Lack of circulating immune complexes in inflammatory bowel disease

Multi-organ involvement and especially extraintestinal manifestations have suggested an immune complex-mediated pathogenesis of ulcerative colitis and Crohn's disease. Using various techniques controversial data have been reported on the incidence and levels of circulating immune complexes and their correlation to clinical presentation. Sera of 131 patients with inflammatory bowel disease (78 Crohn's disease, 53 ulcerative colitis) representing a wide spectrum of disease activity, treatment and presence or absence of extraintestinal manifestations were tested for circulating immune complexes using Raji cell indirect immunofluorescence assay, Raji cell radioimmunoassay, C1q solid phase assay and polyethylene glycol precipitation coupled with measurements of optical density and subsequent immunoelectrophoresis or radial immunodiffusion. Circulating immune complexes in low concentrations were observed in a small number of patients with inflammatory bowel disease, the frequency and concentrations being slightly higher in patients with Crohn's disease than in those with ulcerative colitis. No association of concentrations of circulating immune complexes with disease activity or presence of extraintestinal manifestations could be demonstrated. These data do not support the claim for a major role of circulating immune complexes in the pathogenesis of inflammatory bowel disease.     

Distinct elevation of levels of anti-Caenorhabditis elegans antibody in sera of patients with inflammatory bowel disease

Dysregulation of immune responses to intestinal exogenous antigens contributes to the pathogenesis of inflammatory bowel disease, but the specific antigen responsible for the pathogenesis of inflammatory bowel disease is unknown. We measured serum antibody titers against Caenorhabditis elegans antigens. Immunoglobulin G (IgG) and IgG subclass anti-C. elegans antibodies in serum samples from 29 patients with ulcerative colitis, 30 patients with Crohn's disease, 7 patients with intestinal Beh?et's disease, and 11 healthy controls were measured by enzyme-linked immunosorbent assay. Serum IgG and IgG2 antibody titers against C. elegans were significantly higher in patients with inflammatory bowel disease than in controls. Antibody levels were not affected by age, gender, disease activity, extent of disease, or small bowel involvement. The anti-C. elegans antibody titer was significantly lower in patients with Crohn's disease taking mesalazine or sulfasalazine than in patients not taking these drugs. The increased immune responses to C. elegans found in patients with inflammatory bowel disease reflect dysregulated immune responses to enteric antigens, which might play a role in the pathogenesis of inflammatory bowel disease.     

Immune functions in inflammatory bowel and coeliac diseases

Different immune functions of 10 patients with glutein-sensitive enteropathy (GSE), 9 with Crohn's disease (CD), 11 with ulcerative colitis (UC) and 13 healthy controls were characterized. The numbers of suppressor T cells in GSE were comparable to those of the controls; otherwise, the lymphocyte subpopulations were decreased in these bowel diseases. In the whole-blood cultures, the lymphocyte proliferative responses to PHA were normal in the bowel diseases, but the responses to Con A were decreased in CD. In cultures with D-penicillamine, the inhibition of the helper effect of CD patients was more pronounced in PHA-stimulated cultures than in Con A-stimulated cultures. The total Ig and IgA production did not markedly differ among the groups. PWM-induced IgM secretion was significantly decreased in GSE, CD and UC, and IgG secretion in CD and UC, as compared to controls. In GSE, an increased Con A inducible suppressor cell activity was observed in the IgM production. Altogether, no clear-cut immunological imbalance was detected in any of the bowel diseases; this in agreement with previous works. However, there are some differences in the regulatory cell balance among the patients with GSE, CD and UC. The determination of lymphocyte proliferative responses to PHA and Con A together with D-penicillamine seems to provide a new immunological criterium for distinguishing between Chrohn's disease and ulcerative colitis.     

Humoral immune system and ulcerative colitis activity. II. Complement level

C4, C3 and C5 levels and the complement hemolytic activity were analysed in 84 ulcerative colitis patients and correlated with activity, extension and duration of the disease, with the presence of extraintestinal manifestation, and with therapeutic effects. The elevation of C3 was observed in both mild active and in severe colitis. Only C3 correlated with disease activity and with C-reactive protein level. On the other hand, C4 and C5 levels were significantly decreased in the active disease extended to the left side or to total great bowel. The importance of these findings is discussed. No significant connection of the examined complement components with duration, therapy and extraintestinal manifestation was observed. A trend to increase the complement hemolytic activity in severe colitis was noted. Our study of complement and its components activity suggests the secondary role of analysed parameters in pathogenesis of UC and clinical usefulness of C3 level as an indicator of the disease activity.     

