title: Downregulation of the phosphatase JKAP/DUSP22 in T cells as a potential new biomarker of systemic lupus erythematosus nephritis.
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.
authors.affiliation: Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Huai-Chia
authors.initials: HC
authors.lastname: Chuang
authors.affiliation: Division of Allergy, Immunology, and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.|Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.|Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Chen
authors.affiliation: Division of Allergy, Immunology, and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Hung
authors.affiliation: Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Ju-Pi
authors.initials: JP
authors.lastname: Li
authors.affiliation: Division of Allergy, Immunology, and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.|Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.|Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Der-Yuan
authors.initials: DY
authors.lastname: Chen
authors.affiliation: School of Medicine, China Medical University Hospital, Taichung, Taiwan.|Division of Rheumatology and Immunology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Joung-Liang
authors.initials: JL
authors.lastname: Lan
authors.affiliation: Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan.|Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan.|Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Tse-Hua
authors.initials: TH
authors.lastname: Tan
mesh_terms: D000328:Adult; D000818:Animals; D000906:Antibodies / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D015536:Down-Regulation; D054637:Dual-Specificity Phosphatases / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000175:diagnosis; D008181:Lupus Nephritis / Q000097:blood* / Q000175:diagnosis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000378:metabolism*; D015999:Multivariate Analysis; D011379:Prognosis; D013601:T-Lymphocytes / Q000166:cytology*; D055815:Young Adult
chemical_list: D000906:Antibodies; D015415:Biomarkers; D054639:Mitogen-Activated Protein Kinase Phosphatases; C442824:DUSP22 protein, human; D054637:Dual-Specificity Phosphatases
keywords: DUSP22; Immune response; Immunity; Immunology and Microbiology Section; JKAP; SLE; T cells; nephritis