Anti-neutrophil cytoplasmic antibodies in inflammatory bowel disease with special attention for IgA-class antibodies

Perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) of the IgG class have been reported in inflammatory bowel disease, mainly in ulcerative colitis. Since this disease affects the gastrointestinal tract, we determined whether IgA class ANCA were present in inflammatory bowel disease. We used an indirect immunofluorescence assay for IgG and IgA ANCA testing. Sera from 34 patients with Crohn's disease and 29 patients with ulcerative colitis were collected together with clinical and laboratory data. We found IgA class ANCA of a perinuclear type in 52% of patients with ulcerative colitis and in 9% of Crohn's disease patients. There was a significant association between the presence of IgA ANCA and the occurrence of blood in the feces in the ulcerative colitis group (P = 0.03). IgG ANCA was found in 56% of patients with ulcerative colitis and in 7% of patients with Crohn's disease. Because of partial overlap between IgG and IgA ANCA positivity, the sensitivity of ANCA testing in ulcerative colitis increased from 56% up to 78% by combining IgG and IgA assays. In conclusion, IgA ANCA occurs with a high prevalence in ulcerative colitis. Moreover there is a possible relationship between IgA ANCA and disease activity in ulcerative colitis.     

Neutrophil signaling alteration: an adverse inflammatory response after burn shock

BACKGROUND: Perinuclear antineutrophil cytoplasmic antibodies occur frequently in adult patients with chronic pouchitis after colectomy and ileal pouch-anal anastomosis for ulcerative colitis. The purpose of the study was to determine the prevalence of perinuclear antineutrophil cytoplasmic antibodies and cytoplasmic antineutrophil cytoplasmic antibody in children and adolescents who undergo colectomy and ileal pouch-anal anastomosis for ulcerative colitis and familial adenomatous polyposis. METHODS: Five groups of children and adolescents (age, <20 years) were studied, with the following histories: acute pouchitis and history of ulcerative colitis; chronic pouchitis and history of ulcerative colitis; pouchitis with Crohn's disease features and a history of ulcerative colitis; no pouchitis and a history of ulcerative colitis; and familial adenomatous polyposis, with or without pouchitis. Antineutrophil cytoplasmic antibody levels and titers were detected in postoperative sera by enzyme-linked immunosorbent assay, and positive results were subtyped by indirect immunofluorescence. RESULTS: The frequency of perinuclear antineutrophil cytoplasmic antibodies and cytoplasmic antineutrophil cytoplasmic antibody in patients with a history of ulcerative colitis were 67% and 15%, compared with a 0% presence in patients with familial adenomatous polyposis (p < 0.001). There was no significant correlation between the frequency of perinuclear antineutrophil cytoplasmic antibodies and ulcerative colitis patient subgroups (patients with and without pouchitis, 66% and 75%). Similarly, there was no significant correlation between the frequency of cytoplasmic antineutrophil cytoplasmic antibodies among ulcerative colitis patient subgroups (patients with and without pouchitis, 19% and 8%). The frequency of cytoplasmic antineutrophil cytoplasmic antibody in patients with Crohn's disease features (50%), was increased, but this difference was not significant. CONCLUSIONS: There is a high frequency of perinuclear antineutrophil cytoplasmic antibodies in children and adolescents who undergo ileal pouch-anal anastomosis for ulcerative colitis, whether or not they have pouchitis. The frequency of cytoplasmic antineutrophil cytoplasmic antibody is lower in this patient population. Additional studies will be required to determine whether the presence of cytoplasmic antineutrophil cytoplasmic antibody is associated with the postoperative development of features of Crohn's disease.     

