In this Review, Tsokos et al. describe recent advances in our understanding of systemic lupus erythematosus (SLE) that are driving repurposing of existing drugs as well as development of new treatments. Cytokines, tolerance pathways, local tissue mediators, and epigenetic mechanisms all show promise as novel targeted therapies that could lead to individualized care in SLE.

New insights into the immunopathogenesis of systemic lupus erythematosus

Background Anifrolumab, a human monoclonal antibody to type I interferon receptor subunit 1 investigated for the treatment of systemic lupus erythematosus (SLE), did not have a significant...

/pdf/trial-of-anifrolumab-in-active-systemic-lupus-erythematosus-2867skdlp1.pdf

Trial of Anifrolumab in Active Systemic Lupus Erythematosus

SLE is a chronic inflammatory disease that affects the kidneys in about 50% of patients. Lupus nephritis is a major risk factor for overall morbidity and mortality in SLE, and despite potent anti-inflammatory and immunosuppressive therapies still ends in CKD or ESRD for too many patients. This review highlights recent updates in our understanding of disease epidemiology, genetics, pathogenesis, and treatment in an effort to establish a framework for lupus nephritis management that is patient-specific and oriented toward maintaining long-term kidney function in patients with lupus.

/pdf/update-on-lupus-nephritis-400k9b4g2u.pdf

Update on Lupus Nephritis

Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies.

/pdf/the-immune-cell-landscape-in-kidneys-of-patients-with-lupus-2jvorgdc3g.pdf

The immune cell landscape in kidneys of patients with lupus nephritis

The human immune system is highly variable between individuals but relatively stable over time within a given person. Recent conceptual and technological advances have enabled systems immunology analyses, which reveal the composition of immune cells and proteins in populations of healthy individuals. The range of variation and some specific influences that shape an individual's immune system is now becoming clearer. Human immune systems vary as a consequence of heritable and non-heritable influences, but symbiotic and pathogenic microbes and other non-heritable influences explain most of this variation. Understanding when and how such influences shape the human immune system is key for defining metrics of immunological health and understanding the risk of immune-mediated and infectious diseases.

/pdf/human-immune-system-variation-30f2hzfy9e.pdf

Human immune system variation

https://www.cell.com/cell/pdf/S0092-8674(16)30660-2.pdf

Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients.

Erratum: Personalized immunomonitoring uncovers molecular networks that stratify lupus patients ((Cell (2016) 165 (551-565))

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Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients.

Erratum: Personalized immunomonitoring uncovers molecular networks that stratify lupus patients ((Cell (2016) 165 (551-565))