Article Text

Download PDFPDF

204 The role of neutrophils in the clinical severity of lupus nephritis patients with concurrent skin disease
  1. Lais Osmani,
  2. Jason Pettus,
  3. Alecia Roy and
  4. Sladjana Skopelja-Gardner
  1. Dartmouth Hitchcock Medical Center, Lebanon NH, USA


Background Skin disease affects >80% of lupus patients and has been linked to lupus nephritis (LN) flares. We recently found that skin inflammation caused by ultraviolet light leads to increased expression of renal inflammatory and injury markers as well as proteinuria, mediated by neutrophils, which migrated from the inflamed skin to the kidneys. These data prompted the hypothesis that presence of concurrent skin disease in lupus patients leads to worse nephritis mediated by neutrophils.

Methods Lupus nephritis biopsies (n=43) were retrieved from the Dartmouth Hitchcock Medical Center tissue bank and grouped: (i) LN with concurrent skin rash (malar, subacute, or discoid n =15) and (ii) LN without any rash (n=6) at the time of LN diagnosis (class IV). Patients with inconclusive or incomplete skin findings were excluded. The study included only female patients. Clinical and laboratory data (absolute neutrophil (ANC) and lymphocyte (ALC) counts, serum creatinine, glomerular filtration rate (GFR), autoantibody titers, and complement) were collected by chart review. Histologic and immunofluorescence data were extracted from biopsy reports. Student’s t-test was performed to detect statistical significance between patient groups.

Results Presence of skin rash at the time of LN flare was indicative of more active disease, reflected by higher ANA, anti-dsDNA IgG, and low C3 and C4 levels. LN patients with concurrent skin disease had a higher neutrophil count (p < 0.05) and neutrophil-lymphocyte ratio (p< 0.01), but not ALC, compared to LN patients without a concurrent skin rash. High neutrophil counts in the presence of skin disease associated with lower GFR (< 60; p< 0.01). This association was not seen in the absence of concurrent skin disease and rash alone did not predict GFR. Analysis of kidney immunofluorescence revealed that concurrent skin disease at the time of LN flare associated with greater IgA deposition. Increased renal IgA levels associated with higher neutrophil but not lymphocyte counts (p < 0.01). This was specific to IgA as no associations with IgG or IgM deposition were detected.

Conclusions Our study provides novel findings that suggest neutrophils may be the pathogenic link between skin inflammation and LN: (i) higher neutrophil counts are found in the presence of a skin rash at the time of LN flare, (ii) neutrophilia but not lymphocytosis in the presence of a skin rash associates with worse kidney function, and (iii) high neutrophils in the presence of skin rash associate with increased renal IgA. These data provide a novel model of IgA-driven activation of neutrophils leading to kidney injury initiated by skin inflammation.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.