Z Gastroenterol 2015; 53 - A4_41
DOI: 10.1055/s-0034-1397193

Progranulin autoantibodies and genetic variation in patients with cholangiocarcinoma

V Zimmer 1, L Thurner 2, M Acalovschi 3, M Pfreundschuh 2, F Lammert 1
  • 1Saarland University Hospital, Department of Medicine II, Homburg, Germany
  • 2Saarland University Hospital, Department of Medicine I, Homburg, Germany
  • 3University Iuliu Hatieganu, Department of Medicine III, Cluj-Napoca, Romania

Background: Recently, the novel growth factor and TNF signalling adaptor progranulin (PGRN) has been implicated in the inflammation-driven pathogenesis of cholangiocarcinoma (CCA).(1,2) Neutralizing PGRN autoantibodies have been described in autoimmune diseases, including inflammatory bowel disease (IBD).(3,4) Therefore, our aim now was to assess PGRN autoantibody incidence and potential effects of the common PGRN gene variant rs5848 (known to be associated with reduced PGRN serum concentrations) on susceptibility and PGRN autoantibody formation in a large European CCA population.(5)

Patients & Methods: Overall, 221 individuals with CCA (males n= 131, age 66 ± 11 years) originating from Germany (n= 164) and Romania (n= 57) and 295 CCA-free control individuals were genotyped. The common non-synonymous single nucleotide polymorphism (SNP) rs5846 was genotyped by PCR-based assays with 5'-nuclease and fluorescence detection (TaqMan). PGRN autoantibodies were determined by ELISA.(4)

Results: rs5848 genotype frequencies in the control group were consistent with the Hardy-Weinberg equilibrium (HWE), with a call rate > 99% indicating robust genotyping. The association tests did not provide evidence for genetic CCA risk modulation by the PGRN variant (Odds ratio= 0.92; 95% confidence interval= 0.71 – 1.19; P> 0.05). Seven of 61 patients (11.5%) tested positive for PGRN autoantibodies, with no significant sex differences (3/32 males, 4/29 females). Considering rs5848 variation in the subgroup with available PGRN autoantibody status, no significant differences in allele and genotype distribution were observed.

Conclusions: Our preliminary data indicate PGRN autoantibodies as a novel potential tumor antigen in a defined subset of CCA patients. Extension of the current study in larger sample sizes and delineation of potential implications in terms of CCA subtypes and prognostic relevance of PGRN autoimmunity is warranted.

References:

[1] Frampton et al. Gut 2012

[2] Frampton et al. Am J Physiol Gastrointest Liver Physiol 2012

[3] Thurner et al. J Autoimmun 2013

[4] Thurner et al. Dig Dis Sci 2014

[5] Hsiung et al. J Neurol Sci 2011

Corresponding author: Zimmer, Vincent

E-Mail: vincent.zimmer@uks.eu