TY - JOUR
T1 - Immunoglobulin G4+ B-cell receptor clones distinguish immunoglobulin G 4-related disease from primary sclerosing cholangitis and biliary/pancreatic malignancies
AU - Doorenspleet, Marieke E.
AU - Hubers, Lowiek M.
AU - Culver, Emma L.
AU - Maillette de Buy Wenniger, Lucas J.
AU - Klarenbeek, Paul L.
AU - Chapman, Roger W.
AU - Baas, Frank
AU - van de Graaf, Stan F.
AU - Verheij, Joanne
AU - van Gulik, Thomas M.
AU - Barnes, Eleanor
AU - Beuers, Ulrich
AU - de Vries, Niek
N1 - Funding Information: The excellent technical support by Rebecca E. Esveldt is gratefully acknowledged. We express our gratitude to Erik A.J. Rauws, Cyriel Y. Ponsioen, Martin H. Houben, Frans van der Heide, Henk-Marijn J. De Jonge, A. Boudewijn de Vries, Alaa Alkhalaf, and Marianne J. van Heerde who kindly referred patients for this study. This work was carried out on the Dutch national e-infrastructure with the support of SURF Foundation. Publisher Copyright: © 2016 The Authors. HEPATOLOGY published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) of the biliary tree and pancreas is difficult to distinguish from sclerosing cholangitis and biliary/pancreatic malignancies (CA). An accurate noninvasive test for diagnosis and monitoring of disease activity is lacking. We demonstrate that dominant IgG4+ B-cell receptor (BCR) clones determined by next-generation sequencing accurately distinguish patients with IgG4-associated cholangitis/autoimmune pancreatitis (n = 34) from those with primary sclerosing cholangitis (n = 17) and CA (n = 17). A novel, more affordable, and widely applicable quantitative polymerase chain reaction (qPCR) protocol analyzing the IgG4/IgG RNA ratio in blood also achieves excellent diagnostic accuracy (n = 125). Moreover, this qPCR test performed better than serum IgG4 levels in sensitivity (94% vs. 86%) and specificity (99% vs. 73%) and correlates with treatment response (n = 20). Conclusions: IgG4+ BCR clones and IgG4/IgG RNA ratio markedly improve delineation, early diagnosis, and monitoring of IgG4-RD of the biliary tree and pancreas. (Hepatology 2016;64:501-507).
AB - Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) of the biliary tree and pancreas is difficult to distinguish from sclerosing cholangitis and biliary/pancreatic malignancies (CA). An accurate noninvasive test for diagnosis and monitoring of disease activity is lacking. We demonstrate that dominant IgG4+ B-cell receptor (BCR) clones determined by next-generation sequencing accurately distinguish patients with IgG4-associated cholangitis/autoimmune pancreatitis (n = 34) from those with primary sclerosing cholangitis (n = 17) and CA (n = 17). A novel, more affordable, and widely applicable quantitative polymerase chain reaction (qPCR) protocol analyzing the IgG4/IgG RNA ratio in blood also achieves excellent diagnostic accuracy (n = 125). Moreover, this qPCR test performed better than serum IgG4 levels in sensitivity (94% vs. 86%) and specificity (99% vs. 73%) and correlates with treatment response (n = 20). Conclusions: IgG4+ BCR clones and IgG4/IgG RNA ratio markedly improve delineation, early diagnosis, and monitoring of IgG4-RD of the biliary tree and pancreas. (Hepatology 2016;64:501-507).
UR - http://www.scopus.com/inward/record.url?scp=84978977423&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/hep.28568
DO - https://doi.org/10.1002/hep.28568
M3 - Article
C2 - 27015613
SN - 0270-9139
VL - 64
SP - 501
EP - 507
JO - Hepatology
JF - Hepatology
IS - 2
ER -