The Pathogenesis, Diagnosis and Treatment of Lupus Nephritis
Purpose of Review. Renal involvement is a major cause of morbidity and mortality in systemic lupus erythematosus. In this review, we provide an update on recent discoveries in the pathogenesis, diagnosis, and treatment of lupus nephritis.
Recent Findings. Localized long-lived plasma cells have been identified as playing an important role in lupus nephritis. In addition, the roles of aberrant expression of microRNAs and proinflammatory cytokines have been explored. Early diagnosis is important for effective treatment and multiple biomarkers have been identified; however, none has been yet validated for clinical use. Biomarker panels may turn out to be more accurate than each individual component. Biologic agents for the treatment of lupus nephritis are being studied, including belimumab which was recently approved for nonrenal systemic lupus erythematosus. Rituximab has not proven itself in large, placebo-controlled trials, although it is still being used in refractory cases of lupus nephritis.
Summary. Lupus nephritis is a potentially devastating complication of systemic lupus erythematosus. Immune cells, cytokines, and epigenetic factors have all been recently implicated in lupus nephritis pathogenesis. These recent discoveries may enable a paradigm shift in the treatment of this complex disease, allowing the tailoring of treatment to target specific pathogenic mediators at specific points in time in the progression of disease.
Systemic lupus erythematosus (SLE) is characterized by a loss of self-tolerance and the development of autoantibodies to ubiquitous nuclear self-antigens. This autoAb production is initiated by exposure of the immune system to self-antigens via various mechanisms, including abnormal clearance of apoptotic material. In addition, the threshold for the autoimmune response is lowered by activation of the type I interferon (IFN) pathway.
SLE affects mostly women of reproductive age, with up to 20% of the cases beginning in childhood. It is a potentially devastating disease, which can involve practically any organ system. Renal involvement, termed lupus nephritis, significantly increases the morbidity and mortality of SLE patients and requires aggressive immunosuppressive therapy, which unfortunately is associated with a plethora of side-effects. The lupus nephritis histology-based classification system currently in use gives the clinician a tool to predict outcomes and to tailor therapy, albeit with moderate to good success at best. In this review, we will discuss recent advances in the understanding of lupus nephritis pathogenesis, diagnosis and monitoring of disease, as well as novel therapies (Fig. 1).
(Enlarge Image)
Figure 1.
Timeline of recent developments in the pathogenesis and treatment of lupus nephritis. BAFF, B cell activating factor; Exploratory Phase II/III SLE Evaluation of Rituximab, EXPLORER; Lupus Nephritis Assessment with Rituximab, LUNAR; systemic lupus erythematosus, SLE; TWEAK, TNF-like weak inducer of apoptosis.
Abstract and Introduction
Abstract
Purpose of Review. Renal involvement is a major cause of morbidity and mortality in systemic lupus erythematosus. In this review, we provide an update on recent discoveries in the pathogenesis, diagnosis, and treatment of lupus nephritis.
Recent Findings. Localized long-lived plasma cells have been identified as playing an important role in lupus nephritis. In addition, the roles of aberrant expression of microRNAs and proinflammatory cytokines have been explored. Early diagnosis is important for effective treatment and multiple biomarkers have been identified; however, none has been yet validated for clinical use. Biomarker panels may turn out to be more accurate than each individual component. Biologic agents for the treatment of lupus nephritis are being studied, including belimumab which was recently approved for nonrenal systemic lupus erythematosus. Rituximab has not proven itself in large, placebo-controlled trials, although it is still being used in refractory cases of lupus nephritis.
Summary. Lupus nephritis is a potentially devastating complication of systemic lupus erythematosus. Immune cells, cytokines, and epigenetic factors have all been recently implicated in lupus nephritis pathogenesis. These recent discoveries may enable a paradigm shift in the treatment of this complex disease, allowing the tailoring of treatment to target specific pathogenic mediators at specific points in time in the progression of disease.
Introduction
Systemic lupus erythematosus (SLE) is characterized by a loss of self-tolerance and the development of autoantibodies to ubiquitous nuclear self-antigens. This autoAb production is initiated by exposure of the immune system to self-antigens via various mechanisms, including abnormal clearance of apoptotic material. In addition, the threshold for the autoimmune response is lowered by activation of the type I interferon (IFN) pathway.
SLE affects mostly women of reproductive age, with up to 20% of the cases beginning in childhood. It is a potentially devastating disease, which can involve practically any organ system. Renal involvement, termed lupus nephritis, significantly increases the morbidity and mortality of SLE patients and requires aggressive immunosuppressive therapy, which unfortunately is associated with a plethora of side-effects. The lupus nephritis histology-based classification system currently in use gives the clinician a tool to predict outcomes and to tailor therapy, albeit with moderate to good success at best. In this review, we will discuss recent advances in the understanding of lupus nephritis pathogenesis, diagnosis and monitoring of disease, as well as novel therapies (Fig. 1).
(Enlarge Image)
Figure 1.
Timeline of recent developments in the pathogenesis and treatment of lupus nephritis. BAFF, B cell activating factor; Exploratory Phase II/III SLE Evaluation of Rituximab, EXPLORER; Lupus Nephritis Assessment with Rituximab, LUNAR; systemic lupus erythematosus, SLE; TWEAK, TNF-like weak inducer of apoptosis.