Parasites alter the pathological phenotype of lupus nephritis.

Lupus nephritis is one of the most serious complications of systemic lupus erythematosus and manifests with considerable phenotypic and histological heterogeneity. In particular, diffuse proliferative lupus nephritis (DPLN) and membranous lupus nephritis (MLN) represent morphologic forms that are polar opposites. DPLN is associated with autoimmune responses dominated by Th1 immune response associated with high levels of interferon (IFN)-γ. In contrast, a Th2 cytokine response is associated with the pathogenesis of MLN. MRL/lpr mice develop human LN-like immune complex-associated nephritis and provide a suitable histological model for human DPLN. Infection with Schistosoma mansoni skewed a Th2-type immune response induction and IL-10 in MRL/lpr mice, drastically changing the pathophysiology of glomerulonephritis from DPLN to MLN accompanied by increased IgG1 and IgE in the sera. T cells in 32-week-old MRL/lpr mice infected with S. mansoni expressed significantly more IL-4 and IL-10 than T cells of uninfected mice; T cells with IFN-γ were comparable between infected and uninfected MR/lpr mice. Thus, the helminthic infection modified the cytokine microenvironment and altered the pathological phenotype of autoimmune nephritis.

Malarial infection of female BWF1 lupus mice alters the redox state in kidney and liver tissues and confers protection against lupus nephritis.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by an imbalanced redox state and increased apoptosis. Tropical infections, particularly malaria, may confer protection against SLE. Oxidative stress is a hallmark of SLE. We have measured changes in the levels of nitric oxide (NO), hydrogen peroxide (H2O2), malondialdehyde (MDA), and reduced glutathione (GSH) in both kidney and liver tissues of female BWF1 lupus mice, an experimental model of SLE, after infection with either live or gamma-irradiated malaria. We observed a decrease in NO, H2O2, and MDA levels in kidney tissues after infection of lupus mice with live malaria. Similarly, the levels of NO and H2O2 were significantly decreased in the liver tissues of lupus mice after infection with live malaria. Conversely, GSH levels were obviously increased in both kidney and liver tissues after infection of lupus mice with either live or gamma-irradiated malaria. Liver and kidney functions were significantly altered after infection of lupus mice with live malaria. We further investigated the ultrastructural changes and detected the number of apoptotic cells in kidney and liver tissues in situ by electron microscopy and TUNEL assays. Our data reveal that infection of lupus mice with malaria confers protection against lupus nephritis.

Acanthamoeba encephalitis in a patient with systemic lupus treated with rituximab.

Acanthamoeba species are free-living protozoa that can infect humans and animals. Acanthamoeba can cause serious central nervous system infections in immunocompromised hosts. Here we report a case of Acanthamoeba encephalitis in a patient with lupus nephritis, 1 month after completing a course of rituximab, an anti-CD20 chimeric antibody.

Toxoplasma gondii infection inhibits the development of lupus-like syndrome in autoimmune (New Zealand Black x New Zealand White) F1 mice.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of autoantibodies and lupus nephritis. In the present study using New Zealand Black (NZB) x New Zealand White (NZW) F1 (NZBW F1) mice, we planned to investigate the effects of Toxoplasma gondii infection on the progress of lupus nephritis. Female NZBW F1 mice at the age of 2 months were perorally infected with T. gondii. The T. gondii infection reduced the number of mice developing proteinuria and immune complex deposits in their kidneys and prolonged their life span. A marked decrease in the levels of IgM and IgG anti-DNA antibodies, especially IgG2a and IgG3 subclasses, was observed in T. gondii-infected NZBW F1 mice at 9 months of age. The level of anti-HSP70 IgG autoantibody in the sera of NZBW F1 mice was significantly higher than that in control mice at 9 weeks after T. gondii infection. Moreover, NZBW F1 mice treated with anti-self heat shock protein 70 (HSP70) monoclonal antibody were substantially protected against the onset of glomerulonephritis. Further, down-regulation of intracellular expression of IFN-gamma and IL-10 was shown in spleen cells of T. gondii-infected NZBW F1 mice. This was consistent with the previous data indicating the involvement of Th1-type and Th2-type cytokines in the development of lupus-like nephritis. These results suggest that T. gondii infection is capable of preventing the development of autoimmune renal disorder in NZBW F1 mice.