Complement Deficiencies Result in Surrogate Pathways of Complement Activation in Novel Polygenic Lupus-like Models of Kidney Injury.

ABSTRACT: Lupus nephritis (LN) is a major contributor to morbidity and mortality in lupus patients, but the mechanisms of kidney damage remain unclear. In this study, we introduce, to our knowledge, novel models of LN designed to resemble the polygenic nature of human lupus by embodying three key genetic alterations: the Sle1 interval leading to anti-chromatin autoantibodies; Mfge8^-/- , leading to defective clearance of apoptotic cells; and either C1q^-/- or C3^-/- , leading to low complement levels. We report that proliferative glomerulonephritis arose only in the presence of all three abnormalities (i.e., in Sle1.Mfge8 ^-/- C1q ^-/- and Sle1.Mfge8 ^-/- C3 ^-/- triple-mutan

SUBMITTER: Skopelja-Gardner S 

PROVIDER: S-EPMC7365257 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature