Neutrophil Extracellular Traps in Plasma from Dogs with Immune-mediated Hemolytic Anemia

J Vet Intern Med. 2018 Jan;32(1):128-134. doi: 10.1111/jvim.14881. Epub 2017 Dec 7.

Abstract

Background: Neutrophil extracellular traps (NETs) are part of the innate immune response and are essential in local pathogen control, but are associated with pathological inflammation, organ damage, autoimmunity, and thrombosis. Immune-mediated hemolytic anemia (IMHA) is a pro-inflammatory, prothrombotic disease associated with high mortality.

Hypothesis/objectives: Neutrophil extracellular traps (NETs) are a feature of the inflammatory process in dogs with IMHA. The objective of the study was to evaluate plasma from dogs with IMHA for the presence of 2 indirect markers and 1 direct marker of NETs.

Animals: Healthy client-owned dogs (56) and hospitalized dogs with IMHA (n = 35).

Methods: Prospective study. Plasma samples for all dogs were evaluated for cell-free DNA using a fluorescence assay, histone-DNA (hisDNA) complex using an ELISA, and citrullinated histone H3 (specific for NETosis) using Western blot. Reference intervals were generated using plasma from healthy dogs.

Results: In dogs with IMHA, cell-free DNA concentration was above the reference interval in 17% of samples with a median (range) of 1.0 μg/mL (0.1-17.3), and hisDNA concentration was above the reference interval in 94% of samples with a median (range) of 30.7 × pooled normal plasma (PNP; 0.6-372.1). Western blot for citrullinated histone H3 identified detectable bands in 84% samples from dogs with IMHA.

Conclusions and clinical importance: The assay for cell-free DNA detected evidence of NETs in fewer dogs than did the other approaches. Excessive NETs appears to be a feature of IMHA in dogs and contributions to the prothrombotic state deserve further study.

Keywords: DNA; Histone; IMHA; Inflammation.

MeSH terms

  • Anemia, Hemolytic, Autoimmune / veterinary*
  • Animals
  • Biomarkers
  • Cell-Free Nucleic Acids / blood
  • Dog Diseases / blood*
  • Dog Diseases / immunology
  • Dogs
  • Extracellular Traps*
  • Histones / blood
  • Inflammation
  • Prospective Studies
  • Reference Values

Substances

  • Biomarkers
  • Cell-Free Nucleic Acids
  • Histones