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


CONCLUSIONS
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.
Division of Endocrinology, Department of Internal Medicine, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.|Rotterdam Thyroid Center, Department of Internal Medicine, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.
Elske T
ET
Massolt
Internal Medicine Department, Endocrinology Section, Nykøbing Falster Hospital, Fjordvej 15, 4800, Nykøbing Falster, Denmark.
Grigoris
G
Effraimidis
Division of Endocrinology, Department of Internal Medicine, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.|Rotterdam Thyroid Center, Department of Internal Medicine, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.
Tim I M
TI
Korevaar
Academical Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
Wilmar M
WM
Wiersinga
Division of Endocrinology, Department of Internal Medicine, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.|Rotterdam Thyroid Center, Department of Internal Medicine, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.
W Edward
WE
Visser
Division of Endocrinology, Department of Internal Medicine, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.|Rotterdam Thyroid Center, Department of Internal Medicine, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.
Robin P
RP
Peeters
Department of Immunology, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.
Hemmo A
HA
Drexhage
D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D055412:Growth Differentiation Factors / Q000097:blood*; D016298:Hematopoietic Cell Growth Factors / Q000097:blood*; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D015851:Interleukin-7 / Q000097:blood; D019964:Mood Disorders / Q000097:blood / Q000378:metabolism; D009414:Nerve Growth Factors / Q000097:blood*; D012306:Risk; D013961:Thyroid Gland / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000097:blood* / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D055412:Growth Differentiation Factors; D016298:Hematopoietic Cell Growth Factors; D018971:Insulin-Like Growth Factor Binding Protein 2; D053583:Interleukin-1beta; D015850:Interleukin-6; D015851:Interleukin-7; D009414:Nerve Growth Factors