The majority of myeloid-antigen-positive (My+) childhood B-cell precursor acute lymphoblastic leukaemias express TEL-AML1 fusion transcripts

BACKGROUND & AIMS: Crohn's disease and ulcerative colitis show a familial aggregation. In both diseases, anti-goblet cell autoantibodies (GABs) have been described. The aim of this study was to define the role of GABs in the pathogenesis of inflammatory bowel disease. METHODS: The study population comprised 61 patients with ulcerative colitis, 76 patients with Crohn's disease, 101 first-degree relatives of patients with ulcerative colitis, and 105 first-degree relatives of patients with Crohn's disease. Thirty-five patients with infectious enterocolitis and 56 healthy unrelated subjects served as controls. Autoantibodies were detected by indirect immunofluorescence. RESULTS: Thirty-nine percent of patients with ulcerative colitis (24 of 61) and 30% of patients with Crohn's disease (23 of 76) were positive for GABs. GABs were detected in 21% (21 of 101) of first-degree relatives of patients with ulcerative colitis and in 19% (20 of 105) of first-degree relatives of patients with Crohn's disease. In patients with infectious enterocolitis and in healthy controls, GABs were seen in 3% (1 of 35) and 2% (1 of 56), respectively. The differences between control groups and both groups of patients or their first-degree relatives were significant. CONCLUSIONS: The high prevalence in first-degree relatives suggests that GABs may represent a marker characterizing susceptibility to inflammatory bowel disease.     

Incidence of inflammatory bowel diseases in the department of Puy-de-D?me in 1993 and 1994. EPIMICI. Epidémiologie des Maladies Inflammatoires Cryptogenetiques de l'Intestin group

The aim of this prospective epidemiological study was to investigate the incidence of Inflammatory Bowel Disease in the Puy-de-D?me county using the same methodology as EPIMAD's registry. METHODS: From 01/01/93 to 31/12/94, each gastroenterologist (n = 22) collected patients consulting for the first time with clinical symptoms compatible with inflammatory bowel disease. Data were reported on a questionnaire by an interviewer practitioner. The final diagnosis of Crohn's disease and ulcerative colitis was made in a blind manner by two expert gastroenterologists and recorded according to the Calkin's criteria as definite, probable, or possible diagnosis, or unclassifiable chronic colitis or acute colitis. RESULTS: 167 new cases were identified: 112 (67.1%) inflammatory bowel disease for the combined group of definite and probable cases with 79 Crohn's disease (70.5%), 29 ulcerative colitis (25.9%) of which 11 ulcerative proctitis (37.9%), 4 unclassifiable chronic colitis (3.6%) and 55 acute colitis (32.9%). The crude and age-adjusted incidence (per 10(5)/year) was respectively 6.6 and 5.7 for Crohn's disease and 2.4 and 1.9 for ulcerative colitis. The highest age-specific incidence rate for Crohn's disease was between 40-49 years (14.1) and for ulcerative colitis between 80-89 years (6.8). The female/male ratio was 0.8 for Crohn's disease and 1.1 for ulcerative colitis. The median age at the time of diagnosis was 42.6 years for Crohn's disease and 35.3 years for ulcerative colitis. CONCLUSIONS: These preliminary findings revealed a high incidence of Crohn's disease and low of ulcerative colitis in this county. However, these results must be managed carefully because these data were recorded only on two years and the inflammatory bowel disease classified possible and acute colitis require a follow-up.     

Medial collateral knee ligament healing. Combined medial collateral and anterior cruciate ligament injuries studied in rabbits

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA), particularly perinuclear ANCA (p-ANCA), have been found more frequently in sera from patients with ulcerative colitis (UC) than in sera from Crohn's disease (CD) or unclassified enterocolitis (UE) patients. This 2-center study examined sera from 102 pediatric patients with inflammatory bowel disease (IBD) to evaluate their diagnostic value and assess their relationship with disease features, distribution, activity and treatment. METHODS: The serum ANCA of 102 children with IBD were measured: 33 UC, 64 CD and 5 UE with various disease locations and degrees of activity. The mean age at the onset of symptoms was 10.7 years (1 to 16.3 years). Sera from 26 unaffected first degree relatives and 20 children without IBD were also investigated. ANCA were detected using indirect immunofluorescence of ethanol-fixed granulocytes. RESULTS: There were ANCA in the sera of 24/33 children with UC (73%), 9/64 with CD (14%) and 4/5 with UE (80%). p-ANCA were more frequent than cytoplasmic-ANCA in positive sera: UC = 67%, CD = 57% and UE = 75%. The presence of ANCA was 73% sensitive and 81% specific for a diagnosis of UC, compared to other IBD (p < 0.001). Three children with proved sclerosing cholangitis associated with UC were all positive. There was no link between ANCA-positive sera and disease activity, or other endoscopic or clinical criteria. ANCA were detected in 4/26 first degree relatives (15%) and in 1/20 control subjects (5%). CONCLUSIONS: Because of their sensitivity and specificity, ANCA may be helpful in the clinical assessment of patients with IBD, and especially those with UC. However, there is no link between the pressure of p-ANCA and the site of UC or its activity, so that it cannot be used to monitor medical treatment or surgical indications.     

Recognition of bactericidal/permeability-increasing protein by perinuclear anti-neutrophil cytoplasmic antibody-positive sera from ulcerative colitis patients: prevalence and clinical significance

BACKGROUND: The aim of this study was to evaluate a) the role of bactericidal/permeability-increasing protein (BPI) as a possible antigen determining perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) reactivity in ulcerative colitis and b) the prevalence and clinical correlates of anti-BPI antibodies in patients with ulcerative colitis on the basis of their p-ANCA status. METHODS: p-ANCA and anti-BPI antibodies were evaluated by means of indirect immunofluorescence and enzyme-linked immunosorbent assay methods in a group of 112 ulcerative colitis patients (including 42 patients subjected to proctocolectomy) well defined as far as their clinical features and p-ANCA status. RESULTS: Anti-BPI antibodies were detected in 24% of non-operated patients and were significantly more frequent in p-ANCA-positive patients (32% versus 5% in p-ANCA-negative patients; P < 0.015). The prevalence of anti-BPI antibodies was similar in non-operated and operated patients and was high in men, in patients with an extensive and aggressive disease, and in patients developing pouchitis after surgery. CONCLUSIONS: These data indicate that BPI is a neutrophil antigen frequently recognized by p-ANCA-positive ulcerative colitis sera. The presence of anti-BPI antibodies appears to identify further immunologic and clinical heterogeneity in ulcerative colitis.     

Treatment of refractory rapid cycling bipolar disorder with risperidone

BACKGROUND: There is evidence for a hypercoagulable state in inflammatory bowel disease (IBD), and small vessel thrombosis has been identified in the bowel of patients with Crohn's disease, suggesting thrombosis as a possible etiologic factor. Activated protein C (APC) resistance is the most common inherited disorder leading to thrombosis and accounts for 30% to 40% of episodes of idiopathic venous thrombosis. METHODS: The prevalence of APC resistance was studied in 23 patients with IBD (17 with Crohn's disease, 6 with ulcerative colitis) and in 11 control subjects with recurrent abdominal pain or celiac disease, using an APC resistance screening method. RESULTS: One patient with Crohn's disease had a positive screen result, two patients (one with Crohn's, one with ulcerative colitis) had borderline results, and results in all of the control subjects were normal. One patient with Crohn's disease had a history of a thromboembolic event but had a normal screen result. CONCLUSIONS: Activated protein C resistance does not seem to play a major role in the etiology of the hypercoagulable state in inflammatory bowel disease.     

Direct detection of Mycobacterium tuberculosis complex and M. avium complex in tissue specimens from cattle through identification of specific rRNA sequences

BACKGROUND: In many cases inflammatory bowel disease is accompanied by extraintestinal manifestations. This results in lowering of live quality. The aim of this study was to gather data retrospectively about initial symptoms, extraintestinal manifestations and course of pregnancy in a large unselected population with inflammatory bowel disease in South Germany. PATIENTS AND METHODS: Data from 1975 to 1989 (392 patients) were analyzed and partially compared with data from 1992 to 1995 (211 patients). RESULTS: Patients with Crohn's disease in average have been 25 years old at the time point of initial symptoms, whereas the age of ulcerative colitis patients was 30 years (p < 0.0001). The number of Crohn's disease patients with a long interval between initial symptoms and diagnosis (> 1 year) was significantly decreased in the second population (50% vs 38%; p < 0.05). Dominant initial symptoms in Crohn's disease were indisposition, abdominal pain and nonbloody diarrhea in contrast to ulcerative colitis which manifested mostly with bloody diarrhea. Extraintestinal manifestations occurred in 76% of patients with Crohn's disease and 64.6% with ulcerative colitis. Complications during the course of pregnancy have been detected in 40.5% in Crohn's disease and 60% in ulcerative colitis. CONCLUSION: A better knowledge of initial symptoms and extraintestinal manifestations in inflammatory bowel disease can help to decrease the interval between initial symptoms and the diagnosis. Pregnancy in patients with inflammatory bowel disease needs to be treated with special care.     

Incidence of inflammatory bowel disease in northern France (1988-1990)

There were no data concerning the incidence of inflammatory bowel disease (IBD) in France. The aim of this study was to investigate the incidence of Crohn's disease and ulcerative colitis in northern France. This prospective population based study was realised through the gastroenterologists of the region Nord-Pas de Calais and the Somme Department. Each gastroenterologist referred patients consulting for the first time with clinical symptoms compatible with IBD. Data were collected by an interviewer practitioner present at the gastroenterologist's consulting room. Two independent expert gastroenterologists assessed each case in a blind manner and made a final diagnosis of Crohn's disease, ulcerative colitis, ulcerative proctitis, or unclassifiable chronic colitis. From 1988 to 1990, 1291 cases of IBD were recorded: 674 (52%) Crohn's disease, 466 (36%) ulcerative colitis including 162 proctitis (35%), and 151 (12%) unclassifiable chronic colitis. The mean annual incidence was 4.9 per 100,000 for Crohn's disease and 3.2 for ulcerative colitis. The sex ratio F/M was 1.3 for Crohn's disease and 0.8 for ulcerative colitis. The highest age specific incidence rate for Crohn's disease was between 20 and 29 years: 13.1 for women and 9.8 for men. The highest age specific incidence rate for ulcerative colitis was between 20 and 39 years: 5.5 for women and 6.5 for men. This first French prospective study has shown an incidence rate for Crohn's disease comparable with that seen in north European studies but lower than that seen for ulcerative colitis. These results could be related to the different environmental factors or the genetic background of the population studied, or both.     

Measurement of rectal blood flow by laser Doppler flowmetry in inflammatory bowel disease

BACKGROUND/AIMS: Vascular alterations have been suggested as pathogenic factors in inflammatory bowel disease, particularly Crohn's disease. The aim of our study was to assess rectal blood flow in patients with active inflammatory bowel disease involving the rectum. METHODOLOGY: Endoscopic measurement of rectal blood flow was performed by laser Doppler flowmetry in 45 subjects divided into three groups: healthy controls, ulcerative colitis and rectal Crohn's disease. RESULTS: Rectal perfusion was found to be significantly impaired in patients with ulcerative colitis, but not in those with Crohn's colitis. CONCLUSIONS: Our results confirm the role of local ischemia in ulcerative colitis, but do not support the theory that vascular factors play a key role in the pathogenesis of Crohn's disease.     

The extra-intestinal complications of Crohn's disease and ulcerative colitis: a study of 700 patients

The records of a series of 700 patients with inflammatory bowel disease, 498 with Crohn's disease and 202 with ulcerative colitis, have been analyzed to determine the relative incidence and characteristic features of their extra-intestinal manifestations. The group with Crohn's disease included 62 with colitis, 223 with ileocolitis, and 213 with regional enteritis. A consideration of the clinical patterns and an understanding of their pathophysiology suggested a subdivision into two main groups: one "colitis related" and one related to the pathophysiology of the small nonspecific third group. Group A, colitis related, comprises joint, skin, mouth, and eye disease. The complications might be immunologically determined, were closely associated with active inflammation, and often responded to medical or surgical treatment of the underlying bowel disease. They occurred in 36% of the entire series of patients: joints were involved in 23%, skin in 15%, and mouth and eye each in 4%. Pyoderma gangrenosum was observed most often in ulcerative colitis and erythema nodosum most often in granulomatous colitis. The incidence of Group A complications was higher in disease involving the colon (42%) than in disease restricted exclusively to the small bowel (23%). There were interrelationships among the various members of Group A, with multiple manifestations occurring in a third of affected patients. Group B, related to small bowel pathophysiology, includes malabsorption, gallstones, kidney stones, and non-calculous hydronephrosis and hydroureter. Disorders in this group were generally related to the severity of the disease in the small bowel and tended to persist even in the absence of active inflammation. In contrast to Group A, this group occurred most frequently in small bowel disease, and least in colonic disease. Malabsorption was virtually confined to the patients with small bowel disease (10% incidence), while gallstones and renal stones were also both more frequent in Crohn's disease (11% and 9% respectively), the latter usually in association with small bowel resection or ileostomy. Group C, found in a small percentage of patients, consists of nonspecific complications, including osteoporosis (3%), liver disease (5%), peptic ulcer (10%), and amyloidosis (1%).     

Risk indicators for inflammatory bowel disease

We investigated the association between different risk indicators and inflammatory bowel disease in a case-control study based on the population of Stockholm County during 1980-1984. Information on physical activity, oral contraceptives, some previous diseases and childhood characteristics was collected using a postal questionnaire for 152 cases of Crohn's disease, 145 cases of ulcerative colitis, and 305 controls. The relative risk (RR) of Crohn's disease was inversely related to regular physical activity and estimated at 0.6 (95% CI: 0.4-0.9) and 0.5 (95% CI: 0.3-0.9) for weekly and daily exercise, respectively. Having psoriasis prior to the inflammatory bowel disease was associated with an increased relative risk of Crohn's disease (RR = 2.9, 95% CI: 1.1-7.9). Use of oral contraceptives was associated with an increased RR of 1.7 for both Crohn's disease and ulcerative colitis. Crohn's disease confined to the colon and total ulcerative colitis at diagnosis were most strongly associated with oral contraceptives.     

Correlation of a common mutation in the methylenetetrahydrofolate reductase gene with plasma homocysteine in patients with premature coronary artery disease

BACKGROUND: Recent clinical trials have demonstrated that methotrexate may have an important therapeutic role in the treatment of patients with inflammatory bowel disease, who are either refractory or intolerant to traditional medical therapy. The aim of this study was to evaluate the pharmacokinetics of low-dose oral methotrexate in patients with inflammatory bowel disease. METHODS: Methotrexate (12.5 mg) was given orally to nine patients with inflammatory bowel disease: five with Crohn's disease, and four with ulcerative colitis, and to six patients with rheumatoid arthritis who served as a control group. Blood samples were drawn at specific intervals to evaluate methotrexate plasma levels. RESULTS: Methotrexate was rapidly absorbed in all patients. Peak concentrations (Cmax) varied considerably, ranging from 0.25-0.87 micro M. The mean Cmax values were similar in all patient groups (0.59 +/- 0.12, 0.69 +/- 0.16 and 0.54 +/- 0.18 micro M, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean area under curve in 120 min (AUC0-120) was also similar in all patient groups (32.9 + 11.3, 43.6 + 9.9 and 41.8 + 14.9 ng.min/mL, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean time to reach Cmax, (tmax), varied between patient groups (84, 112 and 95 min, respectively, with a significant difference, P < 0.02, between the Crohn's disease and ulcerative colitis groups. A negative correlation was found between methotrexate dosage/kg and Cmax (r = -0.74) only in Crohn's disease patients but not in the other patient groups. CONCLUSIONS: Orally administered methotrexate is well absorbed in patients with inflammatory bowel disease including those with severe small bowel disease or resection. If methotrexate is proven to be effective in inflammatory bowel disease, it should be administered orally.     

The surgical management of nonspecific inflammatory bowel disease: a small personal experience

AIMS: To document the surgical management of patients with non specific inflammatory bowel disease managed in the colorectal service, University Department of Surgery, Wellington School of Medicine. METHODS: Retrospective analysis of patients managed between April 1975 and March 1990. RESULTS: Sixty five patients had inflammatory bowel disease. Twenty one (11 males) had ulcerative colitis and 44 (18 males) had Crohn's disease. There were no Maori. One hundred and twenty three operations were performed overall. Ten patients with ulcerative colitis were operated upon as emergencies. Five presented with fulminating disease. Six patients successfully underwent restorative proctocolectomy although one was subsequently thought to have had Crohn's disease. Overall there was one postoperative death. Crohn's disease patients underwent a total of 91 operations. Twenty nine operations were elective and 15 emergency during the first surgical admission. The commonest indication for surgery was stricture. The commonest operation performed was right hemicolectomy. Chest, wound and central line sepsis were the commonest postoperative problems. There were two postoperative deaths. Six patients favoured a series of relatively minor perineal operations to proctectomy. CONCLUSION: A cautious staged approach to the surgical management of inflammatory bowel disease patients resulted in only three deaths-an overall mortality rate of 4.6%. Accordingly we advocate a policy of expectant surgery to relieve symptoms or correct complications in patients with Crohn's disease. We believe that patients requiring surgery for ulcerative colitis should be offered the choice of either restorative proctocolectomy or panproctocolectomy and ileostomy.     

