Mucosal reactivity to cow's milk protein in coeliac disease

Abstract

Patients with coeliac disease (CD) on a gluten-free diet may still have gastrointestinal symptoms. On clinical grounds cow's milk (CM) protein sensitivity may be suspected. Here, using rectal protein challenge, we investigated the local inflammatory reaction to gluten and CM protein in adult patients with CD in remission. Rectal challenges with wheat gluten and dried CM powder were performed in 20 patients with CD and 15 healthy controls. Fifteen hours after challenge the mucosal reaction was recorded by the mucosal patch technique with measurements of local release of neutrophil and eosinophil granule constituents; myeloperoxidase (MPO) and eosinophil cationic protein (ECP). We measured the mucosal production of nitric oxide (NO) simultaneously. Six of the patients who reacted to CM were also challenged with alpha-lactalbumin and casein. In 18 of 20 patients gluten challenge induced neutrophil activation defined as increased MPO release and increased NO synthesis. Ten of these 20 patients showed a similarly strong inflammatory reaction to CM challenge. Six of the CM sensitive patients were challenged with specific CM proteins: casein and alpha-lactalbumin. Casein, in contrast to alpha-lactalbumin, induced an inflammatory response similar to that produced by CM. A mucosal inflammatory response similar to that elicited by gluten was produced by CM protein in about 50% of the patients with coeliac disease. Casein, in particular, seems to be involved in this reaction.

Fig. 1

The mucosal patch technique for measurement of the inflammatory condition of the rectal mucosa is illustrated. The instrument used is a plastic catheter with a silicon balloon at the end of the catheter, with three patches of highly absorptive cellulose material attached to the balloon. The figure illustrates when the instrument is positioned in the rectal ampulla and the balloon is inflated with air (60–80 ml), allowing the patches to be in contact with the mucosa. After 20 min the balloon is deflated and the air is collected in glass syringe for analysis of nitric oxide (NO). After removal of the catheter the patches are cut off and immediately placed in 2 ml of 0·3% N-cetyl-N,N,N-trimethyl ammonium bromide (CTAB) to extract the contents.

Fig. 2

Increase in rectal luminal nitric oxide (ΔNO) and rectal mucosal concentration of myeloperoxidase (MPO) (ΔMPO) in patients with coeliac disease (n = 20) 15 h after rectal milk challenge. The level of two standard deviations (s.d.) above mean of the control subjects (n = 15) is marked by a line.

Fig. 3

Six coeliac patients reactive to cow's milk protein accepted further investigation and were challenged with casein and five of them also accepted challenge with α-lactalbumin. The figure illustrates rectal luminal nitric oxide (NO) and rectal mucosal concentration of myeloperoxidase (MPO) 15 h after rectal challenge with casein and α-lactalbumin.