Amino acid sequence homology between thyroid autoantigens and central nervous system proteins: Implications for the steroid-responsive encephalopathy associated with autoimmune thyroiditis

Benvenga, Salvatore; Antonelli, Alessandro; Fallahi, Poupak; Bonanno, Carmen; Rodolico, Carmelo; Guarneri, Fabrizio

doi:10.1016/j.jcte.2021.100274

Cited by 4 publications

(3 citation statements)

References 101 publications

(216 reference statements)

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“…Furthermore, one of the several mechanistic hypotheses underlying the coincidence of multiple autoimmune conditions is that various tissues share the same epitopes, to which autoantibodies can cross-react. 42 In this context, Benvenga et al 43 recently showed an interesting amino acid sequence homology between thyroid autoantigens and central nervous system proteins, including TPO, autoantibodies to which are a characteristic biomarker for Hashimoto's hypothyroidism.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Genetic Link Between Thyroid Dysfunction and Common Psychiatric Disorders: A Specific Hormonal or a General Autoimmune Comorbidity

Soheili-Nezhad

Sprooten

Tendolkar³

et al. 2023

Thyroid

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Background: The hypothalamus-pituitary-thyroid axis coordinates brain development and postdevelopmental function. Thyroid hormone (TH) variations, even within the normal range, have been associated with the risk of developing common psychiatric disorders, although the underlying mechanisms remain poorly understood. Methods: To get new insight into the potentially shared mechanisms underlying thyroid dysfunction and psychiatric disorders, we performed a comprehensive analysis of multiple phenotypic and genotypic databases. We investigated the relationship of thyroid disorders with depression, bipolar disorder (BIP), and anxiety disorders (ANXs) in 497,726 subjects from U.K. Biobank. We subsequently investigated genetic correlations between thyroid disorders, thyrotropin (TSH), and free thyroxine (fT4) levels, with the genome-wide factors that predispose to psychiatric disorders. Finally, the observed global genetic correlations were furthermore pinpointed to specific local genomic regions. Results: Hypothyroidism was positively associated with an increased risk of major depressive disorder (MDD; OR = 1.31, p = 5.29 × 10 −89 ), BIP (OR = 1.55, p = 0.0038), and ANX (OR = 1.16, p = 6.22 × 10 −8 ). Hyperthyroidism was associated with MDD (OR = 1.11, p = 0.0034) and ANX (OR = 1.34, p = 5.99 × 10 − ⁶). Genetically, strong coheritability was observed between thyroid disease and both major depressive ( r g = 0.17, p = 2.7 × 10 − ⁴) and ANXs ( r g = 0.17, p = 6.7 × 10 − ⁶). This genetic correlation was particularly strong at the major histocompatibility complex locus on chromosome 6 ( p < 10 − ⁵), but further analysis showed that other parts of the genome also contributed to this global effect. Importantly, neither TSH nor fT4 levels were genetically correlated with mood disorders. Conclusions: Our findings highlight an underlying association between autoimmune hypothyroidism and mood disorders, which is not mediated through THs and in which autoimmunity plays a prominent role. While these findings could shed new light on the potential ineffectiveness of treating (minor) variations in thyroid function in psychiatric disorders, further research is needed to identify the exact underlying molecular mechanisms.

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Section: Discussionmentioning

confidence: 99%

Exploring the Genetic Link Between Thyroid Dysfunction and Common Psychiatric Disorders: A Specific Hormonal or a General Autoimmune Comorbidity

Soheili-Nezhad

Sprooten

Tendolkar³

et al. 2023

Thyroid

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“…The CNS areas where those proteins are expressed match CNS areas where pathological findings were detected at biopsy and/or by neuroimaging in patients in HE. They also mentioned the involvement in other autoimmune disorders of the proteins they found ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

The use of intravenous immunoglobulin in the treatment of Hashimoto’s encephalopathy: case based review

Şorodoc,

Constantin,

Asaftei

et al. 2023

Front. Neurol.

