AUTHOR=Alkharaan Hassan , Lu Liyan , Gabarrini Giorgio , Halimi Asif , Ateeb Zeeshan , Sobkowiak Michał J. , Davanian Haleh , Fernández Moro Carlos , Jansson Leif , Del Chiaro Marco , Özenci Volkan , Sällberg Chen Margaret 

TITLE=Circulating and Salivary Antibodies to Fusobacterium nucleatum Are Associated With Cystic Pancreatic Neoplasm Malignancy

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.02003

DOI=10.3389/fimmu.2020.02003

ISSN=1664-3224

ABSTRACT=<sec><title>Objectives</title><p>Intraductal papillary mucinous neoplasms (IPMNs) are cystic precursor lesions to pancreatic cancer. The presence of oral microbes in pancreatic tissue or cyst fluid has been associated with high-grade dysplasia (HGD) and cancer. The present study aims at investigating if humoral immunity to pancreas-associated oral microbes reflects IPMN severity.</p></sec><sec><title>Design</title><p>Paired plasma (<italic>n</italic> = 109) and saliva (<italic>n</italic> = 65) samples were obtained from IPMN pancreatic cystic tumor cases and controls, for anti-bacterial antibody analysis and DNA quantification by enzyme-linked immunosorbent assay (ELISA) and qPCR, respectively. Tumor severity was graded by histopathology, laboratory, and clinical data. Circulating plasma and salivary antibody reactivity to a pancreas-associated oral microbe panel were measured by ELISA and correlated to tumor severity.</p></sec><sec><title>Results</title><p>The patient group with high-risk cystic tumors (HGD and/or associated invasive cancer) shows ample circulating IgG reactivity to <italic>Fusobacterium nucleatum</italic> (<italic>F. nucleatum</italic>) but not to <italic>Granulicatella adiacens</italic> (<italic>G. adiacens</italic>), which is independent of the salivary bacteria DNA levels. This group also shows higher salivary IgA reactivity to <italic>F. nucleatum</italic>, Fap2 of <italic>F. nucleatum</italic>, and <italic>Streptococcus gordonii</italic> (<italic>S. gordonii</italic>) compared to low-risk IPMN and controls. The salivary antibody reactivity to <italic>F. nucleatum</italic> and Fap2 are found to be highly correlated, and cross-competition assays further confirm that these antibodies appear cross-reactive.</p></sec><sec><title>Conclusion</title><p>Our findings indicate that humoral reactivity against pancreas-associated oral microbes may reflect IPMN severity. These findings are beneficial for biomarker development.</p></sec>