Search Results (114)

The incidence of Hashimoto’s disease (HD) increases with age and in people who have other autoimmune diseases. It is characterized by lymphocytic infiltration, fibrosis, and atrophy of the thyroid parenchyma with the simultaneous presence of thyroid peroxidase antibodies (ATPO) and/or thyroglobulin antibodies (ATG). Eicosanoids are formed via the cyclooxygenase (COX), lipoxygenase (LOX), and monooxygenase (CYP450) pathways with arachidonic acid (ARA), resulting in the production of epoxyeicosatrienoic acids (EETs) or hydroxyeicosatetraenoic acids (HETEs). These eicosanoids can act in an autocrine or paracrine manner on target cells. This study aimed to examine whether a gluten-free diet (GFD) can modulate the enzymatic pathways of the pro-inflammatory ARA cascade. The study material consisted of serum samples from Caucasian female patients with HD aged 18–55 years. Participants were enrolled in the study based on the presence of an ultrasound characteristic of HD, and elevated serum levels of anti-thyroid peroxidase antibodies and anti-thyroglobulin antibodies. Patients with confirmed celiac disease did not participate in the study. A total of 78 samples were analyzed, with 39 collected after 3 months of following a GFD. Eicosanoids (thromboxane B2, prostaglandin E2, leukotriene B4, and 16R-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid (16-RS HETE)) were extracted using high-performance liquid chromatography. The contribution of leukotriene (LTB) was analyzed in the LOX pathway, prostaglandins (PGE2) and thromboxane (TXB2) were selected for the involvement of the COX pathway, and 16RS HETE was used for the CYP450 pathway. All parameters were analyzed before and after a 3-month dietary intervention that included a gluten-free diet. In the obtained results, only one mediator, leukotriene B4, was significant (p < 0.05). The mean level on the initial visit was 0.202 ± 0.11 (SD), while it was 0.421 ± 0.27 (SD) on the subsequent visit, indicating a significant increase in its level after implementing a GFD. Although there was a trend in the CYP 450 pathway of decreased 16-RS HETE, the presented correlations show that thromboxane B4 and 16RS-HETE were positively correlated with the body mass and body fat mass of the examined patients. There was a trend in the CYP 450 pathway of decreased 16-RS HETE after GFD. Thromboxane B4 and 16RS-HETE levels before GFD were positively correlated with the body mass and body fat mass of the examined patients. A gluten-free diet in HD does not suppress the synthetic pathways of LOX, COX, or cytochrome P450 (CYP450). The level of adipose tissue has a greater impact on the inflammatory processes in HD than a gluten-free diet. This study does not confirm the suppressive effect of a gluten-free diet on the pro-inflammatory arachidonic acid cascade in any of the three analyzed mediator synthesis LOX, COX, CYP450 pathways. Full article

Background: Hashimoto’s thyroiditis (HT), the most prevalent autoimmune thyroid disorder in reproductive-age women, has been linked to diminished ovarian reserve and subfertility. This study aimed to evaluate the relationship between HT and key fertility parameters, including hormonal markers and reproductive outcomes, while also exploring the potential impact of thyroid hormone replacement therapy. Methods: A retrospective observational study was conducted on 86 women undergoing fertility evaluation. Participants were divided into two groups based on anti-thyroid peroxidase antibodies (ATPO): the HT group (n = 49) and the control group (n = 37). Among women with HT, 57% were receiving levothyroxine (Euthyrox^®) at the time of assessment. Variables analyzed included serum levels of anti-Müllerian hormone (AMH), thyroid-stimulating hormone (TSH), insulin resistance index (HOMA-IR), number of oocytes retrieved, blastocysts formed, pregnancies achieved, and live births. Statistical methods included t-tests, Mann–Whitney U tests, Pearson/Spearman correlations, and linear regression models. Results: Women in the HT group had slightly lower AMH levels and oocyte counts compared to controls, though these differences did not reach statistical significance. TSH values were higher in the HT group and showed a significant negative correlation with blastocyst formation (p = 0.03). Although TSH also showed negative trends with oocyte count, pregnancies, and live births, these correlations did not reach statistical significance. A post-hoc subgroup analysis revealed that HT patients receiving levothyroxine tended to have higher numbers of oocytes retrieved and blastocysts formed compared to untreated HT patients, suggesting a possible beneficial effect of thyroid hormone replacement, although the differences were not statistically significant. Conclusions: HT is associated with subtle but clinically relevant impairments in ovarian reserve and reproductive potential. Thyroid hormone replacement may offer modest benefits and should be considered in the individualized management of fertility in women with thyroid autoimmunity. Full article

