Presence or severity of Hashimoto's thyroiditis does not influence basal calcitonin levels: observations from CROHT biobank.

PURPOSE: The influence of Hashimoto's thyroiditis (HT) on calcitonin (Ct) production is unresolved question. The aim of this study was to explore if basal Ct levels are influenced by the presence/severity of HT or correlated with clinical phenotypes of HT patients. METHODS: We included 467 HT patients and 184 control participants, from Croatian Biobank of HT patients (CROHT), in this retrospective study. Calcitonin levels between HT patients and controls were compared using Mann-Whitney test. Ct levels between two subgroups of HT patients, divided by intake of levothyroxine (LT4) therapy, were additionally tested to take into account the illness severity. Spearman rank correlation test was used to analyze correlations between Ct levels and 14 relevant phenotypes. RESULTS: We have not detected significant differences in median Ct levels between HT patients and controls (2.2 vs 2.35 pg/mL, respectively, P = 0.717) nor in-between two subgroups of HT patients (P = 0.347). We have not detected statistically significant correlations between Ct levels and clinical phenotypes, although we identified three weak nominal correlations: negative correlation of Ct with TgAb in all HT patients (r = - 0.1, P = 0.04); negative correlation of Ct with age in subgroup of HT patients without LT4 therapy (r = - 0.13, P = 0.04); positive correlation of Ct with BSA in subgroup of HT patients on LT4 therapy (r = 0.16, P = 0.042). CONCLUSION: Our results suggest that HT patients of all disease stages preserve Ct production as healthy individuals and there is no need for Ct measurements in the absence of a nodule. Additional confirmation and clarification of observed nominal correlations are needed due to potential clinical relevance of TgAb and age-dependent Ct decrease in HT women.

High prevalence of thyroid hormone autoantibody and low rate of thyroid hormone detection interference.

OBJECTIVE: Thyroid hormone autoantibody (THAb) is a common antibody in autoimmune disease and can interfere with the detection of thyroid hormone (TH). There was no research reporting the prevalence of THAb in Chinese and the rate of THAb interfering with TH detection. METHODS: We collected 114 patients with autoimmune thyroid disease (AITD) (Hashimoto's thyroiditis, 57 cases; Graves' disease, 57 cases), 106 patients with nonthyroid autoimmune diseases (NTAID), and 120 healthy subjects. According to the presence or absence of thyroid antibodies, patients with NTAID were divided into two groups: NTAID-AITD and NTAID groups. Radioimmunoprecipitation technique was used to detect THAb in all subjects. TH was detected on Abbot and Roche platforms in patients with positive THAb. RESULTS: The prevalence of THAb was 22.8% in Hashimoto's thyroiditis and 45.6% in Graves' disease. The prevalence of THAb in AITD group was lower than that in NTAID or NTAID-AITD groups (34.2% vs. 61.5%, p = 0.014; 34.2% vs. 71.3%, p < 0.01). Among total 98 patients with positive THAb, TH levels of 9 patients were falsely elevated (9.18%). CONCLUSION: The prevalence of THAb in AITD patients was lower than that in NTAID patients. Although THAb had a high frequency in various autoimmune diseases, the prevalence of THAb interfering with TH detection was only 9.18%.

Nuclear Receptors, Ligands and the Mammalian B Cell.

Questions concerning the influences of nuclear receptors and their ligands on mammalian B cells are vast in number. Here, we briefly review the effects of nuclear receptor ligands, including estrogen and vitamins, on immunoglobulin production and protection from infectious diseases. We describe nuclear receptor interactions with the B cell genome and the potential mechanisms of gene regulation. Attention to the nuclear receptor/ligand regulation of B cell function may help optimize B cell responses, improve pathogen clearance, and prevent damaging responses toward inert- and self-antigens.

Rapid cycling bipolar disorder is associated with antithyroid antibodies, instead of thyroid dysfunction.

