Pancreatic Autoantibodies in Inflammatory Bowel Disease

Joossens, Sofie; Vermeire, Séverine; Steen, Kristel Van; Godefridis, Godelieve; Claessens, Greet; Pierik, Marie J.; Vlietinck, Robert; Aerts, Raymond; Rutgeerts, Paul; Bossuyt, Xavier

doi:10.1097/00054725-200411000-00012

Cited by 55 publications

(47 citation statements)

References 29 publications

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“…The specificity for CD in the present study compared to both control groups was as high as 92%-95% with a strong positive likelihood ratio of 5.14 -8.77 against controls. However, a more recent study from Belgium found a much higher prevalence (22.2%) of PAB in UC, 35 in agreement with findings from the present study (22.7%). Consequently, the specificity for CD in the present study compared to UC decreased to 76%-77%.…”

Section: Discussionsupporting

confidence: 93%

Pancreatic Autoantibodies Are Associated with Reactivity to Microbial Antibodies, Penetrating Disease Behavior, Perianal Disease, and Extraintestinal Manifestations, But Not with NOD2/CARD15 or TLR4 Genotype in a Hungarian IBD Cohort

Lakatos¹,

Altorjay²,

Szamosi³

et al. 2009

Inflammatory Bowel Diseases

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Section: Discussionsupporting

confidence: 93%

Pancreatic Autoantibodies Are Associated with Reactivity to Microbial Antibodies, Penetrating Disease Behavior, Perianal Disease, and Extraintestinal Manifestations, But Not with NOD2/CARD15 or TLR4 Genotype in a Hungarian IBD Cohort

Lakatos¹,

Altorjay²,

Szamosi³

et al. 2009

Inflammatory Bowel Diseases

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“…Serum reactivity against mycobacterial antigens has also been correlated with human autoimmune diseases including Crohn's disease (13). Moreover, pancreatic antibodies are associated with Crohn's disease (9).…”

Section: Discussionmentioning

confidence: 99%

Humoral Immune Responses of Type 1 Diabetes Patients to Mycobacterium avium subsp. paratuberculosis Lend Support to the Infectious Trigger Hypothesis

Sechi

Rosu

Pacifico

et al. 2008

Clin Vaccine Immunol

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Mycobacterium avium subsp. paratuberculosis is a zoonotic pathogen whose association with Crohn's disease in humans is under scrutiny. The objective of this work was to investigate its association with other chronic diseases such as type 1 diabetes mellitus (T1DM), where the involvement of a persistent pathogen such as M. avium subsp. paratuberculosis could be the trigger. For this purpose, 59 diabetic patients and 59 healthy controls were investigated for the presence of antibodies against two recombinant proteins of M. avium subsp. paratuberculosis and the whole-cell lysate. Extremely significant humoral immune responses to recombinant heparin binding hemagglutinin and glycosyl transferase proteins and the whole-cell lysates of M. avium subsp. paratuberculosis bacilli were observed in T1DM patients and compared to those of healthy controls. Finding evidence of M. avium subsp. paratuberculosis involvement in T1DM is perhaps a novel finding that might serve as a foundation stone in establishing an infectious etiology for T1DM.Immune-related disorders are frequently rampant in both developed and developing countries. It is speculated that such diseases probably reflect and connect to long-term effects of a change in lifestyle and thereby a reduced exposure to certain bacteria that have been inherently associated with human societies during most of mammalian evolution (3,17). A very important group of bacteria among these organisms is saprophytic mycobacteria, which trigger regulatory immune cell populations (3, 17) such as cytokine-secreting and antigenpresenting cells. These immune cell populations are probably the deterrent to some autoimmune diseases such as type 1 (insulin-dependent) diabetes mellitus (T1DM).T1DM constitutes interactions of polygenic traits with notwell-known environmental factors, and it is not known what triggers autoimmunity to self-antigens such as those expressed in the pancreatic islets of Langerhans cells (5, 11). Drinking of cow's milk in childhood is assumed to be a risk factor for the development of this disease (17). The role of mycobacterial proteins that cross-react with epitopes of human cell surface molecules has been explored (3, 5).Human populations that lived hygienic lifestyles and therefore remained "sanitized" for decades might react aggressively to exposure to certain microbial communities such as Mycobacterium avium subsp. paratuberculosis. Due to the expansion of the dairy industry in developed countries as a result of modern animal breeding, the exposure of human populations to M. avium subsp. paratuberculosis has increased. Sardinia, Italy, is one such example, where intensive sheep farming is practiced and the sheep population constitutes more than four times the existing human population of this Mediterranean island.M. avium subsp. paratuberculosis bacilli have been notoriously known to trigger molecular mimicry (15,23). It has long been a belief that genetic susceptibilities, epitope homologies, and endemic bacterial load in the environment might support the case ...

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“…In this context, it is interesting to note, that almost all type 2 PAB positive sera also show a weak type 1 PAB staining by IIF at least on human pancreas [43]. Furthermore, type 2 PAB does not seem to differentiate CrD patients from UC patients whereas type 1 PAB appears to be able do so [32]. In fact, anti-GP2 reactivity is not universally found in all PAB-positive patients.…”

Section: Identification Of Crd-specific Pancreatic Autoantigensmentioning

confidence: 93%

“…A multicenter study involving 109 CrD patients from five university hospitals in France and one in Luxemburg, failed to identify an association between PABs and clinical features of the disease except of a relationship between the presence of the autoantibodies and an early disease onset [30]. An earlier study from Leuven including 169 CrD patients established a significant negative association of stricturing disease behavior and PAB seropositivity [32].…”

Section: Autoimmunity In Crohn's Diseasementioning

confidence: 95%

Crohn’s disease specific pancreatic antibodies: clinical and pathophysiological challenges

Roggenbuck¹,

Reinhold

Schierack

et al. 2014

Clinical Chemistry and Laboratory Medicine

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Crohn's disease (CrD) and ulcerative colitis (UC) are the main inflammatory bowel diseases (IBD). IBDspecific humoral markers of autoimmunity in the form of autoantibodies have been reported first in the late 1950s by demonstrating the occurrence of autoimmunity in UC, while humoral autoimmunity in CrD can be traced back to the 1970s. Ever since, the pathophysiological role of autoimmune responses in IBDs has remained poorly understood. Notwithstanding, autoreactive responses play a major role in inflammation leading to overt IBD. In CrD, approximately 40% of patients and < 20% of patients with UC demonstrate loss of tolerance to antigens of the exocrine pancreas. Glycoprotein 2 (GP2) has been identified as a major autoantigenic target of the so-called pancreatic antibodies. The previously unsolved contradiction of pancreatic autoreactivity and intestinal inflammation in IBD was elucidated by demonstrating the expression of GP2 at the site thereof. Intriguingly, GP2 has been reported to be a receptor on microfold cells of intestinal Peyer's patches, which are believed to represent the origin of CrD inflammation. The development of immunoassays for the detection of antibodies to GP2 has paved the way to investigate the association of such antibodies with the clinical phenotype in CrD. Given the recently discovered immunomodulating role of GP2 in innate and adaptive intestinal immunity, this association can shed further light on the pathophysiology of IBD. In this context, the association of anti-GP2 autoantibodies as novel CrD-specific markers with the clinical phenotype in CrD will be discussed in this review.

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Pancreatic Autoantibodies in Inflammatory Bowel Disease

Cited by 55 publications

References 29 publications

Pancreatic Autoantibodies Are Associated with Reactivity to Microbial Antibodies, Penetrating Disease Behavior, Perianal Disease, and Extraintestinal Manifestations, But Not with NOD2/CARD15 or TLR4 Genotype in a Hungarian IBD Cohort

Pancreatic Autoantibodies Are Associated with Reactivity to Microbial Antibodies, Penetrating Disease Behavior, Perianal Disease, and Extraintestinal Manifestations, But Not with NOD2/CARD15 or TLR4 Genotype in a Hungarian IBD Cohort

Humoral Immune Responses of Type 1 Diabetes Patients to Mycobacterium avium subsp. paratuberculosis Lend Support to the Infectious Trigger Hypothesis

Crohn’s disease specific pancreatic antibodies: clinical and pathophysiological challenges

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