Hashimoto’s thyroiditis is the most prevalent autoimmune thyroid disorder, and it disproportionately affects women of reproductive age. Its impact on fertility and assisted reproductive technologies [ART] has become an area of growing clinical interest. Thyroid autoimmunity can influence female reproductive health through multiple interconnected mechanisms, including subtle thyroid hormone imbalances, reduced ovarian reserve, altered endometrial receptivity, and dysregulated immune responses. Subclinical hypothyroidism and the presence of anti-thyroid antibodies have been linked to increased miscarriage risk and reduced success rates in ART, particularly in intracytoplasmic sperm injection (ICSI) cycles. Although levothyroxine supplementation is widely used, its benefits in euthyroid women remain uncertain. Recent studies suggest that gut microbiota may modulate immune function and affect fertility outcomes among women with autoimmune thyroid conditions. This narrative review synthesizes findings from a broad literature base of over 40 peer-reviewed publications published between 2010 and 2025, with 30 of the most relevant and methodologically robust studies selected for detailed analysis. The review integrates clinical, endocrine, immunological, and microbiome-related perspectives. The evidence supports the need for personalized fertility management in women with Hashimoto’s thyroiditis and highlights directions for future research into immune and microbiota-targeted therapies. Full article

A previous cross-sectional study found impaired health-related quality of life (HRQoL) in hyperthyroid cats, but the longitudinal impact of treatment—especially differences between radioiodine (RAIT) and antithyroid drug (ATD) approaches—remains unclear. This study aimed to evaluate changes in HRQoL in recently diagnosed (<6 months) hyperthyroid cats that underwent RAIT or received ATD. HRQoL was assessed using the validated HyperthyroidismQoL-cat questionnaire at baseline and after 1, 3, and 6 months, alongside thyroid status (eu-/hypo-/hyperthyroid) evaluation. Mixed-effects model analysed the influence of treatment type, timepoint, and thyroid status on log(HRQoL). HRQoL differences between groups at baseline and comparison to a non-hyperthyroid control group (n = 322) from a previous study at month 6 were examined using Mann–Whitney U tests. Data are presented as median (range), with significance set at p < 0.05. Thirty-eight client-owned hyperthyroid cats (15 ATD, 23 RAIT) were included. HRQoL scores at baseline did not differ between groups (RAIT: 103.5 [27–211], ATD: 73 [22–260], p = 0.22). HRQoL significantly improved over time (p < 0.001) but was not affected by treatment type (p = 0.20) or thyroid status (p = 0.40). Despite improvement, HRQoL remained lower than in non-hyperthyroid controls (hyperthyroid: 42.5 [3–161.5], non-hyperthyroid: 27 [0–249], p = 0.007). This study highlights the overall positive impact of treatment on HRQoL, but due to the lack of randomisation and heterogeneity of subjects and treatment, conclusion have to be considered preliminary. Full article