BACKGROUND: Conclusions regarding the association between antithyroid antibodies or thyroid dysfunction and rapid cycling bipolar disorder (RCBD) have been conflicting. Previous studies suggest that the impact of antithyroid antibodies on mental wellbeing seems to be independent of thyroid function. Here, we investigated their independent association with RCBD in a large, well-defined population of bipolar disorder (BD). METHODS: Fast serum levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid Stimulating Hormone (TSH), TPO-abs and Tg-abs were simultaneously measured in 352 patients with BD. Clinical features of BD were collected through semi-structural interview conducted by trained interviewers with background of psychiatric education. RESULTS: Neither hypothyroidism nor hyperthyroidism was significantly associated with RCBD. Both TPO-abs and Tg-abs were significantly related to RCBD, even after controlling for gender, age, marriage status, education, antidepressants treatment, comorbidity of thyroid diseases, and thyroid function (serum levels of FT3, FT4 and TSH). Although TPO-abs and Tg-abs were highly correlated with each other, binary logistic regression with forward LR selected TPO-abs, instead of Tg-abs, to be associated with RCBD. TPO-abs was significantly, independently of Tg-abs, associated with hyperthyroidism, while Tg-abs was marginally significantly related to hypothyroidism at the presence of TPO-abs. CONCLUSION: TPO-abs might be treated as a biomarker of RCBD. Further exploring the underlying mechanism might help understand the nature of RCBD and find out new treatment target for it.

Integrin αvß3 acting as membrane receptor for thyroid hormones mediates angiogenesis in malignant T cells.

The interaction of lymphoid tumor cells with components of the extracellular matrix via integrin αvß3 allows tumor survival and growth. This integrin was demonstrated to be the membrane receptor for thyroid hormones (THs) in several tissues. We found that THs, acting as soluble integrin αvß3 ligands, activated growth-related signaling pathways in T-cell lymphomas (TCLs). Specifically, TH-activated αvß3 integrin signaling promoted TCL proliferation and angiogenesis, in part, via the upregulation of vascular endothelial growth factor (VEGF). Consequently, genetic or pharmacologic inhibition of integrin αvß3 decreased VEGF production and induced TCL cell death in vitro and in human xenograft models. In sum, we show that integrin αvß3 transduces prosurvival signals into TCL nuclei, suggesting a novel mechanism for the endocrine modulation of TCL pathophysiology. Targeting this mechanism could constitute an effective and potentially low-toxicity chemotherapy-free treatment of TCL patients.

Correlation of thyroid antibodies with TSH, T3 and T4 hormones in patients diagnosed with autoimmune thyroid disorders.

The serum concentrations of anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) antibodies are directly correlate in the induction and diagnosis of autoimmune thyroid disorders (AITDs). Therefore, the evaluation of serum anti-TPO and anti-TG antibodies in relation to thyroid function test parameters including thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). This evaluation would be helpful in early diagnosis of abnormal thyroid function and associated autoimmune thyroid diseases. In this cross-sectional study, the serum anti-TPO, anti-TG, T3, T4 and TSH levels of 311 suspected patients of autoimmune thyroid disorders and 40 control subjects were evaluated. The data were presented as mean, ± standard deviations of the mean. Pearson correlation and chi-square tests were used to assess the correlation coefficients and significance in the contingency tables. The thyroid function test parameters in normal and AITDs suspected patients were significantly different in correlation to elevated serum levels of anti-TPO antibody. A significant association was detected between female gender and elevated levels of anti-TPO (P value = 0.047). A higher percentage of women showed elevated levels of anti-TG, but it was not statistically significant (P value= 0.107). The findings of the study reveal a strong correlation between thyroid function test and thyroid antibodies levels, elaborating the clinical importance of thyroid antibodies in clinical examination and follow-up of patients with autoimmune thyroid disorders.

High prevalence of circulating autoantibodies against thyroid hormones in vitiligo and correlation with clinical and historical parameters of patients.

