Increased intestinal permeability in primary Sjögren's syndrome and multiple sclerosis

Abstract

There is increasing evidence suggesting a role of intestinal dysfunction in a number of autoimmune diseases. Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease with a documented increased level of intestinal inflammation, whereas multiple sclerosis (MS) is an organ-specific autoimmune disease known to exhibit increased intestinal permeability. In this study we determine to what extent intestinal inflammation, analysed by a faecal calprotectin ELISA, is accompanied by altered intestinal wall permeability, as measured by a lactulose and mannitol intestinal absorption assay. Intestinal permeability was increased in both pSS and MS patients, while faecal calprotectin was elevated in pSS but normal in MS. Our findings suggest different mechanisms mediating a leaky gut in these two diseases: in pSS there is autoimmune attack directly on the intestinal wall; in MS, with autoimmunity being limited to the CNS, it may be due to a disturbed CNS regulation of enteric nerve function.

Keywords: Faecal calprotectin; Intestinal permeability; Lactulose/mannitol ratio; Multiple sclerosis; Primary Sjögren’s syndrome.

Fig. 1

(A) Lactulose/mannitol urine concentrations ratio serving as a measure of intestinal permeability. The red line indicates the cut off. (B) Faecal calprotectin serving as a measure of intestinal inflammation. The red line indicates the level of 100 ​μg/g clinically used as a marker of intestinal inflammation in inflammatory bowel disease. Boxes represent values between quartiles 1 and 3, and a thick line indicates the median. Whiskers show the max and min values located above the top or below the bottom of the box, respectively, within a 1.5 interquartile distance. Circles denote outliers values located outside a 1.5 interquartile distance, and stars denote outliers located outside a 3 interquartile distance. Two extreme primary Sjögren’s syndrome outliers at 1113 and 2037 ​μg/g are not shown, but are included in the calculation of the box and whiskers. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2

Scatterplot with the results on lactulose/mannitol ratio and faecal calprotectin displayed for each individual primary Sjögren’s syndrome patient. Note that the Y-axis is split at 400 ​μg/g faecal calprotectin, in order for two extreme outliers to be displayed.