Objectives: Iodine and selenium are key elements for thyroid. There is also evidence of their immunoregulatory potential. However, the current state of knowledge of potential interactions among iodine—selenium—thyroid—immune system is not sufficient. The aim of the study was to evaluate iodine and selenium statuses and examine the relationship between them and the functioning of the thyroid and immune system in a group of women of reproductive age, without previously diagnosed disease. Methods: The study involved a group of 60 women aged 19–40 from southern Poland. The concentrations of iodine and selenium were determined in serum samples using the ICP-MS and AAS methods, respectively. Thyroid function was assessed by determining serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), and anti-thyroid peroxidase antibodies (anti-TPO) by electrochemiluminescence methods. Glutathione peroxidase 3 (GPX3) and ferric ion reducing antioxidant power (FRAP) in serum were measured by spectrophotometric methods. Immune functions were evaluated by analyzing cytokine levels using ELISA tests, including interferon-γ, interleukin-4, interleukin-17, and transforming growth factor-β. Results: No significant correlations between selenium and thyroid or immunological parameters were observed. The level of iodine in serum positively correlated with free thyroxine, indicating its importance for maintaining normal thyroid function, as well as with FRAP in serum, suggesting a protective role of iodine-mediated antioxidant activity on thyroid function. Conclusions: Our results underline the complexity of the system of correlations between iodine–selenium–thyroid–immune function. Nevertheless, understanding them may turn out to be crucial for developing preventive and therapeutic strategies in the context of thyroid diseases. Full article

Background: Thyroid autoimmunity (TAI) has been widely associated with reduced fertility; however, its impact on assisted reproductive technology (ART) outcomes in euthyroid women remains controversial. Ovarian reserve (OR) and anti-Müllerian hormone (AMH) are considered to be the most reliable predictors of controlled ovarian hyperstimulation (COH) and ART outcome. This study aims to evaluate whether TAI affects COH outcomes depending on the OR, or if TAI is an independent negative factor affecting COH outcomes. Methods: This study includes 341 infertile euthyroid participants under 38 years old undergoing ART at a single reproductive medicine center. The serum concentrations of sex hormones, thyrotropin (TSH), AMH, and antithyroid antibodies (ATAbs) were measured before COH. Ovarian response to COH, assessed by oocyte number and maturation (percentage of mature MII oocytes), fertilization rate (FR), and early embryo development (cleavage and blastocyst rate), were assessed in 191 participants with TAI and 150 TAI negative age-matched controls with normal ORs. The TAI group was further divided into two subgroups: the TAI1 group with normal OR (n = 120) and the TAI2 group with diminished ORs (n = 71). Results: The mean of the retrieved oocytes was significantly lower in TAI1 (p = 0.015) and expectedly significantly lower in TAI2 (p < 0.001) compared to the control. The percentage of MII oocytes was significantly lower in the TAI1 (p < 0.001) and TAI2 (p = 0.009) groups compared to the control group. We observed significantly lower FR (p = 0.002), cleavage rate (p = 0.020), and blastocyst rate (p < 0.001) in the TAI1 group compared to control. In the TAI2 group, there was a lower cleavage rate (p < 0.001) and blastocyst rate (p < 0.001) compared to the control. There was no difference in the mean percentage of MII oocytes, FR, and cleavage rate between the TAI1 and TAI2 groups, but the blastocyst rate was significantly lower (p < 0.001) in the TAI2 group. Conclusions: TAI may represent a negative predictor of in vitro fertilization outcomes by impairing oocyte maturation, fertilization rate, and embryo development in ART cycles, regardless of ORs. Full article

