Fate of Immune Complexes, Glomerulonephritis, and Cell-Mediated Vasculitis in Lupus-Prone MRL/Mp lpr/lpr Mice

Cruse, Julius M.; Lewis, Robert E.; Dilioglou, Smaroula

doi:10.1006/exmp.2000.2330

Cited by 10 publications

(4 citation statements)

References 35 publications

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“…In other studies, a lack of correlation between levels of anti-DNA autoantibodies and renal damage͞ survival of MRL͞Mp lpr mice has been observed (42). It has been reported that lpr mice are impaired in the capacity of resolving immune complex deposits in the kidney (43). Thus the vaccination-induced decrease in renal immune complexes may be caused by restoration of effective clearance, rather than reduction of deposition.…”

Section: Discussionmentioning

confidence: 95%

IL-18 cDNA vaccination protects mice from spontaneous lupus-like autoimmune disease

Bossù

Neumann

Giudice

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

111

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The lupus-like autoimmune syndrome of MRL͞Mp-Tnfrsf6 lpr (lpr) mice is characterized by progressive lymphadenopathy and autoantibody production, leading to early death from renal failure. Activation of T helper lymphocytes is one of the events in the pathogenesis of the disease in these mice and likely in human systemic lupus erythematosus. Among T helper lymphocytedependent cytokines, IFN-␥ plays a pivotal role in the abnormal cell activation and the fatal development of the lpr disease. IL-18, an inducer of IFN-␥ in T lymphocytes and natural killer cells, may contribute to the disease because cells from lpr mice are hypersensitive to IL-18 and express high levels of IL-18. To assess the contribution of IL-18 to the pathogenesis in the animal model, in vivo inhibition of IL-18 was attempted. Young lpr mice were vaccinated against autologous IL-18 by repeated administration of a cDNA coding for the murine IL-18 precursor. Vaccinated mice produced autoantibodies to murine IL-18 and exhibited a significant reduction in spontaneous lymphoproliferation and IFN-␥ production as well as less glomerulonephritis and renal damage. Moreover, mortality was significantly delayed in anti-IL-18-vaccinated mice. These studies support the concept that IL-18 plays a major role in the pathogenesis of the autoimmune syndrome of lpr mice and that a reduction in IL-18 activity could be a therapeutic strategy in autoimmune diseases.

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Section: Discussionmentioning

confidence: 95%

IL-18 cDNA vaccination protects mice from spontaneous lupus-like autoimmune disease

Bossù

Neumann

Giudice

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

111

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“…The typical pathological feature of SLE is systemic vasculitis with immune complex deposition [11]. It is rational to propose that some autoantibodies may be associated with specific clinical features of SLE.…”

Section: Discussionmentioning

confidence: 99%

Chinese SLE Treatment and Research Group Registry: III. Association of Autoantibodies with Clinical Manifestations in Chinese Patients with Systemic Lupus Erythematosus

Leng

et al. 2014

Journal of Immunology Research

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We investigated the characteristics of Chinese SLE patients by analyzing the association between specific autoantibodies and clinical manifestations of 2104 SLE patients from registry data of CSTAR cohort. Significant (P < 0.05) associations were found between anti-Sm antibody, anti-rRNP antibody, and malar rash; between anti-RNP antibody, anti-SSA antibody, and pulmonary arterial hypertension (PAH); between anti-SSB antibody and hematologic involvement; and between anti-dsDNA antibody and nephropathy. APL antibody was associated with hematologic involvement, interstitial lung disease, and a lower prevalence of oral ulcerations (P < 0.05). Associations were also found between anti-dsDNA antibody and a lower prevalence of photosensitivity, and between anti-SSA antibody and a lower prevalence of nephropathy (P < 0.05). Most of these findings were consistent with other studies in the literature but this study is the first report on the association between anti-SSA and a lower prevalence of nephropathy. The correlations of specific autoantibodies and clinical manifestations could provide clues for physicians to predict organ damages in SLE patients. We suggest that a thorough screening of autoantibodies should be carried out when the diagnosis of SLE is established, and repeated echocardiography annually in SLE patients with anti-RNP or anti-SSA antibody should be performed.

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“…There is experimental evidence showing resolution of glomerular immune complexes following cessation of antigenic stimulation [13, 14]. However, in clinical practice, repeat biopsies of the native kidney to look for resolution of glomerular deposits in immune complex glomerulonephritides are rarely performed (except for lupus flares), and patients are usually followed with clinical and laboratory parameters.…”

Section: Discussionmentioning

confidence: 99%

Complete biopsy-proven resolution of deposits in recurrent proliferative glomerulonephritis with monoclonal IgG deposits (PGNMIGD) following rituximab treatment in renal allograft

et al. 2019

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Background Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMIGD) is a disease entity classified under the group of “Monoclonal gammopathy-related kidney diseases”, and can recur after transplant. Clinical remission of proteinuria in patients with PGNMIGD has been previously shown following anti-B cell and/or anti-plasma cell therapies. Our case is the first to show complete histologic resolution of the glomerular monoclonal IgG kappa deposits in a case of recurrent PGNMIGD in renal allograft after rituximab and steroid treatment. This is a novel finding and it shows that the deposits are amenable to therapy. This case also highlights the importance of IgG subclass staining in the recognition of the monoclonal nature of the deposits. It is particularly important in PGNMIGD because only 20 to 30% of patients with this disease are reported to have detectable monoclonal gammopathy, and the deposits do not have any organized substructure on electron microscopic examination. Morphologically, they resemble polyclonal immune-type deposits seen in other immune complex glomerulonephritides such as lupus nephritis, infection-associated glomerulonephritis, and membranoproliferative glomerulonephritis (MPGN type I). Case presentation The patient is a 44 year old Caucasian male who received a living unrelated donor kidney transplant for end-stage renal disease diagnosed 7 years before transplant. The reported native kidney biopsy diagnosis was membranoproliferative glomerulonephritis (MPGN) with IgG, C3 and kappa restricted deposits. Fourteen months post-transplant, he presented with abrupt worsening of graft function, proteinuria and serum IgG kappa monoclonal spike. Allograft biopsy was consistent with recurrent PGNMIGD, considering the native kidney diagnosis and interval post-transplant. He underwent plasmapheresis, IV pooled immune globulin, steroid pulse and taper, and anti-CD-20 Rituximab therapy. Patient had gradual decline in proteinuria and complete resolution of the immune deposits on repeat biopsy 3 months later. Unfortunately he subsequently developed chronic antibody-mediated rejection and transplant glomerulopathy and graft failure 34 months post-transplant. Conclusions In a transplant setting, repeat allograft biopsies are frequently performed for graft dysfunction. This provides a good opportunity to study the evolution of the immune deposits following treatment. Our case shows complete histologic resolution of the deposits in allograft PGNMIGD.

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Fate of Immune Complexes, Glomerulonephritis, and Cell-Mediated Vasculitis in Lupus-Prone MRL/Mp lpr/lpr Mice

Cited by 10 publications

References 35 publications

IL-18 cDNA vaccination protects mice from spontaneous lupus-like autoimmune disease

IL-18 cDNA vaccination protects mice from spontaneous lupus-like autoimmune disease

Chinese SLE Treatment and Research Group Registry: III. Association of Autoantibodies with Clinical Manifestations in Chinese Patients with Systemic Lupus Erythematosus

Complete biopsy-proven resolution of deposits in recurrent proliferative glomerulonephritis with monoclonal IgG deposits (PGNMIGD) following rituximab treatment in renal allograft

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