BACKGROUND: Autoantibodies against thyroid hormones (THAbs) directed towards triiodothyronine (T3-Ab) and/or thyroxine (T4-Ab) are very rare in the general population. They are increased in some nonthyroidal autoimmune diseases, where they seem to predict autoimmune thyroid disorders (ATDs). So far, their presence in patients with vitiligo has not been evaluated, but it might have a possible predictive role. OBJECTIVES: To assess the prevalence of THAbs in a group of vitiligo patients and to correlate their presence with clinical and historical parameters. METHODS: In total 79 patients with nonsegmental vitiligo and 100 controls were examined. Clinical characteristics of vitiligo and family and personal medical history were evaluated. Antinuclear autoantibodies, thyroid hormones and thyroid autoantibodies were measured. IgM T3-Ab, IgG T3-Ab, IgM T4-Ab and IgG T4-Ab were assayed by a radioimmunoprecipitation technique. Fisher's test, Student's t-test and χ(2)-test were used for statistical analysis. RESULTS: Overall 77 of 79 patients (97%) had at least one type of THAb (11 T3-Ab, 10 T4-Ab, 56 both). In the control group, only one person (1%) had THAbs. In patients with vitiligo, T3-Abs were significantly associated with leucotrichia (IgM+IgG, P = 0.033; IgG, P = 0.039; IgM, P = 0.005) and thyroglobulin autoantibodies (IgM+IgG, P = 0.031; IgG, P = 0.058), while the absence of T3-Ab was related to personal history of cancer (IgM+IgG, P = 0.021; IgG, P = 0.039). T4-Abs were significantly associated with vitiligo activity (IgM+IgG, P < 0.001; IgM, P = 0.037) and duration (IgG, P = 0.013). CONCLUSIONS: The surprisingly high prevalence of THAb in patients with vitiligo and their associations suggest a possible pathogenetic role in the disease and stress the tight link between vitiligo and ATDs. Further evaluation in a larger group of patients and an adequate follow-up are needed to define their potential predictive role.

Association of moyamoya disease with thyroid autoantibodies and thyroid function: a case-control study and meta-analysis.

BACKGROUND AND PURPOSE: Evidence suggests that elevated thyroid function and elevated levels of thyroid autoantibodies are associated with risk of moyamoya disease (MMD). Therefore a meta-analysis of all available evidence was performed, including unpublished data from our own center, in order to assess this association. METHODS: Major literature databases were reviewed without language restrictions to identify studies examining the association between MMD and thyroid function or thyroid autoantibodies. These data were combined with those from our own prospective study. This study involved consecutively recruited patients with MMD and two groups of age-matched control patients: patients with non-MMD stroke and healthy individuals. The groups were compared in terms of serum triiodothyronine (T3), thyroxine (T4), free T4, free T3, thyroid stimulating hormone, anti-thyroperoxidase antibody and anti-thyroglobulin antibody. RESULTS: Our prospective study involved 28 patients with MMD, 28 age-matched patients with non-MMD stroke and 28 age-matched healthy control participants. The results showed an association between risk of MMD and elevated thyroid autoantibodies [odds ratio (OR) 9.00, 95% confidence interval (CI) 1.03-78.94] but not between risk of MMD and elevated thyroid function (OR 5.87, 95% CI 0.64-53.93). Meta-analysis of our data with findings from the literature further supported the association with elevated thyroid autoantibodies (OR 8.77, 95% CI 4.45-17.29) and indicated an association with elevated thyroid function (OR 9.74, 95% CI 2.18-43.49). CONCLUSIONS: Evidence strongly suggests that elevated thyroid autoantibodies and elevated thyroid function are independently associated with MMD. These clinical variables may require regular monitoring in patients with MMD.

Anti-Müllerian hormone concentration as a biomarker of pregnancy success or failure.

OBJECTIVE: This study was conducted to determine serum anti-Müllerian hormone (AMH) concentration influence on pregnancy outcome. STUDY DESIGN: In this study we investigated sixty one infertile women (aged 27 to 44 years) who were diagnosed and treated between 2011 and 2013. We determine ovarian reserve measured by AMH concentration. Patients were divided in three groups according to their serum AMH concentration (<1 ng/ml; 1-2.5 ng/ml; >2.5 ng/ml respectively). We investigated the relationship between clinical pregnancy rate and AMH concentration. In addition, anti-thyroid antibodies (anti-TG and/or anti-TPO) positivity and insulin concentration were correlated with AMH level and pregnancy outcome in the study groups. RESULTS: We found no statistical differences between AMH concentration regarding number of pregnancies (42.3%; 41.1 %; 38.9% respectively in study groups; p>0.05). The miscarriage rate was highest in women with AMH>2.5 ng/mL (27.3%, 0%, 86% respectively in study groups; p>0.05). We found that anti-thyroid positivity is more frequent in women with lower AMH concentration (23.1%; 11.7%; 5.5% respectively; p>0.05) and patients with lower serum AMH had higher serum insulin concentration (p<0.05). CONCLUSIONS: It seems that AMH concentration might not reflect oocyte quality and the chance of pregnancy, but increased AMH concentration may be associated with negative pregnancy outcome. Moreover, it cannot be excluded that presence of anti-thyroid antibodies and increased insulin serum concentration may be connected to diminished ovarian reserve measured by AMH concentration.

