Role Of Intestinal Mucosal Barrier Function In Pathologic Mechanism Of Henoch-Schonlein Purpura In Children

Objective: Henoch-Schonlein purpura (HSP) is regarded as a specificimmune-mediated entity induced by environmental factors, and results from acomplex interplay between varying degrees of genetic susceptibility andenvironmental factors. Our desire is that this article will help us to furtherunderstand the complexity of this theory by clarifying the role of the intestinalmucosal barrier function in pathologic mechanism of HSP, while the intestinalmucosal barrier includes microbiological barrier, immunological barrier,mechanical barrier and chemical barrier. Recently, it is reported that intestinalluminal antigens absorbed through the gut may be involved. However, theintestinal mucosal barrier prevents the antigens from passing through,discriminates between pathogenic and nonpathogenic antigens and may formmucosal immunologic tolerance or allergic responses. This indicates that theintestinal microbiota composition, the intestinal mucosal immune componentsand the intestinal permeability play pivotal role in the development of a varietyof allergic and autoimmune diseases. Based on the above assumptions, weobserved the change of the intestinal flora, the level of secretoryimmunoglobulin A (sIgA) and the ratio of the excretion of lactulose/mannitol(L/M) in the children with HSP, which are respectively representative of theintestinal mucosal microbiological barrier, immunological barrier andmechanical barrier, and investigated how intestinal mucosal barrier functiondrives this critical illness, the effects of HPS on intestinal mucosal barrierfunction, and the complex crosstalk between these three portions of theintestinal mucosal barrier function, which provided a theoretical basis forabrogating the development of HSP through timely protecting intestinalmucosal barrier function at early stages.Methods:26patients (mean age6.04±1.75years,16boys and10girls) with HSP and20control subjects (mean age6.23±2.12years,13boys and7girls) were selected in the pediatric department of the Third Affiliated HospitalOf Hebei Medical University from August2011to February2012. HSP wasdefined according to the American college of rheumatology1990criteria forthe classification of Henoch-Schonlein purpura as the presence of two or moreof the following: age less than or equal to20years at disease onset, palpablepurpura, acute abdominal pain, and biopsy showing granulocytes in the wallsof small arterioles or venules. All subjects signed informed consent prior to thestart of the study, and the Ethics Committee of the Third Affiliated Hospital OfHebei Medical University agreed to this study. Fecal samples and urinarysamples were taken on the first day of treatment.16SrDNA fluorescentquantitative PCR was applied to analyze children intestinal bacteria. The ratioof the amount of Bifidobacterium/Escherichia coli (B/E) in feces representsthe ecotope of intestinal microecology. An decreased ratio of B/E is indicativeof intestinal dysbacteriosis. The level of sIgA in feces was quantified bystandard enzyme linked immunosorbent assay (ELISA). The intestinalmembrane permeability test was performed by directly measuring the ability ofmannitol (M) and lactulose (L)(nonmetabolized sugar molecules) to permeatethe intestinal mucosa by high performance liquid chromatography (HPLC). Mis easily absorbed and serves as a marker of transcellular uptake, while L is onlyslightly absorbed and serves as a marker for mucosal integrity. An increasedratio of the excretion of lactulose/mannitol (L/M) in urinary samples issuggestive of an increase in intestinal permeability. Both L/M ratio and B/Eratio were compared with that in the control group, respectively. Statisticalanalysis was performed with SPSS13.0software.Results: A total of46participants were studied that included26patientswith HSP (10girls,16boys; mean age6.04±1.75years; mean weight22.38±2.63kg) and20control subjects (7girls,13boys; mean age6.23±2.12years; mean weight23.49±3.24kg). There was no difference in sex, age, orweight between the two groups (HSP, controls)(P>0.05). Compared with thatin healthy control subjects, the quantity of bifidobacteria, B/E ratio and the level of sIgA in feces were all significantly lower in the children with HSP(P<0.05). There was no significant difference between the two groups in thequantity of Escherichia coli (P>0.05). However, the ratio of the excretion of Mand L and L/M ratio were significantly higher in the patients with HSP thanthat in healthy control subjects (P<0.05). In addition, analysis of the correlationamong B/E ratio, the level of sIgA in feces and L/M ratio showed that B/Eratio was positively correlated with the level of sIgA in feces, and negativelycorrelated with L/M ratio, and L/M ratio was negatively correlated with thelevel of sIgA in feces.Conclusion: The quantity of bifidobacteria and B/E ratio bothdecreased as compared to that in the control group, which suggestedintestinal dysbacteriosis in the children with HSP. What's more, the level ofsIgA in feces was lower than that in healthy control subjects, indicating thatthere was altered intestinal immune status in the children with HSP. Comparedwith healthy control children, L/M ratio increased in the children with HSP,indicating that intestinal permeability increased. In the case of HSP, there wasintestinal mucosal barrier dysfunction, including intestinal microbiologicalbarrier, immunological barrier and mechanical barrier. In addition, B/E ratio,the level of sIgA and L/M ratio were all correlated, which suggested that therewas a complex crosstalk among the intestinal microbiological barrier,immunological barrier and mechanical barrier. These three interrelatedportions of the intestinal mucosal barrier were involved in the pathologicmechanisms of HSP, respectively and synergistically. Herein, our current studyprovides a theoretical basis for abrogating the development of HSP throughprotecting intestinal mucosal barrier function at early stages.