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BackgroundHashimoto’s encephalopathy (HE) is a controversial immunological neuropsychiatric disease, with a poorly understood pathogenesis. It is characterized by symptoms of acute or subacute encephalopathy which usually occur in the presence of elevated levels of antithyroid antibodies. Even though it is also known as steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT), some cases appear to be steroid-resistant. This review examined whether treatment of Hashimoto’s encephalopathy with intravenous immunoglobulin (IVIG) is associated with better clinical outcomes than the standard therapy. Additionally, we presented a case of a 59-year-old man who presented with severe neurological manifestations and was successfully treated with intravenous immunoglobulin.MethodsThe online databases PubMed and EMBASE were searched.ResultsA total of 1,365 articles were identified. After the deletion of 112 duplicates, 1,253 studies were screened by evaluating the title and abstract, focusing on Hashimoto’s encephalopathy cases where IVIG were used. 846 studies were excluded because they were not relevant to the topic or included pediatric population. Therefore, 407 full-text articles were assessed for eligibility. The final analysis included 14 eligible articles after 393 were excluded (irrelevant texts, not written in English, full-text not available). In the majority of the selected case-reports, IVIG was associated with a good outcome, sometimes even with dramatic improvements in patient’s status.ConclusionIn last years, intravenous immunoglobulin therapy proved its utility in Hashimoto’s encephalopathy’s treatment, being a well tolerated therapy associated with remarkable improvement in patient’s status. Further research is still needed in order to define the optimal treatment protocol for Hashimoto’s encephalopathy and to establish if intravenous immunoglobulin can also be used as a first-line therapy, alone or in combination with steroids.

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“…Furthermore, one of the several mechanistic hypotheses underlying the coincidence of multiple autoimmune conditions is that various tissues share the same epitopes, to which autoantibodies can cross-react [39]. In this context, Benvenga et al [40] recently showed an interesting amino acid sequence homology between thyroid autoantigens and central nervous system proteins, including thyroid peroxidase, autoantibodies to which are a characteristic biomarker for Hashimoto’s hypothyroidism.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Genetic Link Between Thyroid Dysfunction and Common Psychiatric Disorders: a Specific Hormonal, or a General Autoimmune Comorbidity

Soheili-Nezhad

Sprooten

Tendolkar³

et al. 2022

Preprint

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BackgroundThe hypothalamus-pituitary-thyroid axis coordinates brain development and post-developmental function. Thyroid hormone variations, even within the normal range, have been associated with the risk of developing common psychiatric disorders, although the underlying mechanisms remain poorly understood.Materials and methodsTo get new insight into the potentially shared mechanisms underlying thyroid dysfunction and psychiatric disorders, we performed a comprehensive analysis of multiple phenotypic and genotypic databases. We investigated the relationship of thyroid disorders with depression, bipolar disorder, and anxiety disorders in 502,480 subjects from UK Biobank. We subsequently investigated genetic correlations between thyroid disorders, thyroid stimulating hormone (TSH) and free T4 (FT4) levels, with the genome-wide factors that predispose to psychiatric disorders. Finally, the observed global genetic correlations were furthermore pinpointed to specific local genomic regions.ResultsHypothyroidism was positively associated with an increased risk of major depressive disorder (OR=1.51, p<10−16) and bipolar disorder (OR=1.99, p=2.1×10−6). Genetically, strong coheritability was observed between autoimmune hypothyroidism and both major depressive (rg=0.17, p=2.7×10−4) and anxiety disorders (rg=0.17, p=6.7×10−6). This genetic correlation was particularly strong at the Major Histocompatibility Complex (MHC) locus on chromosome six (p<10−5), but further analysis showed that other parts of the genome also contributed to this global effect. Importantly, neither TSH nor FT4 levels were genetically correlated with mood disorders.ConclusionOur findings highlight an underlying association between autoimmune hypothyroidism and mood disorders, which is not mediated via thyroid hormones, and in which autoimmunity plays a prominent role. While these findings could shed new light on the potential ineffectiveness of treating (minor) variations in thyroid function in psychiatric disorders, further research is needed to identify the exact underlying molecular mechanisms.

show abstract

Amino acid sequence homology between thyroid autoantigens and central nervous system proteins: Implications for the steroid-responsive encephalopathy associated with autoimmune thyroiditis

Cited by 4 publications

References 101 publications

Exploring the Genetic Link Between Thyroid Dysfunction and Common Psychiatric Disorders: A Specific Hormonal or a General Autoimmune Comorbidity

Exploring the Genetic Link Between Thyroid Dysfunction and Common Psychiatric Disorders: A Specific Hormonal or a General Autoimmune Comorbidity

The use of intravenous immunoglobulin in the treatment of Hashimoto’s encephalopathy: case based review

Exploring the Genetic Link Between Thyroid Dysfunction and Common Psychiatric Disorders: a Specific Hormonal, or a General Autoimmune Comorbidity

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