Familial empirical risks for inflammatory bowel disease: differences between Jews and non-Jews

The Jewish population has an increased frequency of inflammatory bowel disease compared with their non-Jewish neighbours. Genetic factors have been implicated in the aetiology of this disorder and may contribute to ethnic differences. This study determined the familial empirical risks for inflammatory bowel disease in the first degree relatives of inflammatory bowel disease probands (for both Jews and non-Jews) for the purpose of accurate genetic counselling and genetic analysis. A total of 527 inflammatory bowel disease patients from Southern California (291 Jews and 236 non-Jews) were questioned about inflammatory bowel disease in their first degree relatives (a total of 2493 individuals). Since inflammatory bowel disease has a variable and late age of onset, age specific incidence data were used to estimate the life time risks and to make valid comparisons between the different groups. In the first degree relatives of non-Jewish probands, the life time risks for inflammatory bowel disease were 5.2% and 1.6% when probands had Crohn's disease and ulcerative colitis respectively. These values were consistently lower than the corresponding risks for relatives of Jewish patients -7.8% and 4.5% for Crohn's disease and ulcerative colitis probands respectively (p value for comparison between Jews and non-Jews: 0.028; between ulcerative colitis and Crohn's disease: 0.005). These data provide the requisite basis for genetic counselling for these disorders in the white American population. In addition, these different empirical risks for relatives of Jewish and non-Jewish probands allow rejection of single Mendelian gene models for inflammatory bowel disease, but are consistent with several alternative genetic models.     

Surgery for inflammatory bowel disease in Singapore

Inflammatory bowel disease is uncommon in Asians and reports of surgery in these populations are rare. Eighty-two patients with inflammatory bowel disease were seen in the Department of Colorectal Surgery over a five-year period (1989-1994). Twenty-three patients underwent surgery for their disease. There were 12 males and 11 females with 16 Chinese, 4 Indians and 3 Malays. Twelve had Crohn's disease and 11, ulcerative colitis. The majority of patients with Crohn's disease had emergency surgery for bleeding, perforation, abdominal masses and intestinal fistulae. Fifty percent of these had the diagnosis made intraoperatively or post-operatively. Surgery for ulcerative colitis was indicated because of multiple relapses, non-response to medical treatment, side effects of therapy or malignant change. The median age at surgery of patients with Crohn's disease and ulcerative colitis was 39 years (range 24-84) and 40 (range 18-60) respectively. The median follow-up was 22.4 months (range 9-50). The results of surgical therapy in these patients show that surgery when indicated can be done with minimum morbidity and mortality.     

Detection of anti-colon antibodies in inflammatory bowel disease using human cultured colonic cells

BACKGROUND: Investigation of anti-colon antibodies may be simplified if a sensitive method and homogeneous source of antigen were available. AIMS: To examine the anti-colon antibody response using human colonic carcinoma cell lines as antigen. Subjects: Patients with inflammatory bowel disease and other gastrointestinal disorders and healthy controls were studied. METHODS: Comparative enzyme linked immunosorbent assays (ELISAs) were performed to assess the value of whole Caco-2, HT-29, and LS-180 cells as antigen. The antigenic determinants of the immune response were characterised by western blot analysis. RESULTS: Sera demonstrated immunoreactivity against each of the cell lines, but different epitopes were recognised. Applying whole Caco-2 cells as antigen in an ELISA, the prevalence of anti-colon antibodies was significantly greater in patients with ulcerative colitis (36%) than Crohn's disease (13%), other gastrointestinal disorders (13%) and healthy controls (0) (p<0. 05). The immune response was not associated with one predominant antigen. CONCLUSIONS: Fixed whole cell ELISA is a simple and feasible method for studying the anti-colon antibody response. This response is non-specific, being directed against multiple antigens, and is likely to be an epiphenomenon of inflammatory bowel disease, more so for ulcerative colitis than Crohn's disease.     

