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

// Huai-Chia Chuang 1,* , Yi-Ming Chen 2,3,4,* , Wei-Ting Hung 2 , Ju-Pi Li 1 , Der-Yuan Chen 2,3,4 , Joung-Liang Lan 5,6 and Tse-Hua Tan 1,7,8 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 * These authors have contributed equally to this work Correspondence to: Tse-Hua Tan, email: // Joung-Liang Lan, email: // Der-Yuan Chen, email: // Keywords : JKAP, DUSP22, SLE, nephritis, T cells, Immunology and Microbiology Section, Immune response, Immunity Received : March 04, 2016 Accepted : August 13, 2016 Published : August 19, 2016 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.