Abstract
BackgroundSubjects 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.MethodsWe 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.ResultsBDNF 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.ConclusionRelatives 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.
Highlights
We studied 64 Thyroid peroxidase (TPO)-Ab-negative females with at least 1 first- or second-degree relative with autoimmune thyroid disease (AITD), 32 of whom did and 32 who did not seroconvert to TPO antibodies (TPO-Abs) positivity in 5-year followup
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
Autoimmune hypothyroidism is characterized by a combination of clinical features, elevated serum TSH with reduced free T4 (FT4) levels, the presence of serum antibodies against thyroid antigens, and reduced echogenicity of the thyroid sonogram [1]
Summary
Autoimmune hypothyroidism is characterized by a combination of clinical features, elevated serum TSH with reduced free T4 (FT4) levels, the presence of serum antibodies against thyroid antigens, and reduced echogenicity of the thyroid sonogram [1]. It is the most common organspecific autoimmune disorder with an estimated prevalence of 2%, with a higher prevalence in women and depending on iodine intake [2,3,4,5]. In the Whickham follow-up study, women with TPO-Abs had an eight-fold higher risk of developing clinically overt hypothyroidism over 20 years than did antibody-negative women [7]. A second objective was to study the inter relationship of these factors with previously determined and published growth factors/cytokines in the same subjects
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