Mucosal antibodies ininflammatory boweldisease aredirected against intestinal bacteria

Incontrast withnormalsubjects where IgAisthemainimmunoglobulin inthe intestine, patients withactive inflammatoryboweldisease (IBD)producehigh concentrations of IgG fromintestinal lymphocytes, buttheantigens atwhich theseantibodies are directedare unknown.Toinvestigate thespecificities oftheseantibodies mucosalimmunoglobulins wereisolated fromwashings takenat endoscopy from 21 control patients withirritable bowelsyndrome, 10 control patients withintestinal inflammationduetoinfection orischaemia, and51 patients withIBD:24 Crohn'sdisease (CD,15active, ninequiescent), 27ulcerativecolitis (UC,20active, seveninactive). TotalmucosalIgG was much higher (p<0001)in activeUC (median512 jxg/ml) andactive CD (256,ug/ml) than in irritable bowelsyndromecontrols (1.43 ,ug/ml), butnotsignificantly differentfromcontrols withnon-IBDintestinal inflammation (224,ug/ml). MucosalIgG boundtoproteins ofarangeofnon-pathogenic commensalfaecal bacteria inactive CD;this washigher thaninUC (p<0.01); andbothweresignificantly greater than controls withnon-IBDintestinal inflammation(CDp<0001,UC p<001)orIBS (p<0*001 CD andUC).ThismucosalIgG binding wasshownon westernblots and byenzymelinked immunosorbent assay (ELISA) tobeprincipally directed against thebacterial cytoplasmic rather thanthe membraneproteins. TotalmucosalIgA concentrations didnotdiffer between IBD andcontrols, buttheIgAtitres against faecal bacteria werelowerinUC than controls (p<0.01). Theseexperiments showthatthereisanexaggerated mucosal immuneresponseparticularly inactive CD butalsoinUC directed against cytoplasmicproteins ofbacteria withinthe intestinal lumen;thisimplies thatin relapse ofIBD thereisa breakdownof tolerance tothenormalcommensalflora ofthegut. (Gut1996; 38:365-375)