Abstract
Calreticulin, upon translocation to the cell surface, plays a critical role in the recognition of tumour cells and in experimentally induced cellular anti-tumour immunity. However, less is known about anti-calreticulin antibodies and their role in malignancies.
Using enzyme-linked immunosorbent assay (ELISA), we found immunoglobulin (Ig)A and/or IgG anti-calreticulin antibodies in sera of approximately 63% of patients with hepatocellular carcinoma (HCC), 57% of patients with colorectal adenocarcinoma (CRA) and 47% of patients with pancreatic adenocarcinoma (PACA), while healthy controls, patients with viral hepatitis C and with chronic pancreatitis reached only 2%, 20% and 31% seropositivity, respectively. We found significantly elevated mean levels of IgA anti-calreticulin antibodies (P < 0 center dot 001) in patients with HCC (78 center dot 7 +/- 52 center dot 3 AU, mean +/- standard deviation), PACA (66 center dot 5 +/- 30 center dot 9 AU) and CRA (61 center dot 8 +/- 25 center dot 8 AU) when compared to healthy controls (41 center dot 4 +/- 19 center dot 2 AU).
Significantly elevated mean levels of IgG anti-calreticulin antibodies (P < 0 center dot 001) were detected in patients with HCC (121 center dot 9 +/- 94 center dot 2 AU), gall bladder adenocarcinoma (118 center dot 4 +/- 80 center dot 0 AU) and PACA (88 center dot 7 +/- 55 center dot 6 AU) when compared to healthy controls (56 center dot 7 +/- 22 center dot 9 AU). Pepscan analysis revealed a large number of antigenic epitopes of calreticulin recognized by both IgA and IgG antibodies of patients with HCC and PACA, indicating robust systemic immune response.
Moreover, significantly elevated levels of antibodies against peptide KGEWKPRQIDNP (P < 0 center dot 001) in these patients, tested by ELISA, confirmed the distinct character of antibody reactivity against calreticulin. The high occurrence and specificity of serum anti-calreticulin autoantibodies in the majority of patients with some gastrointestinal malignancies provide the evidence for their possible clinical relevance