IgM-linked SerpinB3 and SerpinB4 in Sera of Patients with Chronic Liver Disease

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Jul 19

PMID 22808225

Citations 8

Authors

Alessandra Biasiolo

Natascia Tono

Mariagrazia Ruvoletto

Santina Quarta

Cristian Turato

Gianmarco Villano

Luca Beneduce

Giorgio Fassina

Carlo Merkel

Angelo Gatta

Patrizia Pontisso

Affiliations

Soon will be listed here.

Abstract

Background: Epidemiological studies indicate that a growing number of cirrhotic patients will develop hepatocellular carcinoma (HCC) in the next decade. Recent findings have demonstrated that Squamous cell carcinoma antigen 1 (SCCA1) and 2 (SCCA2) isoforms, now classified as serpinB3 and serpinB4, are over-expressed in HCC, but not in normal liver. As reported, high levels of circulating SCCA-IgM immunocomplexes in patients with cirrhosis are significantly associated with HCC development.

Aim: To ascertain whether IgM-linked SCCA isoforms circulate in patients with chronic liver disease, compared to total SCCA-IgM levels.

Methodology And Findings: 79 patients with chronic liver disease were studied, including 17 patients with chronic hepatitis, 36 patients with cirrhosis and 26 with HCC. 28 blood donors were used as control. Monoclonal antibodies against serpinB3 and serpinB4 were used as catcher antibodies to set up specific ELISA assays, while total SCCA-IgM immunocomplexes were detected by commercially available ELISA assay. Overall, the results revealed a better diagnostic sensitivity of total SCCA-IgM assay, compared to both serpinB3 and serpinB4 IgM-linked assays. SerpinB4-IgM median values obtained with SCC103 antibody were moderately higher in patients with cirrhosis than in those with HCC, median values: 0.168 (IQR 0.140-0.427) vs. 0.140 (IQR 0.140-0.278), (p = 0.177). A trend toward decreasing serpinB4-IgM/serpinB3-IgM median ratio was observed in patients with advanced liver disease, being 1.08 in patients with HCC, 1.10 in patients with cirrhosis and 1.40 in patients with chronic hepatitis (p = 0.079).

Conclusions: IgM-linked SCCA isoforms in serum of patients with chronic liver diseases were quantified for the first time. Although the number of patients was limited, this preliminary study reveals that the relative balance of the two serpin isoforms is altered in HCC and it is characterized by a lower serpinB4-IgM/serpinB3-IgM ratio, determined by lower serpinB4 levels.

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References

Pontisso P, Quarta S, Caberlotto C, Beneduce L, Marino M, Bernardinello E . Progressive increase of SCCA-IgM immune complexes in cirrhotic patients is associated with development of hepatocellular carcinoma. Int J Cancer. 2006; 119(4):735-40. DOI: 10.1002/ijc.21908. View

Vollmers H, Brandlein S . Natural antibodies and cancer. J Autoimmun. 2007; 29(4):295-302. DOI: 10.1016/j.jaut.2007.07.013. View

Sakata Y, Arima K, Takeshita K, Takai T, Aoki S, Ogawa H . Characterization of novel squamous cell carcinoma antigen-related molecules in mice. Biochem Biophys Res Commun. 2004; 324(4):1340-5. DOI: 10.1016/j.bbrc.2004.09.204. View

Giannelli G, Marinosci F, Sgarra C, Lupo L, Dentico P, Antonaci S . Clinical role of tissue and serum levels of SCCA antigen in hepatocellular carcinoma. Int J Cancer. 2005; 116(4):579-83. DOI: 10.1002/ijc.20847. View

Beneduce L, Castaldi F, Marino M, Tono N, Gatta A, Pontisso P . Improvement of liver cancer detection with simultaneous assessment of circulating levels of free alpha-fetoprotein (AFP) and AFP-IgM complexes. Int J Biol Markers. 2004; 19(2):155-9. DOI: 10.1177/172460080401900211. View