溃疡性结肠炎患者血清25(OH)维生素D水平与疾病活动性的相关性

目的检测溃疡性结肠炎患者血清25(OH)维生素D水平,并分析25(OH)维生素D水平与疾病活动性的关系,探讨其临床意义。方法选择40例溃疡性结肠炎患者和30例健康对照者为研究对象,采用ELISA法检测溃疡性结肠炎患者和健康体检者血清中25(OH)维生素D水平,应用Mayo评分法对UC病人的疾病活动度进行分级,将维生素D水平与UC患者临床资料以及疾病活动度进行相关性分析。结果溃疡性结肠炎患者血清25(OH)维生素D水平(15.8±12.3)ng/ml明显低于健康对照组(42.5±26.7)ng/ml,p0.05,血清25(OH)维生素D水平与患者年龄、性别、病程、是否吸烟、抗生素的应用、5-氨基水杨酸的应用及非甾体类抗炎药的应用无相关性,但与皮质类固醇激素的应用及溃疡性结肠炎的活动性相关。结论溃疡性结肠炎患者低储备维生素D水平与疾病活动性及皮质类固醇激素的应用相关。     

High Frequency of Mononuclear Myeloid-Derived Suppressor Cells is Associated with Exacerbation of Inflammatory Bowel Disease

Exacerbation and relapse of inflammatory bowel disease (IBD) is associated with reduced antibacterial immunity and increased immune regulatory activity, but the source of increased immune regulation during episodes of disease activity is unclear. Myeloid-derived suppressor cells (MDSCs) are a cell type with a well-recognized role in limiting immune reactions. MDSC function in IBD and its relation to disease activity, however, remains unexplored. Here we show that patients with either ulcerative colitis (UC) or Crohn's disease (CD) have high peripheral blood levels of mononuclear MDSCs. Especially exacerbation of disease is associated with higher levels of mononuclear MDSC counts compared with those in remission of disease. Interestingly, chronic experimental colitis in mice coincides with increased MDCS mobilization. Thus, our results suggest that mononuclear MDCS are endogenous antagonists of immune system functionality in mucosal inflammation and the depression of antibacterial immunity associated with exacerbation of disease might involve increased activity of the MDSC compartment.     

Diagnosis and classification of ulcerative colitis

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease (IBD) characterised by superficial mucosal ulceration, rectal bleeding, diarrhoea, and abdominal pain. In contrast to Crohn's disease (CrD), UC is restricted to the colon and the inflammation is limited to the mucosal layer. Classic UC affects the colon in a retrograde and continuous fashion starting from the rectum and extending proximally. Dependent on the anatomic extent of involvement, UC can be classified as proctitis, left-sided colitis, or pancolitis. Inflammatory arthropathies and primary sclerosing cholangitis (PSC) are the most common and clinically most important extraintestinal manifestations of UC. The aetiopathogenesis of UC is incompletely understood, but immune-mediated mechanisms are responsible for dysregulated immune responses against intraluminal antigens in genetically predisposed individuals. The diagnosis is based on the history, as well as clinical, radiological, endoscopic and histological features. Autoantibodies, mainly antineutrophil cytoplasmic antibodies (ANCA) and anti-goblet cell antibodies (GAB) may be helpful in the early diagnosis of UC and in differentiating it from CrD.     

Promoter methylation of protease-activated receptor (PAR2) is associated with severe clinical phenotypes of ulcerative colitis (UC)

Tryptase acting at protease-activated receptor 2 (PAR2) contributes to the pathogenesis of Inflammatory bowel diseases (IBDs). DNA methylation has been shown to be an important mechanism in gene silencing. We attempted to clarify the relationship between the promoter methylation of PAR2 and ulcerative colitis (UC). 84 UC patients enrolled in the study. UC patients were classified by disease behavior, severity and extent of disease. For rectal inflammatory mucosal specimens from all the patients, and normal terminal ileum from 23 patients, promoter methylation of PAR2 gene was quantified by digital densitographic analysis following to methylation-specific polymerase chain reaction (MSP). The mean methylation levels of the PAR2 gene in all 84 subjects was 38.4 ± 19.6%. Although mean methylation levels in rectal inflammatory mucosa, and paired normal terminal ileum did not vary, methylation levels of PAR2 gene was significantly higher in total colitis than rectal colitis (total colitis vs. rectal colitis; 42.9 ± 19.6% vs. 34.5 ± 18.9%, P = 0.046). The higher methylation levels were also associated with Steroid-dependent (P = 0.002) and refractory (P = 0.007) UC. Our data suggest that PAR2 methylation status in rectal mucosa correlates with more severe disease phenotypes of UC.     

