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

Massolt ET, Effraimidis G, Korevaar TI, Wiersinga WM, Visser WE, Peeters RP, Drexhage HA - PLoS ONE (2016)

Bottom Line: Subjects were compared with 32 healthy controls (HCs).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).

View Article: PubMed Central - PubMed

Affiliation: Division of Endocrinology, Department of Internal Medicine, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Cluster analysis.Heat map of hierarchical cluster analysis of the serum levels of cytokines, chemokines, growth factors and tissue remodeling factors in the relatives. Color-coded correlation matrix illustrates Pearson’s correlation coefficients. Significant positive correlations are given in the red scale (darkest red are correlation coefficients > 0.50), and significant negative correlations are given in the (dark) green scale. Lighter fields are not significant. In addition, a dendrogram is presented as a result of the hierarchical clustering. A indicates cluster A and B indicates cluster B.
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pone.0153892.g001: Cluster analysis.Heat map of hierarchical cluster analysis of the serum levels of cytokines, chemokines, growth factors and tissue remodeling factors in the relatives. Color-coded correlation matrix illustrates Pearson’s correlation coefficients. Significant positive correlations are given in the red scale (darkest red are correlation coefficients > 0.50), and significant negative correlations are given in the (dark) green scale. Lighter fields are not significant. In addition, a dendrogram is presented as a result of the hierarchical clustering. A indicates cluster A and B indicates cluster B.

Mentions: Taking the analytes which we have previously determined also into account we found in the cluster analysis two mutually correlating clusters of analytes: one stronger inter correlating cluster A and a weaker inter correlating cluster B (Fig 1) [11]. Cluster A contained the inflammatory cytokines/chemokines IL-1β, CCL3 and IL-6, the connective tissue modulator MMP-13 and the hematopoietic/neuronal growth and differentiation factor SCF, while cluster B contained the pro-inflammatory chemokines CCL2 and CCL4, the endothelial adhesion molecule sVCAM-1, PDGF-BB, and the T cell and NK cell growth factor IL-7. The heat map shows that the growth factors IGFBP-2, EGF and BDNF barely correlated to each other and to the other analytes.


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

Massolt ET, Effraimidis G, Korevaar TI, Wiersinga WM, Visser WE, Peeters RP, Drexhage HA - PLoS ONE (2016)

Cluster analysis.Heat map of hierarchical cluster analysis of the serum levels of cytokines, chemokines, growth factors and tissue remodeling factors in the relatives. Color-coded correlation matrix illustrates Pearson’s correlation coefficients. Significant positive correlations are given in the red scale (darkest red are correlation coefficients > 0.50), and significant negative correlations are given in the (dark) green scale. Lighter fields are not significant. In addition, a dendrogram is presented as a result of the hierarchical clustering. A indicates cluster A and B indicates cluster B.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4836766&req=5

pone.0153892.g001: Cluster analysis.Heat map of hierarchical cluster analysis of the serum levels of cytokines, chemokines, growth factors and tissue remodeling factors in the relatives. Color-coded correlation matrix illustrates Pearson’s correlation coefficients. Significant positive correlations are given in the red scale (darkest red are correlation coefficients > 0.50), and significant negative correlations are given in the (dark) green scale. Lighter fields are not significant. In addition, a dendrogram is presented as a result of the hierarchical clustering. A indicates cluster A and B indicates cluster B.
Mentions: Taking the analytes which we have previously determined also into account we found in the cluster analysis two mutually correlating clusters of analytes: one stronger inter correlating cluster A and a weaker inter correlating cluster B (Fig 1) [11]. Cluster A contained the inflammatory cytokines/chemokines IL-1β, CCL3 and IL-6, the connective tissue modulator MMP-13 and the hematopoietic/neuronal growth and differentiation factor SCF, while cluster B contained the pro-inflammatory chemokines CCL2 and CCL4, the endothelial adhesion molecule sVCAM-1, PDGF-BB, and the T cell and NK cell growth factor IL-7. The heat map shows that the growth factors IGFBP-2, EGF and BDNF barely correlated to each other and to the other analytes.

Bottom Line: Subjects were compared with 32 healthy controls (HCs).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).

View Article: PubMed Central - PubMed

Affiliation: Division of Endocrinology, Department of Internal Medicine, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus