Early Peanut OIT-Induced Suppression of Basophil Reactivity Is a Marker of Sustained Unresponsiveness
Sunday, March 6, 2016
South Exhibit Hall H (Convention Center)
Sarita U. Patil, MD, Johanna Steinbrecher, B.S., Alex Ma, B.S., Neal Smith, B.S., Cecilia Washburn, B.S., Alanna Hickey, Caroline Southwick, Lauren Tracy, Bert Ruiter, PhD, Yamini Virkud, MD, MA, MPH, Michael Schneider, Wayne Shreffler, MD PhD FAAAAI
Rationale: Peanut allergic subjects undergoing oral immunotherapy may or may not achieve a sustained clinical benefit. Biomarkers to identify those at risk for regaining allergic reactivity after active treatment are needed.

Methods:  Twenty-three peanut allergic children, aged 7-13 underwent PNOIT in a single-center, open-label trial. In those with challenge-proven desensitization after a 14-20 month-long protocol (n=22), sustained unresponsiveness was confirmed by DBPCFC after one month of peanut avoidance in 9 patients. Peripheral blood from multiple time points was stimulated in vitro (Arah1, Arah2, Arah6, whole peanut extract, anti-FcεRI) and basophil activation, based on upregulation of CD63, was assessed by flow cytometry. A data-driven analysis pipeline utilizing R/Bioconductor was created to derive summary statistics and analyses.

Results: Basophil reactivity is suppressed by one month into desensitization (CD63 logAUC: Arah2 298.1 vs 28.8 p<0.001, whole peanut 432.1 vs 26.9 p<0.001) among all patients and partially rebounds after 1 month of post treatment avoidance (Arah2 138.2, whole peanut 208.6). Although basophil reactivity was similar at baseline between patients who achieved sustained unresponsiveness (SU) versus those with transient desensitization (TD) (Arah2 p=0.5, whole peanut p=0.6), it was more significantly suppressed in SU patients by 1 month of PNOIT treatment (Arah2 p<0.001, whole peanut p<0.001) and that difference persisted through the desensitization phase (p<0.05). Furthermore, the post avoidance rebound of basophil reactivity was significantly less for SU patients to both Arah2 (p=0.03) and peanut (p=0.02) stimulation.

Conclusions: Basophil suppression one month after initiation of peanut immunotherapy may be an early biomarker for sustained unresponsiveness.