Serum Antibodies in First-Degree Relatives of Patients with IBD: A Marker of Disease Susceptibility? A Follow-Up Pilot-Study after 7 Years

Abstract

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.

Preclinical disease and preventive strategies in IBD: perspectives, challenges and opportunities

“…However, the significance and predictive value of these findings and of these biomarkers need to be demonstrated in appropriately powered longitudinal cohorts. For example, one study following 102 FDRs over a period of 7 years did not find any correlation between FDRs’ seropositivity and development of IBD 74. Likewise, in a prospective follow-up of multiplex families, none of the families where incident cases occurred during follow-up expressed an excess of genetic or serological markers 54…”

" Familial and ethnic risk in inflammatory bowel disease"

“…Indeed, several studies focusing on healthy relatives of patients with IBD have found that a subset of IBD relatives display altered intestinal permeability, elevated fecal calprotectin, positive antimicrobial markers, alterations in markers of innate and acquired immunity, or an altered microbiome [ 3 , 83 - 89 ]. Unfortunately, the predictive value of these biomarkers in assessing who will develop disease seems to be low [ 51 , 86 ]. For example, one study that followed 102 FDRs over a period of 7 years did not find any correlation between FDRs’ seropositivity for antimicrobial markers and their later development of IBD [ 86 ].…”

“…Unfortunately, the predictive value of these biomarkers in assessing who will develop disease seems to be low [ 51 , 86 ]. For example, one study that followed 102 FDRs over a period of 7 years did not find any correlation between FDRs’ seropositivity for antimicrobial markers and their later development of IBD [ 86 ]. Nevertheless, it is clear that study of unaffected FDRs provides an opportunity to investigate the earlier stages of disease pathogenesis, offering the possibility of identifying alterations that can predate disease and contribute to its development.…”

Recent Advances and Potential Multi-Omics Approaches in the Early Phases of Inflammatory Bowel Disease

“…Several serological markers have been identified that are present prior to the diagnosis of IBD, mainly through the presence of multiple anti-microbial antibodies (Figure 2, Table 1). These antibodies have also been detected in healthy first-degree relatives, with ASCA, pANCA, and anti-OmpC being more frequently reported, while ACCA, ALCA, and antiflagellin I2 and CBir1 have also been found in some reports [74][75][76]. The presence of these antibodies highlights the humoral immune dysregulation in at-risk populations, which may be linked to dysbiosis in some of these individuals.…”