The essential role of anti-thyroid antibodies in chronic idiopathic urticaria.

BACKGROUND: An autoimmune etiology has been suggested in up to one-third of cases of chronic idiopathic urticaria (CIU), in which it has been proposed that a subset of cases are associated with thyroid autoimmunity. The objective of our present study was to verify the prevalence of thyroid antibodies in the patients with CIU. METHODS: Sixty patients aged 12-51 years, who met criteria for CIU, and 40 aged-matched healthy controls (18 males and 22 females) were participated in this study. Serum anti-thyroid antibodies (ATAs), thyroid hormones, total immunoglobulin E (IgE), and food allergen-specific IgE antibodies were measured. The CIU group was treated with anti-H1 and anti-H2 histamines for 3 weeks. RESULTS: The total ATA positive rate was 27.3% (33% males and 25% females) in the CIU group. The prevalence of anti-thyroglobulin antibodies, anti-TSH-receptor antibodies, and anti-thyroid peroxidase antibodies were 16.6%, 83.3%, and 8.3%, respectively. The thyroid hormones, T3, and T4, and the TSH were within the normal limits. The radioallergosorbent test was negative for food allergens, and only 18% of the patients had a total IgE concentration >200 IU/mL. CONCLUSION: ATAs were found in 27% of the patients with CIU, but these antibodies did not dysregulate thyroid hormone secretion nor did they mediate any clinical manifestations.

Autosomal-dominant chronic mucocutaneous candidiasis with STAT1-mutation can be complicated with chronic active hepatitis and hypothyroidism.

PURPOSE: To describe a case of autosomal-dominant (AD)-chronic mucocutaneous candidiasis (CMC) with a signal transducer and activator of transcription (STAT) 1 gene mutation, and some of the important complications of this disease such as chronic hepatitis. METHODS: We present a 23-year-old woman with CMC, chronic active hepatitis, and hypothyroidism. Her father also had CMC. We performed several immunological analyses of blood and liver samples, and searched for gene mutations for CMC in the patient and her father. RESULTS: We identified the heterozygous substitution c.821 G > A (p.Arg274Gln) in the STAT1 gene of both the patient and her father. The level of ß-glucan induced interferon (IFN)-γ in her blood cells was significantly low. Immunoblot analysis detected serum anti-interleukin (IL)-17 F autoantibody. She was found to have increased (low-titer) antibodies related to her hypothyroidism and hepatitis. Her serum IL-18 levels fluctuated with her AST and ALT levels. Liver biopsy revealed CD68-positive cell infiltration and IL-18 expression in the sinusoidal regions. These results suggest that the chronic active hepatitis in this patient may be exacerbated by the excessive IL-18 accumulation caused by recurrent mucocutaneous fungal infection, and decreased IFN-γ production. CONCLUSIONS: AD-CMC is known to be caused by a gain-of-function mutation of the STAT1 gene. Chronic active hepatitis is a rare complication of AD-CMC, with currently unknown pathogenesis. It seems that the clinical phenotype in this patient is modified by autoimmune mechanisms and cytokine dysregulation. AD-CMC can be complicated by various immune disorders including autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.

[Determination of serum neopterin levels in patients with autoimmune thyroid diseases]. / Szérumneopterin-szintek vizsgálata autoimmun pajzsmirigybetegekben.

