Targeting Regulatory T Cells for Therapy of Lupus Nephritis

Lupus glomerulonephritis (LN) is a complex autoimmune disease characterized by circulating autoantibodies, immune-complex deposition, immune dysregulation and defects in regulatory T cell (Tregs). Treatment options rely on general immunosuppressants and steroids that have serious side effects. Approaches to target immune cells, such as B cells in particular, has had limited success and new approaches are being investigated. Defects in Tregs in the setting of autoimmunity is well known and Treg-replacement strategies are currently being explored. The aim of this minireview is to rekindle interest on Treg-targeting strategies. We discuss the existing evidences for Treg-enhancement strategies using key cytokines interleukin (IL)-2, IL-33 and IL-6 that have shown to provide remission in LN. We also discuss strategies for indirect Treg-modulation for protection from LN.

Microscopic Polyangitis in Pediatric Systemic Lupus Erythematosus: A Unique Presentation of Pulmonary - Renal Syndrome and Case Report of an Overlap Syndrome

Background: Secondary vasculitis is encountered in about one third of all cases of systemic lupus erythematosus (SLE). Skin is most commonly involved in lupus-related small vasculitis. Although antineutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) is relatively uncommon, it can be the most dangerous manifestation associated with high mortality. SLE and AAV are separate diseases with different pathophysiologies and an overlap syndrome has only been reported few times in previous literature. Case Presentation: We present a unique case of a pediatric patient of pulmonary-renal syndrome, presenting with pulmonary alveolar hemorrhage and rapidly progressive glomerulonephritis. Serological and biopsy findings were suggestive of SLE and AAV occurring simultaneously. Renal biopsy demonstrated necrotizing and crescentic glomerulonephritis, superimposed on diffuse segmental proliferative lupus glomerulonephritis class IV. Conclusions: Presentations of autoimmune diseases and vasculitis can be multi-systemic. Considering overlap syndromes, especially in patients with underlying connective tissue disease or systemic vasculitis, is vital for prompt therapy and prevention of morbidity in this population.

Podocyte Injury in Lupus Nephritis

Systemic lupus erythematosus (SLE) is characterized by a broad spectrum of renal lesions. In lupus glomerulonephritis, histological classifications are based on immune-complex (IC) deposits and hypercellularity lesions (mesangial and/or endocapillary) in the glomeruli. However, there is compelling evidence to suggest that glomerular epithelial cells, and podocytes in particular, are also involved in glomerular injury in patients with SLE. Podocytes now appear to be not only subject to collateral damage due to glomerular capillary lesions secondary to IC and inflammatory processes, but they are also a potential direct target in lupus nephritis. Improvements in our understanding of podocyte injury could improve the classification of lupus glomerulonephritis. Indeed, podocyte injury may be prominent in two major presentations: lupus podocytopathy and glomerular crescent formation, in which glomerular parietal epithelial cells play also a key role. We review here the contribution of podocyte impairment to different presentations of lupus nephritis, focusing on the podocyte signaling pathways involved in these lesions.