# The Immunological Mechanisms Involved in the Pathophysiology of Allergic Proctocolitis

## TL;DR

This study explores the immune mechanisms behind allergic proctocolitis, finding that innate immune cells like NK cells and eosinophils may play a key role rather than T cells.

## Contribution

The study identifies innate immune markers (NK16+56- cells and eosinophils) as potential indicators of non-IgE-mediated cow’s milk allergy in infants.

## Key findings

- Infants with FPIAP had higher T-CD4 memory cells, regulatory B cells, and Tregs during the acute phase compared to healthy infants.
- Elevated levels of granulocytes, dendritic cells (mDC2), and NK16+56- cells were observed in FPIAP infants.
- NK16+56- cells and granulocytes were the best markers for distinguishing FPIAP from healthy infants based on ROC curves.

## Abstract

Background: The pathophysiology of non-IgE-mediated cow’s milk allergy is mostly unknown. Previous studies suggested a mechanism mediated by T cells, but this was not confirmed in subsequent studies. The aim of this study was to investigate the immunological mechanisms, especially the role of regulatory T cells (Tregs), in the pathophysiology of allergic proctocolitis (FPIAP). Methods: A prospective observational study was conducted on infants with FPIAP and a control group of healthy infants with similar ages. The main variables were lymphocyte populations, included Tregs, which were extracted from peripheral blood and processed immediately by flow cytometry at two time points: in the acute phase (“T0”) and after clinical resolution (“Tres”). Results: A total of 32 patients with FPIAP and 10 healthy infants were enrolled. There was a higher T-CD4 memory cell count, increased numbers of regulatory B cells and a higher percentage of Tregs (p < 0.01) in patients with acute FPIAP in contrast to the healthy group. The levels of granulocytes (mainly eosinophils), dendritic cells (mDC2) and NK16+56- cells were also significantly higher in the FPIAP group. NK16+56- cells and the number of granulocytes appeared to be the best markers for distinguishing between the healthy and FPIAP infants based on the ROC curves. Conclusions: FPIAP does not appear to have an immune mechanism mediated by T cells, but it may be associated with innate immunity responses characterized by an increase in NK16+56- cells, eosinophils and dendritic cells. These cells could be evaluated in future studies as possible markers of non-IgE-mediated cow’s milk protein allergy.