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Abstract: FR-PO596

IgE Double-Stranded DNA Antibody-Containing Serum From Systemic Lupus Erythematosus Patients With Nephritis Alters the Inflammatory Profile of Basophils, Neutrophils, and Eosinophils

Session Information

Category: Glomerular Diseases

  • 1302 Glomerular Diseases: Immunology and Inflammation

Authors

  • Sendic, Senka, Karolinska Institutet, Department of Clinical Sciences, Stockholm, Sweden
  • Mansouri, Ladan, Karolinska Institutet, Department of Clinical Science and Education Södersjukhuset, Stockholm, Sweden
  • Nopp, Anna, Karolinska Institutet, Department of Clinical Science and Education Södersjukhuset, Stockholm, Sweden
  • Gunnarsson, Iva, Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
  • Jacobson, Stefan H., Karolinska Institutet, Department of Clinical Sciences, Stockholm, Sweden
  • Lundahl, Joachim, Karolinska Institutet, Department of Clinical Science and Education Södersjukhuset, Stockholm, Sweden
Background

Lupus nephritis (LN) is characterized by primarily IgG autoantibodies against double stranded DNA (dsDNA). Recently, attention has been paid to the role of IgE dsDNA antibodies (auto IgE dsDNA) and the involvement of basophils and neutrophils in the pathogenesis. Therefore, we studied the prevalence of IgE dsDNA antibodies in patients with SLE and in healthy controls and the impact of sera on the phenotypic profile of basophils, neutrophils and eosinophils.

Methods

In this cross-sectional study 87 patients with SLE were included from the Dep. of Rheumatology, Karolinska University Hospital, Stockholm, Sweden. Disease activity was assessed using the British Isles Lupus Assessment Group (BILAG) index. Sixty-three patients with active nephritis (BILAG A-C) and twenty-four patients had previously active but currently quiescent renal SLE (BILAG D). Forty-one healthy controls were included. Serum levels of auto IgE dsDNA were measured with fluorescence enzyme immunoassay. In a subgroup including 10 patients (BILAG A) and 10 healthy controls, a whole blood method was applied to evaluate the impact of serum on granulocyte subpopulations. Cells were immune stained for markers related to degranulation, adhesion and immune modulation and analyzed by flow cytometry.

Results

Patients with active nephritis (BILAG A-C), but not patients with BILAG D, had a significant higher level of autoreactive IgEdsDNA compared to healthy individuals (p=0.030, p=1.0, respectively). Patient sera, but not healthy control sera, up-regulated CD69 on basophils (p=0.023) and patient sera down-regulated CD164 to a higher extent than sera from healthy controls (p=0.043). Patient sera, but not healthy control sera, down-regulated neutrophil expression of CD44 and CD15 (p=0.009 and p=0.029, respectively). CD88 on eosinophils was down-regulated by patient sera to a higher extent than sera from healthy individuals (p=0.001).

Conclusion

Patients with active LN , but not patients with currently quiescent renal SLE, have a significant higher level of circulating autoreactive IgEdsDNA than healthy controls and sera from these patients impact the phenotypic profile of basophils, neutrophils and eosinophils. These data indicate a role of these cells in the pathogenesis of LN and may impact treatment strategies.