Serum antibodies in first-degree relatives of patients with IBD: A marker of disease susceptibility? A follow-up pilot-study after 7 years

Introduction: Various disease-specific serum antibodies were described in patients with inflammatory bowel disease and their yet healthy first-degree relatives. In the latter, serum antibodies are commonly regarded as potential markers of disease susceptibility. The present long-term follow-up study evaluated the fate of antibody-positive first-degree relatives. Patients and Methods: 25 patients with Crohn's disease, 19 patients with ulcerative colitis and 102 first-degree relatives in whom presence of ASCA, pANCA, pancreatic- and goblet-cell antibodies had been assessed were enrolled. The number of incident cases with inflammatory bowel disease was compared between antibody-positive and antibody-negative first-degree relatives 7 years after storage of serum samples. Results: 34 of 102 (33%) first-degree relatives were positive for at least one of the studied serum antibodies. In the group of first-degree relatives, one case of Crohn's disease and one case of ulcerative colitis were diagnosed during the follow-up period. However, both relatives did not display any of the investigated serum antibodies (p = 1). Discussion: The findings of our pilot study argue against a role of serum antibodies as a marker of disease susceptibility in first-degree relatives of patients with inflammatory bowel disease. However, these data have to await confirmation in larger ideally prospective multicenter studies before definite conclusions can be drawn

Serum antibodies in first-degree relatives of patients with IBD: A marker of disease susceptibility? A follow-up pilot-study after 7 years

Introduction: Various disease-specific serum antibodies were described in patients with inflammatory bowel disease and their yet healthy first-degree relatives. In the latter, serum antibodies are commonly regarded as potential markers of disease susceptibility. The present long-term follow-up study evaluated the fate of antibody-positive first-degree relatives. Patients and Methods: 25 patients with Crohn's disease, 19 patients with ulcerative colitis and 102 first-degree relatives in whom presence of ASCA, pANCA, pancreatic- and goblet-cell antibodies had been assessed were enrolled. The number of incident cases with inflammatory bowel disease was compared between antibody-positive and antibody-negative first-degree relatives 7 years after storage of serum samples. Results: 34 of 102 (33%) first-degree relatives were positive for at least one of the studied serum antibodies. In the group of first-degree relatives, one case of Crohn's disease and one case of ulcerative colitis were diagnosed during the follow-up period. However, both relatives did not display any of the investigated serum antibodies (p = 1). Discussion: The findings of our pilot study argue against a role of serum antibodies as a marker of disease susceptibility in first-degree relatives of patients with inflammatory bowel disease. However, these data have to await confirmation in larger ideally prospective multicenter studies before definite conclusions can be drawn

Prevalence and diagnostic role of antineutrophil cytoplasmic antibodies in inflammatory bowel disease.

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA) are of proven diagnostic value in a variety of vasculitides, where they are also thought to play a pathogenic role. ANCA has also been detected in the serum of patients with idiopathic inflammatory bowel disease (IBD), both ulcerative colitis (UC) and Crohn's disease (CD), and primary sclerosing cholangitis (PSC) with or without concomitant IBD. Although the prevalence in PSC and UC is reported to be up to 85%, a much lower prevalence of around 10-20% has been reported in CD. AIM: To determine ANCA prevalence in a group of British patients with IBD and evaluate their use as a serological marker to distinguish between UC and CD. METHODS: A total of 99 UC-only patients (44 males, median age 50) and 41 CD patients (11 males, median age 47) were tested for ANCA using an alkaline phosphatase technique at a 1:5 serum dilution. Controls were other diarrhoeal diseases including 17 coeliac disease (4 males, median age 41), 23 irritable bowel syndrome (5 males, median age 42), 5 infectious colitis (2 male, median age 64) and 36 healthy volunteers (13 males, median age 43). RESULTS: ANCA was detected in 42/99 (42.4%) UC patients but in only 2/41 (5%) CD (P < 0.0001). All ANCA were perinuclear in distribution. No ANCA was detected in the control sera. The sensitivity of the test for the diagnosis of UC was 42% with a specificity of 98%. In patients with UC, no association was found between presence of ANCA and age, sex, disease extent, treatment or activity. However, ANCA-positive UC patients had longer median duration of disease (50 months vs. 29 months, P = 0.037). Both CD ANCA-positive patients had colonic involvement, but one also had ileal disease. Both had inactive disease and one was on mesalazine. CONCLUSIONS: ANCA is highly specific for UC and may be a helpful diagnostic test in distinguishing UC from CD and other diarrhoeal illnesses. Although ANCA positivity may reflect disease heterogeneity within UC, no association with clinical features or treatment of UC was demonstrated and it is therefore unlikely to play a pathogenic role. The correlation with disease duration needs further investigation

Absence of antineutrophil cytoplasmic antibodies in relatives of UK patients with primary sclerosing cholangitis and ulcerative colitis.

OBJECTIVE: Perinuclear antineutrophil cytoplasmic antibodies (ANCA) have been reported in patients and relatives of patients with ulcerative colitis and primary sclerosing cholangitis, suggesting that ANCA may be a genetic marker of disease susceptibility. The reported frequency of ANCA in relatives has varied greatly, between 0 and 30%. We therefore studied the prevalence of ANCA in unaffected first-degree relatives of British patients with primary sclerosing cholangitis and ulcerative colitis. DESIGN: Thirty-six patients with ulcerative colitis, 33 with primary sclerosing cholangitis and 187 relatives were studied. Ninety-seven relatives were from the primary sclerosing cholangitis proband and 90 were from the ulcerative colitis proband. As an environmental control, 32 spouses were included: 14 from the primary sclerosing cholangitis group and 18 from the ulcerative colitis group. Eighteen healthy volunteers were additional controls. METHODS: ANCA was detected using immunoalkaline phosphatase method. RESULTS: Only 3 of 97 (3%) of the primary sclerosing cholangitis proband relatives had ANCA. One of these had ulcerative colitis, one had rheumatoid arthritis and the third systemic lupus erythematosus. Both rheumatoid arthritis and system lupus erythematosus are known to exhibit ANCA. All other sera were negative. CONCLUSION: ANCA was found only in patients with primary cholangitis and ulcerative colitis and not in their healthy first-degree relatives. ANCA is therefore not a genetic marker for increased disease susceptibility to primary sclerosing cholangitis or ulcerative colitis in the British population