Antibody to CMRF35-Like Molecule 2, CD300e A Novel Biomarker Detected in Patients with Fulminant Type 1 Diabetes

PLoS One. 2016 Aug 11;11(8):e0160576. doi: 10.1371/journal.pone.0160576. eCollection 2016.

Abstract

Aims/hypothesis: Fulminant type 1 diabetes (FT1D) is a distinct subtype of type 1 diabetes and is fatal without immediate diagnosis and treatment. At present, there are no biomarkers for early and predictive detection of FT1D.

Methods: First, we analyzed a total of 6 serum samples from 3 patients with FT1D (1 sample in the acute and 1 in the sub-acute phases from each patient) by seromic analysis. Second, titres of the antibody were measured by ELISA in sera from 30 patients with FT1D (both in the acute and sub-acute phases), 13 patients with FT1D in the chronic phase, 32 patients with autoimmune type 1 (type 1A) diabetes (T1AD), 30 patients with type 2 diabetes (T2D), 23 patients with autoimmune thyroid disease (AITD) and 31 healthy control subjects (HC).

Results: Seromic analysis revealed 9 antibodies which showed high signals from all 3 patients with FT1D in the acute phase. Among them, the titre of anti-CD300e antibody was significantly higher in FT1D patients in the acute phase than that in T1AD, T2D, AITD patients and HC, as determined by ELISA (P<0.01, respectively). The titre of anti-CD300e antibody was also higher in FT1D in the acute phase than that in the sub-acute phase (P = 0.0018, Wilcoxon signed-rank test). The titre of anti-LGALS3 antibody in FT1D patients in the acute phase did not differ from that in patients with FT1D in the sub-acute phase, T1AD, T2D, AITD and HC.

Conclusion/interpretation: The titre of a novel antibody, anti-CD300e, was high in sera from patients with FT1D. This antibody might be a diagnostic marker and provide new insight into the pathogenesis of FT1D.

MeSH terms

  • Adult
  • Antigens, Surface / immunology*
  • Autoantibodies / blood*
  • Biomarkers / blood*
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / diagnosis*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • HEK293 Cells
  • Humans
  • Male
  • Membrane Glycoproteins / immunology*
  • Middle Aged
  • ROC Curve

Substances

  • Antigens, Surface
  • Autoantibodies
  • Biomarkers
  • CD300C protein, human
  • Membrane Glycoproteins

Grants and funding

This study was supported by a Novo Nordisk Pharma-Insulin Research Grant received by FH, a Junior Scientist Development Grant supported by Novo Nordisk Pharma Ltd received by FH, and a Grant-in-Aid from the Japanese Society for the Promotion of Science (KAKENHI 15K09402) received by TH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.