AIMS: To explore whether immunoglobulin (Ig)G4-related sclerosing cholangitis (IgG4-SC) contributes to end-stage primary sclerosing cholangitis (PSC) in the United Kingdom. METHODS AND RESULTS: This study consisted of 41 patients who underwent liver transplantation for advanced PSC. Explanted livers were examined histologically with an emphasis on IgG4-positive plasma cell infiltration. Thirty-nine cases (95%) had minimal or mild infiltration of IgG4-positive plasma cells (≤ 30 cells/high-power field). In contrast, two cases (5%) showed plasma cell IgG4-positivity in more than 100 cells/high-power field. IgG4-positive plasma cells were accumulated preferentially in a (xantho)granulomatous tissue within large bile ducts. Except for the presence of IgG4-positive plasma cells, there was no significant histological difference between IgG4-positive and negative cases. Both showed sclerosing cholangitis with bile duct erosion and xanthogranulomatous reaction more in keeping with PSC than typical IgG4-SC. Clinically, the two patients differed from typical IgG4-related disease, in that both had associated ulcerative colitis, and one of them was younger than expected for IgG4-SC (28 years old). CONCLUSIONS: No classical IgG4-SC could be identified in patients explanted for PSC. The two cases identified with numerous IgG4-positive plasma cells suggest a superimposed immune mechanism of uncertain nature. A prospective study is needed to assess whether such cases will be steroid-sensitive.
AIMS: To explore whether immunoglobulin (Ig)G4-related sclerosing cholangitis (IgG4-SC) contributes to end-stage primary sclerosing cholangitis (PSC) in the United Kingdom. METHODS AND RESULTS: This study consisted of 41 patients who underwent liver transplantation for advanced PSC. Explanted livers were examined histologically with an emphasis on IgG4-positive plasma cell infiltration. Thirty-nine cases (95%) had minimal or mild infiltration of IgG4-positive plasma cells (≤ 30 cells/high-power field). In contrast, two cases (5%) showed plasma cell IgG4-positivity in more than 100 cells/high-power field. IgG4-positive plasma cells were accumulated preferentially in a (xantho)granulomatous tissue within large bile ducts. Except for the presence of IgG4-positive plasma cells, there was no significant histological difference between IgG4-positive and negative cases. Both showed sclerosing cholangitis with bile duct erosion and xanthogranulomatous reaction more in keeping with PSC than typical IgG4-SC. Clinically, the two patients differed from typical IgG4-related disease, in that both had associated ulcerative colitis, and one of them was younger than expected for IgG4-SC (28 years old). CONCLUSIONS: No classical IgG4-SC could be identified in patients explanted for PSC. The two cases identified with numerous IgG4-positive plasma cells suggest a superimposed immune mechanism of uncertain nature. A prospective study is needed to assess whether such cases will be steroid-sensitive.
Authors: Arzoo M Patel; Yuxin S Liu; Scott P Davies; Rachel M Brown; Deirdre A Kelly; Dagmar Scheel-Toellner; Gary M Reynolds; Zania Stamataki Journal: Front Immunol Date: 2021-09-23 Impact factor: 8.786
Authors: Hussein A Abbas; Dapeng Hao; Katarzyna Tomczak; Praveen Barrodia; Jin Seon Im; Patrick K Reville; Zoe Alaniz; Wei Wang; Ruiping Wang; Feng Wang; Gheath Al-Atrash; Koichi Takahashi; Jing Ning; Maomao Ding; Hannah C Beird; Jairo T Mathews; Latasha Little; Jianhua Zhang; Sreyashi Basu; Marina Konopleva; Mario L Marques-Piubelli; Luisa M Solis; Edwin Roger Parra; Wei Lu; Auriole Tamegnon; Guillermo Garcia-Manero; Michael R Green; Padmanee Sharma; James P Allison; Steven M Kornblau; Kunal Rai; Linghua Wang; Naval Daver; Andrew Futreal Journal: Nat Commun Date: 2021-10-18 Impact factor: 14.919