Biochemical analysis of enzymic markers of inflammation in rectal biopsies from patients with ulcerative colitis and Crohn''s disease.

Rectal biopsies were collected from control subjects, patients with ulcerative colitis both active and quiescent, and from patients with Crohn's disease, both with and without rectal involvement, as judged by histological assessment. Tissue homogenates were assayed for neutrophil (vitamin B12 binding protein, myeloperoxidase, lysozyme) and lymphocyte (5' nucleotidase) selective markers. Patients with acute but not those with quiescent colitis had striking increases of the neutrophil markers. Neither patient group with ulcerative colitis showed a change in the lymphocyte marker enzyme activity. Patients with Crohn's disease involving the rectum showed significant, but less marked, increases in the activity of the neutrophil markers that were found in active ulcerative colitis. Patients with Crohn's disease, not involving the rectum, showed normal or reduced levels of neutrophil markers. Patients with Crohn's disease, both those with and without rectal involvement, had increased activities of the lymphocyte selective marker. This distinguishes this inflammatory response from that of ulcerative colitis and provides further biochemical evidence of abnormalities in apparently uninvolved mucosa from Crohn's patients.     

Type I Allergy to Normal Cellular Constituents in Chronic Inflammatory Bowel Disease?

The possibility of autoimmune type I reactions to cellular constituents was investigated in 22 patients with ulcerative colitis, 12 with Crohn's disease, and in 22 healthy volunteers. Nuclear components and colon mucosa fragments were tested as potential antigens by the basophil histamine release technique. One of 12 patients with ulcerative colitis responded to sonicated leukocyte nuclei and one of 12 patients with Crohn's disease responded to both nuclei and RNA. Increased serum levels of total IgE and antinuclear antibodies of IgE class were found in one and three of the 24 patients, respectively. Histamine release caused by colon mucosa fragments was not observed in a separate study consisting of 10 ulcerative colitis patients and 10 healthy volunteers. Autoimmune type I allergy to cellular constituents does not seem to be of significance for chronic inflammatory bowel disease and thus could not explain the involvement of tissue mast cells and eosinophils in this condition.     

Diagnostic problems and advances in inflammatory bowel disease.

This review summarizes current diagnostic problems and advances with regard to patterns of inflammation and dysplasia in ulcerative colitis and Crohn's disease. Ulcerative colitis and Crohn's disease have a variety of characteristic but non-specific pathologic features. In approximately 5% of inflammatory bowel disease cases, a definite diagnosis of ulcerative colitis or Crohn's disease cannot be established, in which case the term "indeterminate" colitis is used. Most cases of indeterminate colitis are related to fulminant colitis, a condition in which the classic features of ulcerative colitis or Crohn's disease may be obscured by severe ulceration with early superficial fissuring ulceration, transmural lymphoid aggregates, and relative rectal sparing. Approximately 20% of patients with indeterminate colitis develop severe pouch complications, which is intermediate in frequency between ulcerative colitis (8-10%) and Crohn's disease (30-40%). In order to establish a diagnosis of ulcerative colitis or Crohn's disease, it is important to evaluate pathologic material in conjunction with clinical, laboratory, radiologic, and endoscopic features and to recognize the variety of changes that may be seen in fulminant ulcerative colitis. There are a number of exceptions to the classic principles of inflammatory bowel disease pathology that may lead to diagnostic confusion. For instance, apparent skip lesions on biopsy analysis may occur in patients with ulcerative colitis in the following settings; long term oral or topical therapy, focal ascending colon, cecum and/or appendiceal involvement in patients with left sided ulcerative colitis, upper gastrointestinal involvement in patients with ulcerative colitis, and at initial presentation of ulcerative colitis in pediatric patients. In all of these circumstances, the finding of patchy disease and/or rectal sparing should not be misinterpreted as either evidence against a diagnosis of ulcerative colitis, or as representing skip areas characteristic of Crohn's disease. Patients with ulcerative colitis and Crohn's disease are at increased risk for the development of dysplasia and carcinoma. Recent studies suggest that given a similar duration and extent of disease, patients with Crohn's disease have a similar risk of dysplasia and cancer as patients with ulcerative colitis. Dysplasia in ulcerative colitis may be classified as flat or elevated (dysplasia associated lesion or mass [DALM]). Patients with flat high grade dysplasia are generally treated with colectomy. However, there is recent evidence to suggest that patients with flat low grade dysplasia, particularly if detected at the time of initial endoscopic exam, or if its multifocal or synchronous, should also be treated with colectomy. Elevated lesions in ulcerative colitis (DALM) are subdivided into "adenoma-like" and "non-adenoma-like" lesions based on their endoscopic appearance. Recent data suggests that adenoma-like lesions, regardless of the grade of dysplasia, or the location of the lesion (i.e., inside or outside areas of established colitis) may be treated adequately by polypectomy if there are no other areas of flat dysplasia in the patient. Although there are some histologic and molecular features that can help differentiate sporadic adenomas from adenoma-like polypoid dysplastic lesions related to ulcerative colitis, none of these adjunctive techniques can help distinguish these lesions definitively in any single patient. Patients with a non-adenoma-like DALM, (irregular, broad based, or strictured lesion) should be treated with colectomy because of the high probability of adenocarcinoma. The surveillance and treatment options for patients with flat and elevated dysplasia in ulcerative colitis are reviewed in detail.     

