Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Systematic lupus erythematosus (SLE) is a multisystem chronic inflammatory disease characterized by circulating antinuclear autoantibodies and dysfunction of B cells, T cells, and dendritic cells. Polymorphism of the HRES-1/RAB4 genomic locus has been associated with disease manifestations, such as nephritis, in SLE patients (Arthritis Rheum. 58:532-520), and its Rab4A gene product is overexpressed in T cells of SLE patients and in mice prior to disease onset and, remarkably, inhibition of Rab geranylgeranyl transferase prevented antinuclear antibody (ANA) production and nephritis in lupus-prone mice (Ann. Rheum. Dis. 73:1887-1897). To determine the role of Rab4a in lupus pathogenesis, its impact on ANA production and nephritis was investigated in Rab4A-KOCD4Cre (Rab4AKO) mice lacking expression of Rab4A in T cells relative to wild-type (WT) and floxed Rab4AQ72L knock-in (Rab4AQ72L) controls.
Methods: Four WT, three Rab4AQ72L and four Rab4AKO female mice matched for age were injected intraperitoneally with 0.5 ml per 20 g of body weight of pristane. 14 days after injection, ANA levels were measured in sera by ELISA and immunoglobulin G (IgG) and M (IgM) and complement 3 (C3) deposition as well as infiltration by CD11b+ macrophages, CD11c+ dendritic cells, CD138+ plasma cells, and CD3+ T cells were assessed by immunofluorescence using confocal microscopy. Statistical analyses were performed by t-test; two-tailed p<0.05 was considered significant.
Results: ANA levels were increased in Rab4AKO relative to Rab4AQ72L controls. Deposition of IgG and IgM was increased 2-fold, and C3 deposition was increased 4-fold in glomeruli of Rab4AKO relative to WT and Rab4AQ72L controls. Further, T cells (12-fold), plasma cells (2-fold), and macrophages (7-fold), but not dendritic cels, were accumulated in glomeruli and tubular interstitium of Rab4AKO mice relative to WT and Rab4AQ72L controls.
Conclusion: Based on these results, Rab4A protects against ANA production and nephritis in the pristane-induced model of SLE.
To cite this abstract in AMA style:Choudhary G, Huang N, Winans T, Kelly R, Blair S, Beckford M, Perl A. RAB4A Protects from Antinuclear Antibody Production and Nephritis in the Pristane-Induced Model of SLE [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/rab4a-protects-from-antinuclear-antibody-production-and-nephritis-in-the-pristane-induced-model-of-sle/. Accessed September 22, 2023.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rab4a-protects-from-antinuclear-antibody-production-and-nephritis-in-the-pristane-induced-model-of-sle/