan Yan, MD, Seto M Chice, MS, Helen G. Durkin, PhD, Rauno Joks, M.D., Tamar A. Smith-Norowitz, PhD
Rationale:

Complement split products C5a and C3a levels increase in airways after allergen provocation in asthmatic humans We reported plasma C5a levels relate to asthma severity and QOL scores and that C5a and its receptor (CD88) are increased in blood of adult asthmatic humans requiring acute care in emergency rooms. We now investigate if C5a and C3a can induce IgE responses by PBMC stimulated with anti-CD40 in the absence of IL-4.

Methods:

PBMCs (1.5x106/mL) of allergic asthmatic humans  (n=4) (males or females, ages 36-59) were cultured for 2-10 days ± anti-CD40, ± IL-4  recombinant human C5a (0.1 to 10 μg/mL) or recombinant human C3a (10-4 to 10-2μg/mL), and the levels of IgE in culture supernatants determined (ELISA). 

Results:

We found that high levels of IgE were induced on day 10 when culture with anti-CD4- and IL-4 (25.0±17 ng/ml). In contrast, when anti-CD40 Ab or IL-4 alone were added, no IgE responses were induced.  We also found that when C5a, but not C3a, was substituted for IL-4, and PBMC culture with anti-CD40, similar high levels of IgE were induced (31.3±.2.8 ng/ml).

Conclusions:

C5a plays an important role in induction of human IgE responses.