Double negative T cells, a potential biomarker for systemic lupus erythematosus

Jessy J Alexander; Alexander Jacob; Anthony Chang; Richard J Quigg; James N Jarvis

doi:10.1093/pcmedi/pbaa001

Double negative T cells, a potential biomarker for systemic lupus erythematosus

Precis Clin Med. 2020 Mar;3(1):34-43. doi: 10.1093/pcmedi/pbaa001. Epub 2020 Jan 20.

Authors

Jessy J Alexander^{1

2}, Alexander Jacob^{1

2}, Anthony Chang², Richard J Quigg^{1

2}, James N Jarvis¹

Affiliations

¹ Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
² Departments of Medicine, Pediatrics, Jacobs School of Medicine and Biomedical Sciences and Genetics, Genomics, & Bioinformatics Program, University at Buffalo, Buffalo, NY 14203, USA.

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease that is a challenge to diagnose and treat. There is an urgent need for biomarkers to help define organ involvement, and more effective therapies. A unique population of T cells, the CD3⁺CD4^-CD8^- (DNeg) cells, is significantly increased in lupus patients. Twenty-seven cases (53%) of pediatric SLE patients had elevated DNeg cells in their peripheral blood, which correlated with kidney function (R² = 0.54). Significant infiltration of DNeg cells was observed in both adult and pediatric lupus kidneys by immunofluorescence. For the first time, this study provides direct evidence that DNeg cells facilitate kidney injury in preclinical 8-week-old MRL/lpr lupus mice. In lupus mice, the increase in DNeg cells tracked with worsening disease and correlated with kidney function (R² = 0.85). Our results show that DNeg cells per se can cause kidney dysfunction, increase in number with increase in disease pathology, and could serve as a potential biomarker.

Keywords: CD3+CD4−CD8− T cells; glomerulonephritis; inflammation; lupus.

Grants and funding

R01 DK111222/DK/NIDDK NIH HHS/United States