Renal pathology in systemic lupus erythematosus involves both autoantibody deposition and a cellular inflammatory response, both of which are mediated by effector CD4 T cells. MRLlpr mice spontaneously develop massive perivascular infiltrates, but the pathways that regulate the development, trafficking, and effector functions of kidney-infiltrating T cells are poorly defined. To address these questions, we first surveyed inflammatory chemokine protein levels in nephritic kidneys from lupus-prone MRLlpr mice. After identifying highly elevated levels of the CXCR3 ligand CXCL9, we found that kidney-infiltrating effectors are enriched for expression of CXCR3, as well as P-selectin ligand and ICOS. Using genetic ablation, we demonstrate that ICOS plays an essential role in the establishment of renal perivascular infiltrates, although a small number of infiltrating cells remain around the blood vessels. Interestingly, though IgG autoantibody production is substantially reduced in Icos−/− MRLlpr mice, the progression of immune complex glomerulonephritis is only modestly diminished and the production of inflammatory chemokines, such as CXCL9, remains high in the kidney. We find that Icos−/− effector cell numbers are only slightly reduced and these have normal expression of CXCR3 and P-selectin ligand with intact migration to CXCL9. However, they have impaired production of inflammatory cytokines and fail to show evidence of efficient proliferation in the kidney. Thus, while dispensable for acquisition of renal trafficking receptor expression, ICOS is strictly required for local inflammatory functions of autoreactive CD4 T cells in murine lupus.
Background: Intravitreal vascular endothelial growth factor (VEGF) inhibitors stabilize vision in a majority of patients with neovascular age-related macular degeneration (AMD) and can improve vision in almost 40% of patients. However, some individuals who respond to anti-VEGF treatment still lose vision due to the formation of geographic atrophy (GA). While optical coherence tomography is often the primary imaging modality used, fluorescein angiography (FA) can provide useful information on GA development after choroidal neovascularization (CNV) regression. Methods: A retrospective chart review was conducted to evaluate the changes seen on FA over a 47-month period for 3 patients with neovascular AMD treated with anti-VEGF inhibitors. Results: All 3 patients were initially noted to have subfoveal CNV due to AMD at baseline; they were followed up monthly and treated on an as needed basis for at least 47 months with intravitreal VEGF inhibitors. All subjects had regression of their CNV lesions after VEGF blockade. Two subjects developed foveal atrophy. Conclusions: This case series depicts the changes on FA seen over a 4-year period and shows that GA can occur with regression of CNV after treatment with VEGF inhibitors.
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