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. 2025 May 27;12(6):688.
doi: 10.3390/children12060688.

The Immunological Mechanisms Involved in the Pathophysiology of Allergic Proctocolitis

Jimena Pérez-Moreno  1 , Esther Bernaldo-de-Quirós  2 , Mar Tolín Hernani  1 , Guillermo Álvarez-Calatayud  1 , Laura Perezábad  2 , César Sánchez Sánchez  1 , Rafael Correa-Rocha  1
Affiliations

The Immunological Mechanisms Involved in the Pathophysiology of Allergic Proctocolitis

Jimena Pérez-Moreno et al. Children (Basel). .

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.

Keywords: FPIAP; cow’s milk protein allergy; food allergy; non-IgE-mediated cow’s milk allergy; regulatory T cells.

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Conflict of interest statement

There are no conflict of interests related to the manuscript content. All the authors declare that they have no competing financial interests.

Figures

Figure 1
Figure 1
Treg(Foxp3)/TCD4+TemRA ratios in both study groups (PROCT (T0/FPIAP) and control groups). Foxp3 is a marker of Treg cells. TemRA: effector T cells; PROCT: FPIAP group. *: statistically significant.
Figure 2
Figure 2
Comparison of percentage of activated basophils in FPIAP and control groups. *: statistically significant; ns: not statistically significant; Basof activ: activated basophils; Basof IgE+: IgE+ basophils.
Figure 3
Figure 3
Comparison of percentage of cytokine-secreting CD4+ T cells in FPIAP T0, FPIAP Tres and control groups. *: statistically significant.
Figure 4
Figure 4
Model of physiopathological immune response and Treg cells in FPIAP based on the results of this study. Purple circle are cytokines. Red graphic is to explain that TH1 and TH2 immune response are not activated. Checkmark symbol is to highlight T Reg cells are normal in number and function in the physiopathology immune response of FPIAP.
See this image and copyright information in PMC

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