Aberrant Levels of Hematopoietic/Neuronal Growth and Differentiation Factors in Euthyroid Women at Risk for Autoimmune Thyroid Disease

PLoS One. 2016 Apr 19;11(4):e0153892. doi: 10.1371/journal.pone.0153892. eCollection 2016.


Background: Subjects at risk for major mood disorders have a higher risk to develop autoimmune thyroid disease (AITD) and vice-versa, implying a shared pathogenesis. In mood disorder patients, an abnormal profile of hematopoietic/neuronal growth factors is observed, suggesting that growth/differentiation abnormalities of these cell lineages may predispose to mood disorders. The first objective of our study was to investigate whether an aberrant profile of these hematopoietic/neuronal growth factors is also detectable in subjects at risk for AITD. A second objective was to study the inter relationship of these factors with previously determined and published growth factors/cytokines in the same subjects.

Methods: We studied 64 TPO-Ab-negative females with at least 1 first- or second-degree relative with AITD, 32 of whom did and 32 who did not seroconvert to TPO-Ab positivity in 5-year follow-up. Subjects were compared with 32 healthy controls (HCs). We measured serum levels of brain-derived neurotrophic factor (BDNF), Stem Cell Factor (SCF), Insulin-like Growth Factor-Binding Protein 2 (IGFBP-2), Epidermal Growth Factor (EGF) and IL-7 at baseline.

Results: BDNF was significantly lower (8.2 vs 18.9 ng/ml, P<0.001), while EGF (506.9 vs 307.6 pg/ml, P = 0.003) and IGFBP-2 (388.3 vs 188.5 ng/ml, P = 0.028) were significantly higher in relatives than in HCs. Relatives who seroconverted in the next 5 years had significantly higher levels of SCF than non-seroconverters (26.5 vs 16.7 pg/ml, P = 0.017). In a cluster analysis with the previously published growth factors/cytokines SCF clustered together with IL-1β, IL-6 and CCL-3, of which high levels also preceded seroconversion.

Conclusion: Relatives of AITD patients show aberrant serum levels of 4 hematopoietic/neuronal growth factors similar to the aberrancies found in mood disorder patients, suggesting that shared growth and differentiation defects in both the hematopoietic and neuronal system may underlie thyroid autoimmunity and mood disorders. A distinct pattern of four inter correlating immune factors in the relatives preceded TPO-Ab seroconversion in the next 5 years.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain-Derived Neurotrophic Factor / blood*
  • Case-Control Studies
  • Female
  • Follow-Up Studies
  • Growth Differentiation Factors / blood*
  • Hematopoietic Cell Growth Factors / blood*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 2 / blood
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Interleukin-7 / blood
  • Mood Disorders / blood
  • Mood Disorders / metabolism
  • Nerve Growth Factors / blood*
  • Risk
  • Thyroid Gland / metabolism
  • Thyroiditis, Autoimmune / blood*
  • Thyroiditis, Autoimmune / metabolism


  • Brain-Derived Neurotrophic Factor
  • Growth Differentiation Factors
  • Hematopoietic Cell Growth Factors
  • Insulin-Like Growth Factor Binding Protein 2
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-7
  • Nerve Growth Factors

Grant support

HAD was supported by: PSYCHAID, seventh framework program, IAPP, 286334. RPP was supported by: Zon-MW TOP grant (number 91212044) and an Erasmus MC MRACE grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.