Interleukin-2- and interferon-gamma-secreting T cells in normal and diseased human intestinal mucosa.

A sensitive reverse haemolytic plaque assay to detect lymphokine-secreting T cells, and Northern blot analysis to detect expression of lymphokine messenger RNA (mRNA) were used to study interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) production in the mucosa of children with Crohn's disease or ulcerative colitis (UC), and in histologically normal mucosa from patients without inflammatory bowel disease. In the mucosa of most patients with UC and control patients, IL-2- and IFN-gamma-secreting cells were absent or were present at only low levels. In contrast, in mucosa from patients with Crohn's disease, lymphokine-secreting cells were readily detectable (3-18%). IFN-gamma mRNA was detected by Northern blot analysis in 5/6 Crohn's tissues, but only in 1/5 UC samples and none of nine samples of control mucosa. These studies reveal an ongoing cell-mediated immune response in the mucosa in Crohn's disease.     

Inflammatory bowel disease in children--clinical, endoscopic, radiologic and histopathologic investigation.

This paper reviews our five years' clinical experience (1987 to 1991) of 22 patients with inflammatory bowel disease (IBD). There were 12 patients with Crohn's disease and 10 patients with ulcerative colitis. The mean age at diagnosis was 8.7 years (2 to 14 years). Clinical impressions before referral were chronic diarrhea in 11, irritable bowel syndrome in 5, colon polyp in 4, lymphoma in 3, intestinal tuberculosis in 2, amoebic colitis in 2, ulcerative colitis in 2 children and other diseases. The mean interval from the onset of symptoms to the diagnosis of IBD was 18 months. Diagnosis of Crohn's disease was delayed for more than 13 months in 8 (67%), whereas that of ulcerative colitis was delayed for more than 13 months in 4 (40%). Diarrhea (50%), abdominal pain (36%) and rectal bleeding (36%) were the three most frequent presenting complaints of IBD. Moderately severe abdominal pain was a more common chief complaint in Crohn's disease (58%) than in ulcerative colitis (10%). Hematochezia (90% vs 17%) and moderately severe diarrhea (90% vs 75%) were more common gastrointestinal manifestations in ulcerative colitis than in Crohn's disease. The associated extraintestinal manifestations were oral ulcer in 7, arthralgia in 11 and arthritis in 4, skin lesions in 2, eye lesions in 2 and growth failure in 9 patients. Of 12 children with Crohn's disease, granuloma was found in 5, aphthous ulcerations in 8, cobble stone appearance in 8, skip area or asymmetric lesions in 6, transmural involvement in 7, and perianal fistula in 3. Among 10 children with ulcerative Colitis, there were crypt abscess in 8, granularity or friability in 10 and rectosigmoid ulcerations with purulent exudate in 8 children. The main sites of involvement in children with Crohn's disease were both the small and large bowels in 7 (58%), small bowel only in 2 (16%), and colon only in 3 (25%). Terminal ileum involvement was seen in 75% of Crohn's disease cases. The main sites of involvement in children with ulcerative colitis were total colon in 4 (40%), up to the splenic flexure in 2 (20%), rectosigmoid in 3 (30%) and rectum only in one (10%). Medical treatment including sulfasalazine, and systemic or topical steroid was administered initially in most patients. Seven of 12 patients with Crohn's disease and 2 of 10 patients with ulcerative colitis were operated on.(ABSTRACT TRUNCATED AT 400 WORDS)     

