Markers of gut mucosal inflammation and cow's milk specific immunoglobulins in non‐IgE cow's milk allergy

Abstract

BackgroundAllergy to cow’s milk protein (CMP) may cause gastrointestinal (GI) symptoms in the absence of CMP specific IgE. The immunological mechanisms involved in such disease are not fully understood. Therefore we examined markers of gut mucosal inflammation and the immunoglobulin profiles in children with Gl symptoms suspected of cow’s milk protein allergy (CMPA).Patients and methodsWe prospectively recruited infants and young children (n = 57; median age 8.7 months) with gastrointestinal complaints suspected of CMPA. The diagnosis of CMPA was made using the double-blind, placebo-controlled food challenge. Serum and stool samples were collected during CMP-free diet and after both placebo and active challenges. We analyzed the stool samples for calprotectin, human β-defensin 2 and IgA. In serum, we analyzed the levels of β-lactoglobulin and α-casein specific IgA, and IgG antibodies (total IgG and subclasses IgG1 and IgG4). Control group included children with e.g. dermatological or pulmonary problems, consuming normal diets.ResultsFecal calprotectin levels were higher in the challenge positive group (n = 18) than in the negative (n = 37), with respective geometric means 55 μg/g [95% confidence interval 38–81] and 29 [24–36] μg/g (p = 0.0039), during cow’s milk free diet. There were no significant inter-group differences in the fecal β-defensin and IgA levels. The CMP specific IgG and IgA were not elevated in patients with CMPA, but the levels of β-lactoglobulin-IgG4 (p = 0.0118) and α-casein-IgG4 (p = 0.0044), and total α-casein-IgG (p = 0.0054) and -IgA (p = 0.0050) in all patient samples (regardless of CMPA diagnosis) were significantly lower compared to the control group using dairy products.ConclusionsDespite cow’s milk elimination in children intolerant to cow’s milk there might be ongoing low-grade inflammation in the gut mucosa. CMP specific IgG or IgA should not be used to diagnose non-IgE CMPA. The observed frequency of impaired CMP specific total IgA, IgG and IgG4 production in patients following cow’s milk free diet warrants further studies.

The gut microbiota and inflammatory noncommunicable diseases: Associations and potentials for gut microbiota therapies

“…Increased gut permeability and intestinal inflammation with impaired immune-regulatory mechanisms have been shown in children with allergic disease 55 , and also in children with type 1 diabetes 56 . Consistent with reports of dysbiosis in children with allergic manifestations, an aberrant gut microbiome has been associated with type 1 diabetes 57,58 .…”

Elevated fecal calprotectin levels are associated with severity of atopic dermatitis in children

“…[10][11][12] Fecal calprotectin is a potentially important clinical test as a marker of gastrointestinal tract inflammation and has been increasingly used as a non-invasive marker for the diagnosis of bowel inflammation or gastrointestinal allergic diseases. 10,11,13 Although many studies have reported the relationship between fecal calprotectin and gastrointestinal inflammation or allergic diseases, calprotectin has rarely been studied in AD. The aims of this study were to examine fecal calprotectin levels in children with AD and to investigate its relationship with the severity of AD.…”

“…4 Numerous investigators have shown that changes in the gut microbiota and intestinal inflammation have been associated with the development of allergic diseases. 6,8,13,23 The gut microbiota controls intestinal inflammation, which further modulates the development of the systemic immune system. 8,23 Altered gut microbiota induces epithelial damage resulting in increased intestinal inflammation, altered gut permeability and immunological balance, which affect the development of allergic diseases.…”

“…8,23 Altered gut microbiota induces epithelial damage resulting in increased intestinal inflammation, altered gut permeability and immunological balance, which affect the development of allergic diseases. 8,13,23 The damaged epithelium with increased permeability might allow for the passage of allergens. 24 Prolonged enhanced permeability and increased exposure to allergens might result in the subsequent development of atopic eczema.…”

The gut microbiota and inflammatory noncommunicable diseases: Associations and potentials for gut microbiota therapies

“…Increased gut permeability and intestinal inflammation with impaired immune-regulatory mechanisms have been shown in children with allergic disease 55 , and also in children with type 1 diabetes 56 . Consistent with reports of dysbiosis in children with allergic manifestations, an aberrant gut microbiome has been associated with type 1 diabetes 57, 58 .…”