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Oncotarget. 2016 Sep 6;7(36):57593-57605. doi: 10.18632/oncotarget.11419.

Downregulation of the phosphatase JKAP/DUSP22 in T cells as a potential new biomarker of systemic lupus erythematosus nephritis.

Chuang HC1, Chen YM2,3,4, Hung WT2, Li JP1, Chen DY2,3,4, Lan JL5,6, Tan TH1,7,8.

Author information

1
Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan.
2
Division of Allergy, Immunology, and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.
3
Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
4
Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
5
School of Medicine, China Medical University Hospital, Taichung, Taiwan.
6
Division of Rheumatology and Immunology, China Medical University Hospital, Taichung, Taiwan.
7
Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan.
8
Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA.

Abstract

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is characterized by systemic inflammation and multiple organ failures. Dysregulation of T cells plays a critical role in SLE pathogenesis. Our previous study indicates that JKAP (also named DUSP22) inhibits T-cell activation and that JKAP knockout mice develop spontaneous autoimmunity; therefore, we investigated whether JKAP downregulation is involved in SLE patients. JKAP protein levels in purified T cells were examined by immunoblotting using blood samples from 43 SLE patients and 32 healthy controls. SLE patients showed significantly decreased JKAP protein levels in peripheral blood T cells compared to healthy controls. JKAP protein levels in peripheral blood T cells were inversely correlated with SLE disease activity index (SLEDAI) and anti-dsDNA antibody levels. JKAP downregulation in T cells was highly correlated with daily urinary protein amounts and with poor renal outcome in lupus nephritis patients. Notably, the diagnostic power of JKAP downregulation in T cells for active lupus nephritis was higher than those of serum anti-dsDNA antibody, C3, and C4 levels. Moreover, T-cell-specific transgenic mice expressing a dominant-negative JKAP mutant developed spontaneous autoimmune nephritis. Furthermore, JKAP-deficient T cells overproduced complement components, soluble ICAM-1, and soluble VCAM-1 in the kidney; these cytokines have been reported to be involved in lupus nephritis. Taken together, JKAP downregulation in T cells is a novel diagnostic and prognostic biomarker for SLE nephritis.

KEYWORDS:

DUSP22; Immune response; Immunity; Immunology and Microbiology Section; JKAP; SLE; T cells; nephritis

PMID:
27557500
PMCID:
PMC5295375
DOI:
10.18632/oncotarget.11419
[Indexed for MEDLINE]
Free PMC Article

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