Radioiodine (RAI) treatment (RAIT) is considered the gold standard for treatment of feline hyperthyroidism. This study aimed to assess owners’ motivation, concerns and satisfaction with RAIT and health-related quality of life (HRQoL) changes in RAI-treated cats. Two surveys (before and six months post-RAIT) were sent to owners of cats scheduled for RAIT between April 2023 and March 2024. The owners of 78 and 68 cats completed the first and the second surveys, respectively. The main reasons for choosing RAIT were that RAIT was considered the gold standard treatment (n = 27/78; 35%) and difficulties administering antithyroid drugs (n = 18/78; 23%). The primary care veterinarian (n = 50/78; 64%) and the internet (n = 33/78; 42%) were the main information sources about RAIT at the referral clinic. Owners were mostly concerned about the anaesthetic risk and hospitalisation, with the cat missing the owner and vice versa being the main worries. Most owners were satisfied with the outcome and their decision for RAIT. The HRQoL score improved within the first six months after RAIT (p < 0.01), with no difference between euthyroid and hypothyroid cats (p = 0.609). This study emphasises the role of the primary care veterinarian and the internet as primary sources of information regarding RAIT. The findings help to better understand owner concerns, improve owner counselling, and educate primary care veterinarians about RAIT. Full article

Objectives: The aim of this study was to find correlations between vitamin D deficiency and thyroid autoimmune pathology in a group of patients from Dobrogea, a non-endemic geographical area, with a high degree of sunshine. An important factor in maintaining immunological balance is the intake of an adequate level of vitamin D. Multiple studies have suggested that vitamin D deficiency is associated with a higher incidence of autoimmune diseases. Recent studies have analyzed the possible effect of this factor in promoting autoimmunity, as the serum level of BAFF often increases among patients with systemic autoimmune diseases. Methods: This study included 80 patients with autoimmune thyroid pathology from the Dobrogea area. The entire study group (n = 80) was divided according to the established diagnosis into two study groups: Group 1 included 62 patients with CAT (chronic autoimmune thyroiditis), and Group 2 included 18 patients with GD (Graves’ disease). Results: Vitamin D study average values of 25-OH-vitamin D found statistically significant differences between vitamin D values in the two groups (p = 0.018). Determination of BAFF (B-cell-activating factor) serum levels among patients with CAT and GD obtained a lower mean value of BAFF for the CAT group compared with the GD group. The evolution of BAFF serum level related to the serum levels of the antithyroid antibodies ATPO (antithyroidperoxidase) and ATG (antithyroglobulin) was also analyzed. In the patients with GD, BAFF was not correlated with the value of ATPO or ATG, but in the patients with CAT, a correlation was found between the value of BAFF and the level of ATG but not the ATPO level. Conclusions: This study analyzed BAFF serum levels in patients with CAT and GD. The results indicate that BAFF acts as a stimulatory factor of immunoglobulin production in autoimmune diseases. These results require clarifying the role and therapeutic benefits of supplementing vitamin D intake in patients with autoimmune diseases. Full article

Background/Objectives: Hashimoto’s thyroiditis (HT) is an autoimmune disease influenced by genetic factors and environmental triggers that affect immune system function. Data suggest that vitamin D may also play a role in the etiopathogenesis of HT. Methods: This retrospective study included patients admitted to the Endocrinology and Metabolic Diseases Outpatient Clinic. Data from individuals aged 18 years and older were analyzed, including serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG), and vitamin D. HT was diagnosed based on the presence of anti-TPO and/or anti-TG antibodies, while individuals with negative results for both were classified as non-HT. Thyroid function was categorized as euthyroid if TSH levels were between 0.55 mU/L and 4.78 mU/L and fT4 levels were between 0.89 ng/dL and 1.76 ng/dL; hypothyroid status was defined as TSH > 4.78 mU/L. Vitamin D levels were classified as deficient (<50 nmol/L), insufficient (50–74.9 nmol/L), or sufficient (≥75 nmol/L). Results: Of the total participants, 25,018 did not have HT, while 27,800 were diagnosed with HT. Vitamin D level was significantly higher in the HT group than the non-HT group (41.43 nmol/L and 39.44 nmol/L, p < 0.001). Vitamin D deficiency was present in 65.5% of the non-HT group and 62.1% of the HT group (p < 0.001). Subgroup analyses based on thyroid function showed that vitamin D levels were highest in the euthyroid HT group and similar in the euthyroid non-HT, hypothyroid non-HT, and hypothyroid HT groups (p < 0.001). Conclusions: In conclusion, while vitamin D levels were higher in the HT group compared to the non-HT group, no clinically significant association between vitamin D levels and HT or autoantibody positivity was observed. Vitamin D deficiency was more prevalent in the hypothyroid group compared to the euthyroid group. This study suggests that although vitamin D deficiency may not be directly involved in the pathogenesis of HT, it may still play a role in modulating immune activity or influencing the disease phenotype.. Full article

