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The Plasma Cell Signature in Autoimmune Disease
Author(s) -
Streicher Katie,
Morehouse Christopher A.,
Groves Christopher J.,
Rajan Bhargavi,
Pilataxi Fernanda,
Lehmann Kim P.,
Brohawn Philip Z.,
Higgs Brandon W.,
McKeever Kathleen,
Greenberg Steven A.,
Fiorentino David,
Richman Laura K.,
Jallal Bahija,
Herbst Ronald,
Yao Yihong,
Ranade Koustubh
Publication year - 2014
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.38194
Subject(s) - gene signature , autoantibody , rheumatoid arthritis , cd19 , microarray , autoimmune disease , immunology , microarray analysis techniques , ex vivo , medicine , flow cytometry , gene expression , gene , biology , in vivo , antibody , genetics
Objective Production of pathogenic autoantibodies by self‐reactive plasma cells (PCs) is a hallmark of autoimmune diseases. We undertook this study to investigate the prevalence of PCs and their relationship to known pathogenic pathways to increase our understanding of the role of PCs in disease progression and treatment response. Methods We developed a sensitive gene expression–based method to overcome the challenges of measuring PCs using flow cytometry. Whole‐genome microarray analysis of sorted cellular fractions identified a panel of genes, IGHA1, IGJ, IGKC, IGKV4‐1, and TNFRSF17, expressed predominantly in PCs. The sensitivity of the PC signature score created from the combined expression levels of these genes was assessed through ex vivo experiments with sorted cells. This PC gene expression signature was used for monitoring changes in PC levels following anti‐CD19 therapy, for evaluating the relationship between PCs and other autoimmune disease–related genes, and for estimating PC levels in affected blood and tissue from patients with multiple autoimmune diseases. Results The PC signature was highly sensitive and capable of detecting a change in as few as 360 PCs. The PC signature was reduced more than 90% in scleroderma patients following anti‐CD19 treatment, and this reduction was highly correlated (r = 0.80) with inhibition of collagen gene expression. Evaluation of multiple autoimmune diseases revealed that 30–35% of lupus and rheumatoid arthritis patients had increased levels of PCs. Conclusion This newly developed PC signature provides a robust and accurate method of measuring PC levels in the clinic. Our results highlight subsets of patients across multiple autoimmune diseases who may benefit from PC‐depleting therapy.