CUZD1 and Anti-CUZD1 Antibodies as Markers of Cancer and Inflammatory Bowel Diseases

Liaskos, Christos; Rigopoulou, Eirini I.; Orfanidou, Timoklia; Bogdanos, Dimitrios P.; Papandreou, Christos N.

doi:10.1155/2013/968041

Cited by 16 publications

(13 citation statements)

References 101 publications

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“…CUZD1 (CUB and zona pellucida-like domain-containing protein 1) was induced in the cecal tissue of chickens inoculated with microbiota of 4- but not 40-week-old donor hens. There is little functional information with CUZD1 except for the fact that anti-CUZD1 antibodies are used as a marker of inflammatory bowel disease in humans [ 24 ]. ISG12-2 was induced by microbiota inoculation and was also expressed at lower levels in germ-free compared with conventional chickens.…”

Section: Discussionmentioning

confidence: 99%

Transient and Prolonged Response of Chicken Cecum Mucosa to Colonization with Different Gut Microbiota

et al. 2016

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In this study we determined protein and gene expression in the caeca of newly hatched chickens inoculated with cecal contents sourced from hens of different ages. Over 250 proteins exhibited modified expression levels in response to microbiota inoculation. The most significant inductions were observed for ISG12-2, OASL, ES1, LYG2, DMBT1-L, CDD, ANGPTL6, B2M, CUZD1, IgM and Ig lambda chain. Of these, ISG12-2, ES1 and both immunoglobulins were expressed at lower levels in germ-free chickens compared to conventional chickens. In contrast, CELA2A, BRT-2, ALDH1A1, ADH1C, AKR1B1L, HEXB, ALDH2, ALDOB, CALB1 and TTR were expressed at lower levels following inoculation of microbiota. When chicks were given microbiota preparations from different age donors, the recipients mounted differential responses to the inoculation which also differed from the response profile in naturally colonised birds. For example, B2M, CUZD1 and CELA2A responded differently to the inoculation with microbiota of 4- or 40-week-old hens. The increased or decreased gene expression could be recorded 6 weeks after the inoculation of newly hatched chickens. To characterise the proteins that may directly interact with the microbiota we characterised chicken proteins that co-purified with the microbiota and identified a range of host proteins including CDD, ANGPTL6, DMBT1-L, MEP1A and Ig lambda. We propose that induction of ISG12-2 results in reduced apoptosis of host cells exposed to the colonizing commensal microbiota and that CDD, ANGPTL6, DMBT1-L, MEP1A and Ig lambda reduce contact of luminal microbiota with the gut epithelium thereby reducing the inflammatory response.

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Section: Discussionmentioning

confidence: 99%

Transient and Prolonged Response of Chicken Cecum Mucosa to Colonization with Different Gut Microbiota

et al. 2016

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“…Elevated transcription of GP2 mRNA and translation of GP2 being a 78 kDa GPIanchored molecule with N-linked carbohydrates in intestinal biopsy samples was only shown for patients with CD in contrast to patients with UC [58]. Unlike for GP2, evidence for the expression of the other PAb target CUZD1 in the intestine and a possible immunomodulating role thereof is still lacking [106].…”

Section: Gp2 As An Autoantigenic Target In Psc-indication Of Microbiamentioning

confidence: 99%

The search for the Holy Grail: autoantigenic targets in primary sclerosing cholangitis associated with disease phenotype and neoplasia

Lopens

Krawczyk

Papp

et al. 2020

Autoimmun Highlights

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Unlike in other autoimmune liver diseases such as autoimmune hepatitis and primary biliary cholangitis, the role and nature of autoantigenic targets in primary sclerosing cholangitis (PSC), a progressive, chronic, immune-mediated, life threatening, genetically predisposed, cholestatic liver illness, is poorly elucidated. Although anti-neutrophil cytoplasmic antibodies (ANCA) have been associated with the occurrence of PSC, their corresponding targets have not yet been identified entirely. Genome-wide association studies revealed a significant number of immune-related and even disease-modifying susceptibility loci for PSC. However, these loci did not allow discerning a clear autoimmune pattern nor do the therapy options and the male gender preponderance in PSC support a pathogenic role of autoimmune responses. Nevertheless, PSC is characterized by the co-occurrence of inflammatory bowel diseases (IBD) demonstrating autoimmune responses. The identification of novel autoantigenic targets in IBD such as the major zymogen granule membrane glycoprotein 2 (GP2) or the appearance of proteinase 3 (PR3) autoantibodies (autoAbs) have refocused the interest on a putative association of loss of tolerance with the IBD phenotype and consequently with the PSC phenotype. Not surprisingly, the report of an association between GP2 IgA autoAbs and disease severity in patients with PSC gave a new impetus to autoAb research for autoimmune liver diseases. It might usher in a new era of serological research in this field. The mucosal loss of tolerance against the microbiota-sensing GP2 modulating innate and adaptive intestinal immunity and its putative role in the pathogenesis of PSC will be elaborated in this review. Furthermore, other potential PSC-related autoantigenic targets such as the neutrophil PR3 will be discussed. GP2 IgA may represent a group of new pathogenic antibodies, which share characteristics of both type 2 and 3 of antibody-mediated hypersensitive reactions according to Coombs and Gell.

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“…Notably, these authors identified CUB/ zona pellucida-like domain-containing protein (CUZD1) as an autoantigenic target of type 2 PAB [41,45]. 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].…”

Section: Identification Of Crd-specific Pancreatic Autoantigensmentioning

confidence: 99%

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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CUZD1 and Anti-CUZD1 Antibodies as Markers of Cancer and Inflammatory Bowel Diseases

Cited by 16 publications

References 101 publications

Transient and Prolonged Response of Chicken Cecum Mucosa to Colonization with Different Gut Microbiota

Transient and Prolonged Response of Chicken Cecum Mucosa to Colonization with Different Gut Microbiota

The search for the Holy Grail: autoantigenic targets in primary sclerosing cholangitis associated with disease phenotype and neoplasia

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

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