Discussion
We showed that solid FPIES reaction on OFC is accompanied by an elevation of TARC ratio. Our study included eight OFC (six cases) which pre-OFC TARC levels were over upper limit of age-appropriate value (data not shown). Two of six cases had eczema, however, the other four cases lacked eczema. These suggested that TARC ratio could be available regardless of baseline serum TARC levels.
TARC ratio correlated with post-OFC CRP levels. A recent study demonstrates that CRP levels increase in positive OFC suggesting inflammatory mechanisms in FPIES.4 FPIES is thought to be a T cell-mediated disorder, leading to local T cell infiltration with exaggerated expression of proinflammatory cytokines such as tumor necrosis factor-α and suppression of anti-inflammatory cytokine, transforming growth factor-β.5 An acute FPIES reaction is also associated with a skewing of the T cells cytokine profiles to Th2 response.6 On the other hand, regulatory T cells may play a role in the acquisition of tolerance.7 TARC promotes intestinal inflammation and counteracts regulatory T cell-mediated protection from colitis in mice.8Indeed, TARC expression is enhanced in the intestine of experimental allergic mice with diarrhea,9 although little is known about the pathological roles of TARC in T cell homing to the intestinal mucosa. These findings suggest that TARC is involved in the development of intestinal inflammation of solid FPIES. In contrast to OFC-positive patients, TARC levels showed no changes in any OFC-negative patients who finally achieved tolerances of solid FPIES. Thus, TARC ratio might be used to predict tolerance acquisition.
Our study is limited by retrospective review of small number of patients from a single institute. Additionally, elicited foods were limited to EY, wheat, scallop, and soy. Since not all OFC-positive patients showed elevation of serum TARC levels after OFC, further study is necessary to investigate correlations between TARC ratio and severity, doses of challenge, or causative foods.
In conclusion, TARC ratio may be a potentially useful biomarker to diagnose and manage solid FPIES irrespective of the presence of eczema. An understanding the pathological roles of TARC may provide new strategy for the management of solid FPIES.