Turner syndrome (TS) is a genetic disorder caused by abnormalities in one of the X chromosomes. Individuals with TS have a higher incidence of autoimmune thyroid disorders, particularly Hashimoto’s disease, leading to thyroid dysfunction, most commonly hypothyroidism. Hormonal imbalance, growth hormone deficiency, and reduced physical activity contribute to muscle weakness in TS patients, and thyroid dysfunction can exacerbate these effects. The purpose of this study was to evaluate whether thyroid factors affect muscle strength in female patients with TS. The study included 70 women with TS and 88 age- and weight-matched controls. TS diagnoses were genetically confirmed (mosaic karyotypes: n = 20; monosomy X: n = 37; structural abnormalities: n = 7). The main criterion for exclusion from the study was unbalanced thyroid function. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and thyroid antibodies (anti-thyroid peroxidase antibodies (aTPO), anti-thyroglobulin antibodies (aTG)) were measured, and muscle strength was assessed using hand-held dynamometry. In TS patients, higher TSH levels were positively correlated, and higher fT4 levels were negatively correlated with muscle strength. No such correlations were found in controls. Thyroid compensation may impact musculoskeletal health in TS. Lower-normal TSH levels are associated with reduced muscle strength, and autoimmune thyroid changes like aTPO and aTG may contribute to muscle deterioration. Further research is needed to confirm these findings. Full article

Background: The exhalation of radioiodine following radioiodine therapy (RIT) presents a challenge in radiation protection, though the mechanisms remain incompletely understood. Previous studies have indicated that radioiodine is predominantly exhaled in an organically bound form in humans. Methods: This study investigates the chemical composition and exhaled amounts of radioiodine, as well as the impact of thyroid-targeted pharmacological interventions, using a controlled mouse model. Female Balb/c mice (25 g) were administered oral doses of radioiodine (0.1, 1, 2, 10, and 23 MBq per animal) with and without prior treatment using thyroid-blocking agents (stable iodine, perchlorate) or antithyroid drugs (carbimazole). Exhaled radioiodine was collected in metabolic cages, separating chemical forms (aerosolized iodine, elemental iodine, organically bound iodine), and quantified via scintillation counter. Results: The exhaled radioiodine activity was proportional to the administered dose (0.2–0.3%). Thyroid-blocking agents increased exhalation, shifting toward elemental iodine. Antithyroid drugs reduced exhalation but increased aerosol formation, particularly at higher I-131 doses. Organically bound iodine remained the predominant exhaled species in all groups. Conclusions: These results highlight the critical role of the thyroid in radioiodine organification. The blockade of thyroid uptake disrupted the formation of organically bound iodine, suggesting that iodine organification requires passage through the thyroid. Additionally, the results support the hypothesis that iodine metabolism outside the thyroid is less efficient, contributing to the formation of organic iodine species. Radical formation is likely a key factor in generating these volatile iodine species, with radiation-induced iodine and methyl radicals playing a role in their formation. Full article