UNLABELLED: An elevated serum level of neopterin indicates the activation of the cellular immune system. AIM: The objective was to find a correlation in autoimmune thyroid patients between neopterin levels and the clinical stage of the disease and to examine whether neopterin can predict the relapse of the disease. METHODS: Serum neopterin, thyroid stimulating hormone, free thyroxine, free triiodothyronine, anti-thyroglobulin and anti-thyroid peroxidase antibody levels were determined in 137 patients with Graves' disease (in different stages), 25 with Hashimoto's thyroiditis and 14 with toxic adenoma. RESULTS: The neopterin levels were significantly higher in patients with Graves' disease (hyper-, eu-, hypothyroidism and relapsed hyperthyroidism) and Hashimoto's thyroiditis. Positive correlation was found between neopterin and anti-thyroglobulin and anti-thyroid peroxidase antibody levels, but no correlation was detected between neopterin levels and thyroid hormones, thyroid stimulating hormone values and antibodies against thyroid stimulating hormone receptors. CONCLUSIONS: Higher level of serum neopterin reflects an underlying autoimmune process, and does not correlate with changes in thyroid hormone levels. Determination of neopterin level can be an important indicator in the exacerbation of autoimmune processes.

Research progress on the role of PKM2 in the immune response.

Pyruvate kinase (PK) is a key enzyme that catalyzes the dephosphorylation of phosphoenolpyruvate (PEP) into pyruvate, and is responsible for the production of ATP during glycolysis. As another important isozyme of PK, pyruvate kinase M2 (PKM2) exists in cells with high levels of nucleic acid synthesis, such as normal proliferating cells (e.g., lymphocytes and intestinal epithelial cells), embryonic cells, adult stem cells, and tumor cells. With further research, PKM2, as an important regulator of cellular pathophysiological activity, has attracted increasing attention in the process of autoimmune response and inflammatory. In this re]view, we examine the contribution of PKM2 to the human immune response. Further studies on the immune mechanisms of PKM2 are expected to provide more new ideas and drug targets for immunotherapy of inflammatory and autoimmune diseases, guiding drug development and disease treatment.

Vitiligo and autoimmunity: an epidemiological study in a representative sample of young Italian males.

BACKGROUND: It is stated that patients with vitiligo have an increased risk of developing autoimmune diseases. OBJECTIVE: The aim of this study was to estimate the prevalence of autoantibodies or overt autoimmune diseases in a group of vitiligo patients examined among a sample deemed to be representative of the general population of young men living in southern Italy. METHODS: A total of 60 vitiligo patients were identified among 34,740 potential conscripts visited to evaluate their fitness to compulsory service in Italian Navy, obtaining a prevalence of 0.17% (95% CI: 0.13-0.22), which was deemed the prevalence of vitiligo in the Italian general population of the same age and sex. Forty of these vitiligo patients underwent blood test including also the search of the main autoantibodies. RESULTS: Circulating autoantibodies were detected in 42.5% of subjects. Anti-thyroglobulin antibodies were documented in 27.5%, anti-thyroperoxidase in 22.5%, anti-smooth muscle in 17.3%, anti-nuclear, anti-mitochondrial and anti-gastric parietal cells in 2.5% respectively. Only in two cases (5%) an overt thyroid disease was diagnosed. No significant association between the extension of the skin involved / clinical course of the disease and circulating autoantibodies was detected. Circulating autoantibodies (particularly anti-thyroid antibodies) were statistically associated with a lower duration of the disease. CONCLUSIONS: In agreement with other studies, autoantibodies in the lack of clinical manifestations have been frequently observed in our vitiligo patients, especially during the early phase of the disease. The clinical significance of this finding seems to be limited, with the possible exception of thyroid disease, and it needs further exploration, through large cohort studies.

PKM2-dependent metabolic skewing of hepatic Th17 cells regulates pathogenesis of non-alcoholic fatty liver disease.

Emerging evidence suggests a key contribution to non-alcoholic fatty liver disease (NAFLD) pathogenesis by Th17 cells. The pathogenic characteristics and mechanisms of hepatic Th17 cells, however, remain unknown. Here, we uncover and characterize a distinct population of inflammatory hepatic CXCR3+Th17 (ihTh17) cells sufficient to exacerbate NAFLD pathogenesis. Hepatic ihTh17 cell accrual was dependent on the liver microenvironment and CXCR3 axis activation. Mechanistically, the pathogenic potential of ihTh17 cells correlated with increased chromatin accessibility, glycolytic output, and concomitant production of IL-17A, IFNγ, and TNFα. Modulation of glycolysis using 2-DG or cell-specific PKM2 deletion was sufficient to reverse ihTh17-centric inflammatory vigor and NAFLD severity. Importantly, ihTh17 cell characteristics, CXCR3 axis activation, and hepatic expression of glycolytic genes were conserved in human NAFLD. Together, our data show that the steatotic liver microenvironment regulates Th17 cell accrual, metabolism, and competence toward an ihTh17 fate. Modulation of these pathways holds potential for development of novel therapeutic strategies for NAFLD.

