Interferon alpha on NZM2328.Lc1R27: Enhancing autoimmunity and immune complex-mediated glomerulonephritis without end stage renal failure

被引：22

作者：

Dai, Chao ^{[1
]}

Wang, Hongyang ^{[1
]}

Sung, Sun-Sang J. ^{[1
]}

Sharma, Rahul ^{[1
]}

Kannapell, Carol ^{[1
]}

Han, Wei ^{[1
]}

Wang, Qian ^{[1
]}

Davidson, Anne ^{[2
]}

Gaskin, Felicia ^{[3
]}

Fu, Shu Man ^{[1
,4
,5
]}

机构：

[1] Univ Virginia, Dept Med, Ctr Immun Inflammat & Regenerat Med, Charlottesville, VA USA

[2] Feinstein Inst Med Res, Ctr Autoimmun & Musculoskeletal Dis, Manhasset, NY USA

[3] Univ Virginia, Sch Med, Dept Psychiat & Neurobehav Sci, Charlottesville, VA 22908 USA

[4] Univ Virginia, Dept Med, Div Rheumatol, Charlottesville, VA USA

[5] Univ Virginia, Sch Med, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA 22908 USA

来源：

CLINICAL IMMUNOLOGY | 2014年 / 154卷 / 01期

关键词：

SLE; Interferon alpha; Mouse model for lupus nephritis; SYSTEMIC-LUPUS-ERYTHEMATOSUS; DISEASE; MANIFESTATIONS; EXPRESSION; SIGNATURE; BLOOD;

D O I：

10.1016/j.clim.2014.06.008

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Interferon alpha (IFN alpha) may play a significant role in systemic lupus erythematosus (SLE) pathogenesis. Recent literature suggests that IFN alpha does not correlate with disease activities and blockade of IFN alpha is not effective in treating SLE. This study aims to delineate further the role of IFN alpha in SLE. 12-week old NZM2328 and its congenic NZM2328.Lc1R27 (R27) female mice were challenged with adenovirus-IFN alpha (adeno-IFN alpha) or adenovirus-LacZ (adeno-LacZ). Only adeno-IFN alpha treated NZM2328 developed severe proteinuria and died of chronic glomerulonephritis (GN) and end stage renal disease. Adeno-IFN alpha treated R27 did develop immune complex-mediated GN but had normal renal function. Adeno-LacZ treated NZM2328 showed enlarged glomeruli and increased cellularity without immune complex deposition. Adeno-LacZ treated R27 did not show serological and histological abnormalities. Adeno-IFN alpha induced anti-dsDNA and anti-kidney autoantibodies in NZM2328 and R27. These results suggest that end organ damage is host-dependent and less related to autoimmunity and may have significant implications in SLE pathogenesis. (C) 2014 Published by Elsevier Inc.

引用

页码：66 / 71

页数：6

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