Correlation of Serum Vitamin A Levels with Disease Activity Indices and Colonic IL‐23R and FOXP3 mRNA Expression in Ulcerative Colitis Patients

Genome‐wide association studies have identified IL‐23 receptor (IL‐23R) as a susceptibility locus for the pathogenesis of ulcerative colitis (UC), which is characterized by exaggerated Th2/Th17 response. Studies have shown that vitamin A (VA) reduces disease progression by promoting FOXP3? T cells and curbing Th17 cells. In this study, we explored the association of colonic IL‐23R and FOXP3 expression in fifty‐one UC patients (23 in remission and 28 with active disease) with serum VA levels and disease activity. We observed that decreased serum VA levels were associated with increased disease activity. However, there was no significant difference in mucosal IL‐23R and FOXP3 expression in UC patients with moderate–to‐severe disease activity compared to those in remission. Also, no significant correlation was drawn between serum VA levels and mucosal IL‐23R and FOXP3 expression. Our study suggests that even after an established role of VA in inhibiting Th17 responses in mice models and humans, serum VA levels and disease activity do not correlate with FOXP3 and IL‐23R expression in colonic mucosa of UC patients.     

Increased production of soluble TLR2 by lamina propria mononuclear cells from ulcerative colitis patients

Toll-like receptor 2 (TLR2) is a type I pattern recognition receptor that has been shown to participate in intestinal homeostasis. Its increased expression in the lamina propria has been associated with the pathogenesis in inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn's disease (CD). Recently, soluble TLR2 (sTLR2) variants have been shown to counteract inflammatory responses driven by the cognate receptor. Despite the evident roles of TLR2 in intestinal immunity, no study has elucidated the production and cellular source of sTLR2 in IBD. Furthermore, an increase in the population of activated macrophages expressing TLR2 that infiltrates the intestine in IBD has been reported. We aimed first to assess the production of the sTLR2 by UC and CD organ culture biopsies and lamina propria mononuclear cells (LPMCs) as well as the levels of sTLR2 in serum, and then characterize the cell population from lamina propria producing the soluble protein. Mucosa explants, LPMCs and serum were obtained from UC, CD patients and control subjects. The level of sTLR2 was higher in conditioned media from organ culture biopsies and LPMCs from UC patients in comparison to CD and controls. Moreover, an inverse correlation between the content of intestinal and serum sTLR2 levels was observed in UC patients. Additionally, when characterizing the cellular source of the increased sTLR2 by LPMCs from UC patients, an increase in TLR2(+)/CD33(+) cell population was found. Also, these cells expressed CX3CR1, which was related to the increased levels of intestinal FKN in UC patients, suggesting that a higher proportion of TLR2(+) mononuclear cells infiltrate the lamina propria. The increased production of sTLR2 suggests that a differential regulating factor of the innate immune system is present in the intestinal mucosa of UC patients.     

Lymphoid follicular hyperplasia--a distinctive feature of diversion colitis

Diversion colitis refers to the inflammatory changes that occur in the defunctioned segment of the large intestine following diversion of the faecal stream. We report the histological features in the defunctioned rectums from seven patients: one each with severe constipation and Beh?et's disease, two with Crohn's disease with rectal sparing and three with ulcerative colitis. The appearances of diversion colitis in a previously normal rectum are compared with diversion colitis with superimposed inflammatory bowel disease. Lymphoid follicular hyperplasia was found in all cases. This was marked in patients with inflammatory bowel disease, with or without initial rectal involvement. Other changes comprised surface epithelial degeneration and ulceration, mucosal inflammation including crypt abscesses, and crypt branching. Inflammatory and crypt changes were mild, except in ulcerative colitis where changes were marked and resembled those of the proximal colon. Lymphoid hyperplasia is a distinctive feature in diversion colitis. The term follicular proctitis, previously used to indicate chronic ulcerative colitis exclusively, should be re-examined.     

