Open AccessLupus nephritis: low urinary DNase I levels reflect loss of renal DNase I and may be utilized as a biomarker of disease progression
Author(s) -
Pedersen Hege L,
Horvei Kjersti D,
Thiyagarajan Dhivya,
Norby Gudrun E,
Seredkitalya,
Moroni Gabriella,
Eilertsen Gro Ø,
Holdaas Hallvard,
Strøm Erik H,
Bakland Gunnstein,
Meroni PierLuigi,
Rekvig Ole P
Publication year - 2018
Publication title -
the journal of pathology: clinical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.849
H-Index - 21
ISSN - 2056-4538
DOI - 10.1002/cjp2.99
Subject(s) - lupus nephritis , urinary system , pathology , biology , deoxyribonuclease i , nephritis , microbiology and biotechnology , immunology , medicine , endocrinology , disease , gene , biochemistry , base sequence
Renal DNase I is lost in advanced stages of lupus nephritis. Here, we determined if loss of renal DNase I reflects a concurrent loss of urinary DNase I, and whether absence of urinary DNase I predicts disease progression. Mouse and human DNase I protein and DNase I endonuclease activity levels were determined by western blot, gel, and radial activity assays at different stages of the murine and human forms of the disease. Cellular localization of DNase I was analyzed by immunohistochemistry, immunofluorescence, confocal microscopy, and immunoelectron microscopy. We further compared DNase I levels in human native and transplanted kidneys to determine if the disease depended on autologous renal genes, or whether the nephritic process proceeded also in transplanted kidneys. The data indicate that reduced renal DNase I expression level relates to serious progression of lupus nephritis in murine, human native, and transplanted kidneys. Notably, silencing of renal DNase I correlated with loss of DNase I endonuclease activity in the urine samples. Thus, urinary DNase I levels may therefore be used as a marker of lupus nephritis disease progression and reduce the need for renal biopsies.