CUB and zona pellucida-like domain-containing protein 1 (CUZD1) has been previously shown to be specifically expressed in normal pancreas and was proposed as a candidate biomarker for pancreatic related disorders. Due to the lack of specific reagents and techniques, its levels in tissues and biological fluids have not been extensively examined. We generated mouse monoclonal antibodies against recombinant CUZD1 and used them for the development of an enzyme-linked immunosorbent assay (ELISA). Analysis of various human extracts showed that CUZD1 is measured in high levels in pancreas and at much lower (but detectable) levels in several other tissues. Analysis of biological fluids showed that CUZD1 is detected exclusively in pancreatic juice.
CUZD1 has been previously linked to diseases (such as pancreatitis, ovarian cancer and IBD) but it is currently unknown if the expression levels of this antigen are elevated in any of the aforementioned or other disorders. Analysis of a large number of serum samples from patients with various malignant and benign disorders showed that CUZD1 levels were elevated in patients with ovarian cysts but not ovarian cancer.
CUZD1 is a pancreas-specific protein but it is unclear if its expression is elevated in malignant conditions of the pancreas. IHC staining of pancreatic ductal adenocarcinoma (PDAC) and acinar cell carcinoma (ACC) tissue sections revealed that CUZD1 protein was highly expressed in ACC but not in PDAC.
CUZD1 is one of the targets of pancreatic autoantibodies (PABs) which have been emerged as possible biomarkers for Inflammatory Bowel Disease (IBD). Data assessing the diagnostic significance of CUZD1 autoantibodies in patients with IBD are scarce, mainly due to the lack of high throughput techniques for their detection. We developed an ELISA targeting CUZD1 autoantibodies and used it to analyze 200 serum samples from IBD patients and 129 patients assessed for various autoimmune diseases (vADs). CUZD1 autoantibodies were detected in 16% of CrD patients in 9% of UC patients and in less than 5% of patients being tested for vADs.
In conclusion, this thesis encompasses the development and validation of analytical techniques targeting CUZD1 antigen and CUZD1 autoantibodies. These tools can facilitate future investigations aiming to delineate the role of CUZD1 in physiology and pathobiology.Ph.D