Diagnostic accuracy of serological assays in pediatric inflammatory bowel disease

BACKGROUND & AIMS: Accurate serological assays are desirable for the diagnosis of inflammatory bowel disease (IBD) types in the pediatric age group. The aim of this study was to test the diagnostic accuracy of modified assays for perinuclear (p) antineutrophil cytoplasmic antibodies (ANCAs) and anti-Saccharomyces cerevisiae antibodies (ASCAs) in patients with pediatric ulcerative colitis (UC) and Crohn's disease (CD) and in those without IBD. METHODS: With observers blinded to patients' diagnoses, serum specimens were analyzed for immunoglobulin (Ig) A and IgG ASCAs and ANCAs by enzyme-linked immunosorbent assay. The perinuclear location of ANCAs visualized by indirect immunofluorescence was confirmed by its disappearance after administration of deoxyribonuclease. RESULTS: IgA and IgG ASCA titers were significantly greater and highly specific for CD (95% for either, 100% if both positive). pANCA was 92% specific for UC and absent in all non-IBD controls. The majority of patients with CD positive for pANCA had a UC-like presentation. Disease location, duration, activity, complications, and treatment with immunosuppressive drugs did not have an impact on the ASCA or pANCA assay results. After resection, UC patients remained pANCA positive, in contrast to patients with CD, in whom ASCA titers decreased toward normal values postoperatively. CONCLUSIONS: ASCA and pANCA assays are highly disease specific for CD and UC, respectively. These serological tests can assist clinicians in diagnosing and categorizing patients with IBD and may be useful in making therapeutic decisions.     

Epitope mapping of cytochrome P450cam (CYP101)

OBJECTIVE: A retrospective study of women with inflammatory bowel disease, aged 16-45 years during the 20-year period 1967-1986, was carried out in North East Scotland. METHOD: Five-hundred and three women were identified: 15 patients had died from unrelated causes and 22 had emigrated, but 409 of the remaining 466 patients (88%) replied to the study questionnaire. RESULTS: Women with ulcerative colitis and Crohn's disease had normal fertility when compared with the general population of north east Scotland. However, unresolved infertility problems were more frequent in women who had undergone surgery for inflammatory bowel disease compared with those who had not (12% vs. 5% for Crohn's disease; 25% vs. 7% for ulcerative colitis). Disease relapse rates did not increase in pregnancy. CONCLUSIONS: Overall, at conception women with active disease were as likely to have a normal full-term pregnancy as those in remission. However, spontaneous abortion occurred in five (36%) pregnancies of women who had undergone previous surgery for Crohn's disease and had evidence of recurrent disease. Three of these pregnancies were associated with active disease.     

Antineutrophil cytoplasmic antibodies in inflammatory bowel disease: diagnostic tool or research procedure?

Antineutrophil cytoplasmic antibodies, initially detected in the sera of patients with Wegener's granulomatosis and other forms of systemic vasculitides, have also been observed in patients with inflammatory bowel disease, with a higher prevalence in ulcerative colitis. In this study, we investigated the prevalence of these antibodies in the sera of 42 patients with ulcerative colitis and 48 patients with Crohn's disease, and the possible correlations with disease activity and extent, extraintestinal complications, and therapy. Antineutrophil cytoplasmic antibodies were found in 30 out of the 42 patients with ulcerative colitis (71.4%); only 16 out of the 48 patients (33.3%) with Crohn's disease were positive (p < 0.001), and the prevalent pattern was perinuclear. No correlations with disease activity and extent, extraintestinal complications, or surgical or medical treatment were found. Our data indicate that in the case of inflammatory bowel disease, the search for antineutrophil cytoplasmic antibodies still remains a research procedure and cannot be used for clinical diagnosis.