Thyroid autoimmunity as a window to autoimmunity: An explanation for sex differences in the prevalence of thyroid autoimmunity

Merrill, Stephen J.; Mu, Ying

doi:10.1016/j.jtbi.2014.12.015

Cited by 58 publications

(52 citation statements)

References 66 publications

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“…Regression analyses of men and women stratified into obese (BMI > 30) or nonobese (BMI ≤ 30) subgroups showed that increased leptin levels correlate with thyroid autoantibodies in nonobese males, but not in obese males or in females. These findings underscore the influence of sex and obesity on autoimmunity and highlight sex differences in the potential role of leptin in promoting autoimmune thyroid disease.…”

Section: Discussionmentioning

confidence: 56%

Increased leptin levels correlate with thyroid autoantibodies in nonobese males

MacIver

Thomas

Green

et al. 2015

Clinical Endocrinology

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SummaryObjective Leptin is an adipokine that regulates body weight and appetite. It is also an inflammatory cytokine that influences immune reactivity and autoimmunity. Leptin levels are increased in obesity and are higher in women than in men. We aimed to determine whether leptin levels, independent of sex and body mass index (BMI), are associated with thyroid autoimmunity. Design This study uses data from The Third National Health and Nutrition Examination Survey (NHANES III) to test the association of leptin and thyroid autoimmunity, independent of BMI. Measurements Thyroid-stimulating hormone, thyroxine, antithyroid peroxidase (TPO) antibodies and leptin levels were measured in 2902 men and 3280 women within the NHANES III population. BMI was calculated from height and weight. Results Women had significantly higher leptin levels and anti-TPO antibody titres than men. Correlation analyses demonstrated that leptin levels were associated with anti-TPO antibody levels in the total population, but when men and women were analysed separately, this association was lost. We then stratified men and women into obese (BMI > 30) or nonobese (BMI ≤ 30) subgroups and determined the association between leptin levels and anti-TPO antibody titres for each subgroup. Using regression analysis, we found that increased leptin levels correlated with thyroid autoantibodies in nonobese males, but not in obese males or in females. Conclusions Leptin levels correlated with thyroid autoantibody titres in nonobese males. This association was not found in females. Sex and body habitus should therefore be considered in studying the role of leptin in other autoimmune conditions.

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Section: Discussionmentioning

confidence: 56%

Increased leptin levels correlate with thyroid autoantibodies in nonobese males

MacIver

Thomas

Green

et al. 2015

Clinical Endocrinology

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“…Endocrine problems are not uncommon in patients with autoimmune disorders [44], and the female bias towards thyroid diseases has been extensively documented [45–48]. Furthermore, since the predominantly female incidence of hypothyroidism corresponds with the female susceptibility to autoimmune diseases, the thyroid gland has been proposed as a decisive organ to explain the sex skewness in autoimmune diseases.…”

Section: Discussionmentioning

confidence: 99%

“…The effect of adipokines, which comprise a number of different cytokines including, e.g., leptins, adiponectins, TNF-α, and IL-6, on thyroid tissue has been suggested as a triggering mechanism for autoimmune thyroiditis, which probably precedes or coincides with the diagnosis of another systemic autoimmune disease such as pSS and SLE. [44]. This emphasizes the need for a comprehensive screening and close monitoring of thyroid function in suspected patients because it might be an important marker for autoimmune disease development.…”

Section: Discussionmentioning

confidence: 99%

Long-term follow-up in primary Sjögren’s syndrome reveals differences in clinical presentation between female and male patients

et al. 2017

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BackgroundDespite men being less prone to develop autoimmune diseases, male sex has been associated with a more severe disease course in several systemic autoimmune diseases. In the present study, we aimed to investigate differences in the clinical presentation of primary Sjögren’s syndrome (pSS) between the sexes and establish whether male sex is associated with a more severe form of long-term pSS.MethodsOur study population included 967 patients with pSS (899 females and 68 males) from Scandinavian clinical centers. The mean follow-up time (years) was 8.8 ± 7.6 for women and 8.5 ± 6.2 for men (ns). Clinical data including serological and hematological parameters and glandular and extraglandular manifestations were compared between men and women.ResultsMale patient serology was characterized by more frequent positivity for anti-Ro/SSA and anti-La/SSB (p = 0.02), and ANA (p = 0.02). Further, men with pSS were more frequently diagnosed with interstitial lung disease (p = 0.008), lymphadenopathy (p = 0.04) and lymphoma (p = 0.007). Conversely, concomitant hypothyroidism was more common among female patients (p = 0.009).ConclusionsWe observe enhanced serological responses and higher frequencies of lymphoma-related extraglandular manifestations in men with pSS. Notably, lymphoma itself was also significantly more common in men. These observations may reflect an aggravated immune activation and a more severe pathophysiological state in male patients with pSS and indicate a personalized managing of the disease due to the influence of the sex of patients with pSS.

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“…Also, antigen presentation, complement system, apoptosis and pattern recognition receptors are known to involve in thyroid autoimmunity [62–65]. …”

Section: Resultsmentioning

confidence: 99%

PINTnet: construction of condition-specific pathway interaction network by computing shortest paths on weighted PPI

Moon

Lim

et al. 2017

BMC Syst Biol

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BackgroundIdentifying perturbed pathways in a given condition is crucial in understanding biological phenomena. In addition to identifying perturbed pathways individually, pathway analysis should consider interactions among pathways. Currently available pathway interaction prediction methods are based on the existence of overlapping genes between pathways, protein-protein interaction (PPI) or functional similarities. However, these approaches just consider the pathways as a set of genes, thus they do not take account of topological features. In addition, most of the existing approaches do not handle the explicit gene expression quantity information that is routinely measured by RNA-sequecing.ResultsTo overcome these technical issues, we developed a new pathway interaction network construction method using PPI, closeness centrality and shortest paths. We tested our approach on three different high-throughput RNA-seq data sets: pregnant mice data to reveal the role of serotonin on beta cell mass, bone-metastatic breast cancer data and autoimmune thyroiditis data to study the role of IFN- α. Our approach successfully identified the pathways reported in the original papers. For the pathways that are not directly mentioned in the original papers, we were able to find evidences of pathway interactions by the literature search. Our method outperformed two existing approaches, overlapping gene-based approach (OGB) and protein-protein interaction-based approach (PB), in experiments with the three data sets.ConclusionOur results show that PINTnet successfully identified condition-specific perturbed pathways and the interactions between the pathways. We believe that our method will be very useful in characterizing biological mechanisms at the pathway level. PINTnet is available at http://biohealth.snu.ac.kr/software/PINTnet/.

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Thyroid autoimmunity as a window to autoimmunity: An explanation for sex differences in the prevalence of thyroid autoimmunity

Cited by 58 publications

References 66 publications

Increased leptin levels correlate with thyroid autoantibodies in nonobese males

Increased leptin levels correlate with thyroid autoantibodies in nonobese males

Long-term follow-up in primary Sjögren’s syndrome reveals differences in clinical presentation between female and male patients

PINTnet: construction of condition-specific pathway interaction network by computing shortest paths on weighted PPI

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