Current therapies for Graves’ disease (GD) primarily aim to manage hyperthyroidism through synthetic antithyroid drugs, radioiodine, or surgery. However, these approaches are often limited by their incomplete efficacy and the risk of inducing hypothyroidism. The latest advances in understanding the autoimmune mechanisms driving GD have paved the way for novel therapies targeting the thyrotropin receptor (TSH-R) or immune pathways. Overall, key targets include cluster of differentiation 20 (CD20), cluster of differentiation 40 (CD40), protein tyrosine phosphatase non-receptor type 22 (PTPN22), cytotoxic T lymphocyte antigen-4 (CTLA-4), B cell-activating factor (BAFF), and the Fc receptor-like protein 3 (FcRL3). Recent preclinical studies and clinical trials testing targeted therapies have shown promising results in terms of efficacy and safety. Here, we present a narrative review of the literature on emerging therapeutic approaches for GD that are currently under investigation. Full article

Background/Objectives: Chronic spontaneous urticaria (CSU) is an immune-mediated skin disorder, with increasing evidence suggesting its association with autoimmune thyroid diseases. The presence of antithyroid antibodies (anti-TPO and anti-TG) and autoimmune thyroid disease indicates shared immunological mechanisms in the pathogenesis of both conditions. This study examines the prevalence of autoimmune thyroid changes in patients with CSU. Methods: The study was conducted as a combined retrospective-prospective observational analysis. It included 43 patients with CSU and 50 healthy participants in the control group. Thyroid hormone levels (TSH, T3, T4), anti-TPO and anti-TG antibodies, as well as ultrasound characteristics of the thyroid gland, were analyzed. Results: In patients with CSU, a higher prevalence of hypothyroidism (27.9% vs. 4% in the control group), hypertension, asthma, and diabetes were observed. Elevated levels of anti-TPO antibodies were found in 51.2% of CSU patients, compared to only 6% in the control group (p < 0.001). Similarly, anti-TG antibodies were increased in 41.9% of CSU patients, compared to 4% in the control group. Additionally, ultrasound analysis revealed significant differences in thyroid morphology, with a heterogeneous structure observed in 72.1% of CSU patients, compared to only 14% in the control group (p < 0.001). Nodular changes were present in 34.88% of CSU patients, whereas the prevalence in the control group was only 6% (p < 0.001). Conclusions: Our results confirm a significant association between CSU and autoimmune thyroid diseases, including a high prevalence of anti-TPO and anti-TG antibodies, hypothyroidism, diffuse heterogeneity, and nodular changes. Additionally, elevated T3 hormone levels were common among CSU patients, while T4 levels did not differ significantly from those in the control group. Full article

Graves’ disease and hyperthyroidism in women with childbearing potential are a challenge in pre-conceptional counseling. The non-surgical alternatives are radioiodine therapy or antithyroid drugs. Here, we focus on the TSH receptor antibody (TRAb) level—without or after radioiodine therapy—and the probability of fetal or neonatal hyperthyroidism. This immunological effect should be weighed against the risk of congenital malformation taking propylthiouracil during pregnancy. For up to 2 years after radioiodine therapy for Graves’ disease, TRAb levels may remain above the pre-therapeutic level. The time of conception after radioiodine therapy and a high TRAb level are associated with the likelihood of neonatal hyperthyroidism: 8.8% probability if conception occurred 6–12 months after radioiodine therapy, with a 5.5% probability for 12–18 months, and 3.6% probability for 18–24 months. The TRAb value above 10 U/L in the third trimester is the main risk factor for neonatal hyperthyroidism. If a woman does not wish to postpone her family planning, the pre-conceptional counseling has to describe the risk of propylthiouracil, thiamazole, or of an uncontrolled hyperthyroidism. According to some national cohort studies (Danish, Swedish, Korean), the risk for fetal malformations (ear, urinary tract) under propylthiouracil is increased by 1.1–1.6%, in addition to the spontaneous risk for unexposed pregnant women. For thiamazole, the additional risk for fetal malformation was about 2–3%, depending on the dose of thiamazole. Propylthiouracil has posed a lower risk for congenital malformation than an uncontrolled hyperthyroidism. To minimize the risk for the newborn, women with Graves’ disease and hyperthyroidism should offer a definitive therapy strategy (e.g., radioiodine therapy) long before planning a pregnancy. