Cellular aspects of the pathogenesis of lupus nephritis

Purpose of review Lupus nephritis is a common severe manifestation of systemic lupus erythematosus. Despite recent advances in therapeutics and understanding of its pathogenesis, there are still substantial unmet needs. This review discusses recent discoveries in these areas, especially the role of tubulointerstitial inflammation (TII) in lupus nephritis. Recent findings Non-white ethnicity is still a major risk and poor prognostic factor in lupus nephritis. TII and fibrosis have been found to be associated with worse renal outcome but the current lupus nephritis treatment guidelines and trials are based on the degree of glomerular inflammation. In combination with mycophenolate mofetil, a B-cell-targeted therapy (belimumab) and a calcineurin inhibitor (voclosporin) have shown efficacy in recent lupus nephritis trials. However, response rates have been modest. While lupus glomerulonephritis results from immune complex deposition derived from systemic autoantibodies, TII arises from complex processes associated with in situ adaptive cell networks. These include local antibody production, and cognate or antigen-induced interactions between T follicular helper cells, and likely other T-cell populations, with antigen presenting cells including B cells, myeloid dendritic cells and plasmacytoid dendritic cells. Better understanding of the pathogenesis of TII will identify novel therapeutic targets predicted to improve outcomes in our patients with lupus nephritis.

Automated summary

Despite recent advances, there are still substantial unmet needs in the treatment of lupus nephritis. Non-white ethnicity remains a major risk factor. Recent findings suggest that tubulointerstitial inflammation and fibrosis are associated with renal outcomes, yet current treatment guidelines focus on glomerular inflammation. Combination therapies involving B-cell-targeted and calcineurin inhibitor have shown efficacy in trials, but response rates are modest. Understanding the pathogenesis of tubulointerstitial inflammation may lead to novel therapeutic targets for improving outcomes in patients with lupus nephritis.