Suminami Y, Nawata S, Kato H . Biological role of SCC antigen. Tumour Biol. 1998; 19(6):488-93. DOI: 10.1159/000030042. View

Cataltepe S, Gornstein E, Schick C, Kamachi Y, Chatson K, Fries J . Co-expression of the squamous cell carcinoma antigens 1 and 2 in normal adult human tissues and squamous cell carcinomas. J Histochem Cytochem. 2000; 48(1):113-22. DOI: 10.1177/002215540004800112. View

Takeda A, Kajiya A, Iwasawa A, Nakamura Y, Hibino T . Aberrant expression of serpin squamous cell carcinoma antigen 2 in human tumor tissues and cell lines: evidence of protection from tumor necrosis factor-mediated apoptosis. Biol Chem. 2002; 383(7-8):1231-6. DOI: 10.1515/BC.2002.136. View

Castaldi F, Marino M, Beneduce L, Belluco C, De Marchi F, Mammano E . Detection of circulating CEA-IgM complexes in early stage colorectal cancer. Int J Biol Markers. 2006; 20(4):204-8. DOI: 10.1177/172460080502000402. View

10.

Armbruster D, Pry T . Limit of blank, limit of detection and limit of quantitation. Clin Biochem Rev. 2008; 29 Suppl 1:S49-52. PMC: 2556583. View

11.

Biasiolo A, Chemello L, Quarta S, Cavalletto L, Bortolotti F, Caberlotto C . Monitoring SCCA-IgM complexes in serum predicts liver disease progression in patients with chronic hepatitis. J Viral Hepat. 2008; 15(4):246-9. DOI: 10.1111/j.1365-2893.2007.00935.x. View

12.

Stein P, Leslie A, Finch J, Turnell W, McLaughlin P, Carrell R . Crystal structure of ovalbumin as a model for the reactive centre of serpins. Nature. 1990; 347(6288):99-102. DOI: 10.1038/347099a0. View

13.

Vidalino L, Doria A, Quarta S, Zen M, Gatta A, Pontisso P . SERPINB3, apoptosis and autoimmunity. Autoimmun Rev. 2009; 9(2):108-12. DOI: 10.1016/j.autrev.2009.03.011. View

14.

Nustad K, Nilsson O, Majnesjo K, Murakami A, Sugino N, Warren D . Characterization of monoclonal antibodies directed against squamous cell carcinoma antigens: report of the second TD-10 workshop. Tumour Biol. 2009; 30(1):26-36. DOI: 10.1159/000199448. View

15.

Pak S, Kumar V, Tsu C, Luke C, Askew Y, Askew D . SRP-2 is a cross-class inhibitor that participates in postembryonic development of the nematode Caenorhabditis elegans: initial characterization of the clade L serpins. J Biol Chem. 2004; 279(15):15448-59. DOI: 10.1074/jbc.M400261200. View

16.

Bhardwaj N . Harnessing the immune system to treat cancer. J Clin Invest. 2007; 117(5):1130-6. PMC: 1857237. DOI: 10.1172/JCI32136. View

17.

Dunn G, Bruce A, Ikeda H, Old L, Schreiber R . Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002; 3(11):991-8. DOI: 10.1038/ni1102-991. View

18.

Torre G . SCC antigen in malignant and nonmalignant squamous lesions. Tumour Biol. 1998; 19(6):517-26. DOI: 10.1159/000030045. View

19.

Guido M, Roskams T, Pontisso P, Fassan M, Thung S, Giacomelli L . Squamous cell carcinoma antigen in human liver carcinogenesis. J Clin Pathol. 2007; 61(4):445-7. DOI: 10.1136/jcp.2007.051383. View

20.

Murakami A, Suminami Y, Sakaguchi Y, Nawata S, Numa F, Kishi F . Specific detection and quantitation of SCC antigen 1 and SCC antigen 2 mRNAs by fluorescence-based asymmetric semi-nested reverse transcription PCR. Tumour Biol. 2000; 21(4):224-34. DOI: 10.1159/000030128. View