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Neutrophils in lupus nephritis

Nishi, Hiroshia; Mayadas, Tanya N.b

Current Opinion in Rheumatology: March 2019 - Volume 31 - Issue 2 - p 193–200
doi: 10.1097/BOR.0000000000000577
IMMUNOPATHOGENESIS AND TREATMENT OF AUTOIMMUNE DISEASES: Edited by George C. Tsokos

Purpose of review Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease characterized by IgG-autoantibodies to nuclear antigens that can deposit in the kidney and trigger lupus nephritis. Neutrophils accumulate in the kidneys of patients with proliferative LUPUS NEPHRITIS and neutrophil products and a subset of granulocytes, called low-density granulocytes (LDG) may contribute to lupus nephritis pathogenesis. Here, we will discuss recent studies implicating neutrophils in the pathogenesis of human SLE nephritis and then examine studies that provide mechanistic insights into how these cells are recruited to the glomerulus following immune complex deposition and how their products may promote lupus nephritis.

Recent findings SLE patients display unique blood transcriptional signatures linked to Type I interferon and myeloblast differentiation, which could help stratify lupus nephritis progression. Multiphoton intravital microscopy of kidney glomerular capillaries revealed a role for neutrophil FcγRs in the rapid capture of neutrophils following immune complex deposition. The view that reduced degradation of neutrophil extracellular traps (NETS) contributes to lupus nephritis progression, is now challenged by experimental data in lupus-prone mice that genetically fail to produce NETS but still are afflicted.

Summary A greater understanding of the neutrophil dependent mechanisms that promote lupus nephritis may potentially inform on newer therapeutic options that target neutrophil accumulation and reactivity in the nephritic kidney.

aDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan

bCenter for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital & Harvard Medical School, Boston, USA

Correspondence to Hiroshi Nishi, MD, PhD, Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Tel: +81 3 3815 5411; e-mail: hrnishi-tky@umin.ac.jp

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