OBJECTIVE: The significance of distinct B cell abnormalities in primary Sjögren's syndrome (SS) remains to be established. We undertook this study to analyze the phenotype and messenger RNA (mRNA) transcript profiles of B cell subsets in patients with primary SS and to compare them with those in sicca syndrome patients and healthy controls. METHODS: CD19+ B cells from 26 patients with primary SS, 27 sicca syndrome patients, and 22 healthy controls were analyzed by flow cytometry. Gene expression profiles of purified B cell subsets (from 3-5 subjects per group per test) were analyzed using Affymetrix gene arrays. RESULTS: Patients with primary SS had lower frequencies of CD27+IgD- switched memory B cells and CD27+IgD+ unswitched memory B cells compared with healthy controls. Unswitched memory B cell frequencies were also lower in sicca syndrome patients and correlated inversely with serologic hyperactivity in both disease states. Further, unswitched memory B cells in primary SS had lower expression of CD1c and CD21. Gene expression analysis of CD27+ memory B cells separated patients with primary SS from healthy controls and identified a subgroup of sicca syndrome patients with a primary SS-like transcript profile. Moreover, unswitched memory B cell gene expression analysis identified 187 genes differentially expressed between patients with primary SS and healthy controls. CONCLUSION: A decrease in unswitched memory B cells with serologic hyperactivity is characteristic of both established primary SS and a subgroup of sicca syndrome, which suggests the value of these B cells both as biomarkers of future disease progression and for understanding disease pathogenesis. Overall, the mRNA transcript analysis of unswitched memory B cells suggests that their activation in primary SS takes place through innate immune pathways in the context of attenuated antigen-mediated adaptive signaling. Thus, our findings provide important insight into the mechanisms and potential consequences of decreased unswitched memory B cells in primary SS.
OBJECTIVE: The significance of distinct B cell abnormalities in primary Sjögren's syndrome (SS) remains to be established. We undertook this study to analyze the phenotype and messenger RNA (mRNA) transcript profiles of B cell subsets in patients with primary SS and to compare them with those in sicca syndromepatients and healthy controls. METHODS:CD19+ B cells from 26 patients with primary SS, 27 sicca syndromepatients, and 22 healthy controls were analyzed by flow cytometry. Gene expression profiles of purified B cell subsets (from 3-5 subjects per group per test) were analyzed using Affymetrix gene arrays. RESULTS:Patients with primary SS had lower frequencies of CD27+IgD- switched memory B cells and CD27+IgD+ unswitched memory B cells compared with healthy controls. Unswitched memory B cell frequencies were also lower in sicca syndromepatients and correlated inversely with serologic hyperactivity in both disease states. Further, unswitched memory B cells in primary SS had lower expression of CD1c and CD21. Gene expression analysis of CD27+ memory B cells separated patients with primary SS from healthy controls and identified a subgroup of sicca syndromepatients with a primary SS-like transcript profile. Moreover, unswitched memory B cell gene expression analysis identified 187 genes differentially expressed between patients with primary SS and healthy controls. CONCLUSION: A decrease in unswitched memory B cells with serologic hyperactivity is characteristic of both established primary SS and a subgroup of sicca syndrome, which suggests the value of these B cells both as biomarkers of future disease progression and for understanding disease pathogenesis. Overall, the mRNA transcript analysis of unswitched memory B cells suggests that their activation in primary SS takes place through innate immune pathways in the context of attenuated antigen-mediated adaptive signaling. Thus, our findings provide important insight into the mechanisms and potential consequences of decreased unswitched memory B cells in primary SS.
Authors: Lenka L Allan; Annelein M Stax; Dong-Jun Zheng; Brian K Chung; Fred K Kozak; Rusung Tan; Peter van den Elzen Journal: J Immunol Date: 2011-03-30 Impact factor: 5.422
Authors: Yohei Iwata; Takashi Matsushita; Mayuka Horikawa; David J Dilillo; Koichi Yanaba; Guglielmo M Venturi; Paul M Szabolcs; Steven H Bernstein; Cynthia M Magro; Armistead D Williams; Russell P Hall; E William St Clair; Thomas F Tedder Journal: Blood Date: 2010-10-20 Impact factor: 22.113
Authors: Lisa S Westerberg; Carin Dahlberg; Marisa Baptista; Christopher J Moran; Cynthia Detre; Marton Keszei; Michelle A Eston; Frederick W Alt; Cox Terhorst; Luigi D Notarangelo; Scott B Snapper Journal: Blood Date: 2012-03-12 Impact factor: 22.113
Authors: Demin Li; An Hong; Qiong Lu; George F Gao; Boquan Jin; Gavin R Screaton; Xiao-Ning Xu Journal: Int Immunol Date: 2012-08-11 Impact factor: 4.823
Authors: Guillermo Carvajal Alegria; Pierre Gazeau; Sophie Hillion; Claire I Daïen; Divi Y K Cornec Journal: Clin Rev Allergy Immunol Date: 2017-10 Impact factor: 8.667
Authors: Arjun Sharma; Jeremy Kiripolsky; Ekaterina Klimatcheva; Alan Howell; Farzad Fereidouni; Richard Levenson; Thomas L Rothstein; Jill M Kramer Journal: Clin Immunol Date: 2016-01-28 Impact factor: 3.969
Authors: Scott A Jenks; Chungwen Wei; Regina Bugrovsky; Aisha Hill; Xiaoqian Wang; Francesca M Rossi; Kevin Cashman; Matthew C Woodruff; Laura D Aspey; S Sam Lim; Gaobin Bao; Cristina Drenkard; Ignacio Sanz Journal: Ann Rheum Dis Date: 2021-06-03 Impact factor: 27.973
Authors: E William St Clair; Alan N Baer; Chungwen Wei; Ghaith Noaiseh; Anne Parke; Andreea Coca; Tammy O Utset; Mark C Genovese; Daniel J Wallace; James McNamara; Karen Boyle; Lynette Keyes-Elstein; Jeffrey L Browning; Nathalie Franchimont; Kira Smith; Joel M Guthridge; Ignacio Sanz; Judith A James Journal: Arthritis Rheumatol Date: 2018-07-18 Impact factor: 15.483