Effects of glucocorticoid pulse therapy on thyroid function and thyroid antibodies in children with graves' disease.

BACKGROUND: Glucocorticoid treatment is used in children with Graves' disease (GD) only in cases of exophthalmos. The purpose of this study was to observe the effects of glucocorticoid pulse therapy on thyroid function and thyroid antibodies in children with GD. METHODS: Twenty children who were treated by intravenous methylprednisolone pulse therapy (MPT) followed by oral prednisolone administration and antithyroid drugs were included in the pulse group. Twenty children who were treated with antithyroid drugs alone were included in the control group. Serum concentrations of free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), and thyrotropin receptor antibodies (TRAb) were recorded at baseline and 10 days, 30 days, and 60 days after treatment. RESULTS: Significant differences in FT3, FT4, TSH, TPOAb, TGAb, and TRAb levels were found in the pulse group and the control group from baseline to follow-up time points (all p < 0.05). On the 30th day, the TRAb level in the pulse group was significantly lower than that in the control group (p = 0.023). However, the level of TRAb rose on the 60th day. For values of TRAb at baseline, 10 days, and 60 days after treatment, there were no significant differences respectively between the pulse group and the control group (all p > 0.05). No significant differences were observed in FT3, FT4, TSH, TPOAb, and TGAb levels between the pulse group and the control group (all p > 0.05). CONCLUSIONS: The results suggested that the effect of intravenous MPT followed by oral prednisolone on TRAb level was temporary in children with GD. Glucocorticoid pulse therapy was not beneficial for the sustained recovery of thyroid function.

Experimental study on abnormal thyroid function in patients with Hashimoto's thyroiditis caused by interference of thyroid hormone autoantibodies.

INTRODUCTION: Thyroid hormone autoantibody (THAAb) is one of the important factors affecting thyroid function measurement. By analyzing the examination of a patient suffered with Hashimoto's thyroiditis, we sought to find a correct assessment method. MATERIAL AND METHODS: Radioimmunoassay, chemiluminescence immunoassay on an ADVIA Centaur XP system and Architect i2000sr platform, and electrochemiluminescence immunoassay on a Roche Cobas 601 system were used for detecting thyroid function. Polyethylene glycol (PEG) precipitation were performed to eliminate the influence of THAAbs. RESULTS: The results showed that the patient's thyroid function was consistent with the clinical manifestations and conformed to the law of the hypothalamic-pituitary-thyroid axis at Architect-i2000sr platform and Roche-Cobas-601 system. The content of FT4 was significantly reduced and lower than the normal reference range, after the patients' serum was treated with PEG, which was in line with the clinical practice. The serum THAAb titer of the patients was nearly 100 times higher than that of the control group. CONCLUSIONS: Considering an abnormal thyroid function examination, it is necessary for laboratory staff to retest samples on different platforms. It is of great significance to provide a true and accurate result to clinicians and patients.

The Association of TSH and Thyroid Hormones With Lymphopenia in Bacterial Sepsis and COVID-19.