Lymphoid follicular hyperplasia–a distinctive feature of diversion colitis

Diversion colitis refers to the inflammatory changes that occur in the defunctioned segment of the large intesting following diversion of the faecal stream. We report the histological features in the defunctioned rectums from seven patients: one each with severe constipation and Behcet's disease, two with Crohn's disease with rectal sparing and three with ulcerative colitis. The appearances of diversion colitis in a previously normal rectum are compared with diversion colitis with superimposed inflammatory bowel disease. Lymphoid follicular hyperplasia was found in all cases. This was marked in patients with inflammatory bowel disease. with or without initial rectal involvement. Other changes comprised surface epithelial degeneration and ulceration, mucosal inflammation including crypt abscesses, and crypt branching. Inflammatory and crypt changes were mild, except in ulcerative colitis where changes were marked and resembled those of the proximal colon. Lymphoid hyperplasia is a distinctive feature in diversion colitis. The term follicular proctitis, previously used to indicate chronic ulcerative colitis exclusively, should be re-examined.     

In vitro testing of immunoresponsiveness in patients with inflammatory bowel disease: prevalence and relationship to disease activity immunoresponsiveness in IBD.

Abnormalities in the numbers and function of thymus and function of thymus-derived and bone marrow-derived lymphocytes (T and B cells) and K cells were determined in sixty-nine consecutive patients with Crohn's disease or ulcerative colitis. Rosetting techniques to identify subpopulations of lymphocytes showed a significant decrease in E-rosettes (T cells) and significant increase in EA- and EAC-rosettes (B cells) in patients with inflammatory bowel disease when compared to normals. In vitro lymphocyte transformation responses to mitogens and antigens were depressed to a variable degree. Mean levels of K cell activity were not significantly different from normal controls. A considerable degree of individual variation was noted in all groups. When the results of each groups were considered, none of the laboratory variables correlated with the site, duration or activity of disease, therapy, presence of iron deficiency anemia, weight loss or hypoalbuminaemia. Thus, in vitro evidence of abnormal immune responses in patients with inflammatory bowel disease cannot be directly related to clinical or laboratory variables and probably reflects a multi-factorial aetiology.     

Morphology of colorectal lymphoid aggregates in cancer, diverticular and inflammatory bowel diseases.

The present study compares the characteristics of colorectal lymphoid aggregates in patients with carcinoma, diverticular disease, Crohn's disease, or ulcerative colitis of the large bowel. A total of 77 patients (41 colorectal cancer, 27 diverticular disease, six ulcerative colitis, three Crohn's disease) undergoing colorectal resection were included. Acetic acid staining, hematoxylin and eosin staining, CD3, CD20, and MIB1 immunostaining were employed in order to assess density, diameter, subepithelial or basal location, cellular profile, and proliferation of lymphoid aggregates in normal-appearing and actively inflamed large bowel. In normal-appearing tissue, mean density of lymphoid aggregates was lower in patients with ulcerative colitis and Crohn's disease than in those with colorectal cancer or diverticular disease. A larger mean diameter of aggregates was observed in patients with Crohn's disease. In inflammatory bowel diseases, a marked increase of the mean density of lymphoid aggregates was observed in actively affected specimens. In Crohn's disease more than in ulcerative colitis, the aggregates had a predominant basal or transmural distribution. In diverticular disease, active inflammation determined a less significant increase of subepithelial aggregates harboring a lower proportion of germinal centers. No significant variations of CD3, CD20, and MIB1 were recorded among the four disease groups. The lymphoid aggregate derangements observed not only in the actively affected mucosa but also in the unaffected colorectal lining of patients with Crohn's disease and ulcerative colitis support a relevant involvement of lymphoid aggregate system in the pathogenesis of inflammatory bowel diseases.     

IgA autoreactivity: a feature common to inflammatory bowel and connective tissue diseases

The immunopathogenic mechanisms in inflammatory bowel disease (IBD) are not yet fully established. The aim of this study was to determine the profile and magnitude of IgA and IgG autoantibodies in IBD patients. The autoantigen profile defined by IgA and IgG antibodies from 24 IBD (14 Crohn's disease CD], 10 ulcerative colitis UC]), three coeliac, 12 connective tissue disease (CTD) patients and 10 healthy individuals was studied in human cellular extracts by Western blotting. The magnitude of the IgA and IgG1-4 subclass responses was measured by ELISA. IBD patients could not be distinguished from healthy individuals on the basis of IgG autoantibodies to Western blotted proteins. IgG subclass analysis indicated no clear bias towards Th1 or Th2 immune responses in IBD or CTD. In accordance with previous work, we found that IgA autoreactivity was strongest in coeliac disease patients. Unexpectedly, IBD as well as CTD patients exhibited strong IgA autoantibody reactivities to components of similar molecular weights (16-80 kD) in intestinal and non-intestinal epithelial cell lines. Our data indicate immunopathogenic similarities between IBD and CTD.