CONTEXT: Lymphopenia is a key feature of immune dysfunction in patients with bacterial sepsis and coronavirus disease 2019 (COVID-19) and is associated with poor clinical outcomes, but the cause is largely unknown. Severely ill patients may present with thyroid function abnormalities, so-called nonthyroidal illness syndrome, and several studies have linked thyrotropin (thyroid stimulating hormone, TSH) and the thyroid hormones thyroxine (T4) and 3,5,3'-triiodothyronine (T3) to homeostatic regulation and function of lymphocyte populations. OBJECTIVE: This work aimed to test the hypothesis that abnormal thyroid function correlates with lymphopenia in patients with severe infections. METHODS: A retrospective analysis of absolute lymphocyte counts, circulating TSH, T4, free T4 (FT4), T3, albumin, and inflammatory biomarkers was performed in 2 independent hospitalized study populations: bacterial sepsis (n = 224) and COVID-19 patients (n = 161). A subgroup analysis was performed in patients with severe lymphopenia and normal lymphocyte counts. RESULTS: Only T3 significantly correlated (ρ = 0.252) with lymphocyte counts in patients with bacterial sepsis, and lower concentrations were found in severe lymphopenic compared to nonlymphopenic patients (n = 56 per group). Severe lymphopenic COVID-19 patients (n = 17) showed significantly lower plasma concentrations of TSH, T4, FT4, and T3 compared to patients without lymphopenia (n = 18), and demonstrated significantly increased values of the inflammatory markers interleukin-6, C-reactive protein, and ferritin. Remarkably, after 1 week of follow-up, the majority (12 of 15) of COVID-19 patients showed quantitative recovery of their lymphocyte numbers, whereas TSH and thyroid hormones remained mainly disturbed. CONCLUSION: Abnormal thyroid function correlates with lymphopenia in patients with severe infections, like bacterial sepsis and COVID-19, but future studies need to establish whether a causal relationship is involved.

Isovitexin potentiated the antitumor activity of cisplatin by inhibiting the glucose metabolism of lung cancer cells and reduced cisplatin-induced immunotoxicity in mice.

The increased resistance and toxicity have become the main causes of chemotherapy failure for treating lung cancer. The combination of chemotherapeutic drugs with other agents has been recognized as a promising strategy to overcome these difficulties. Isovitexin (IVT) is a well-known flavone C-glycoside found in many plants and has attracted wide attention due to its obvious antitumor and antioxidant effects. In this study, we investigated the synergistic effects of IVX and cisplatin (DDP) in non-small cell lung cancer (NSCLC) A549 and H1975 cells. The results showed that the combined treatment with IVT and DDP markedly inhibited proliferation and induced apoptosis of the two NSCLC cells. Using a mouse model of A549 xenograft, IVT potentiated the inhibition of DDP on tumor growth, but reduced DDP-induced hepatotoxicity and nephrotoxicity in mice. Remarkedly, IVT promoted lipopolysaccharide (LPS)- and lectin- stimulated splenocyte proliferation, and enhance cytotoxic T lymphocyte (CTL) and natural killer (NK) cell activities as well as the production of IL-2 and TNF-α. Furthermore, IVT significantly reduced glucose uptake, lactate production, and ATP production, and downregulated the protein expressions of pyruvate kinase M2 (PKM2)-mediated pathway in both A549 and H1975 cells. After the over-expression of PKM2 in the NSCLC cells, the synergistic antitumor effect of IVT and DDP was markedly weakened. Therefore, IVT not only inhibited cell proliferation and glucose metabolism via downregulating the expression of PKM2 to enhance the antitumor activity of DDP against lung cancer cells, and improved DDP-induced immunotoxicity in mice. It also presented a novel strategy to enhance the anti-tumor effect of platinum-based chemotherapy against NSCLC.

Thyroid Hormone and Deiodination in Innate Immune Cells.

Thyroid hormone has recently been recognized as an important determinant of innate immune cell function. Highly specialized cells of the innate immune system, including neutrophils, monocytes/macrophages, and dendritic cells, are capable of identifying pathogens and initiating an inflammatory response. They can either phagocytose and kill microbes, or recruit other innate or adaptive immune cells to the site of inflammation. Innate immune cells derive from the hematopoietic lineage and are generated in the bone marrow, from where they can be recruited into the blood and tissues in the case of infection. The link between the immune and endocrine systems is increasingly well established, and recent studies have shown that innate immune cells can be seen as important thyroid hormone target cells. Tight regulation of cellular thyroid hormone availability and action is performed by thyroid hormone transporters, receptors, and the deiodinase enzymes. Innate immune cells express all these molecular elements of intracellular thyroid hormone metabolism. Interestingly, there is recent evidence for a causal relationship between cellular thyroid hormone status and innate immune cell function. This review describes the effects of modulation of intracellular thyroid hormone metabolism on innate immune cell function, specifically neutrophils, macrophages, and dendritic cells, with a special focus on the deiodinase enzymes. Although there are insufficient data at this stage for conclusions on the clinical relevance of these findings, thyroid hormone metabolism may partially determine the innate immune response and, by inference, the clinical susceptibility to infections.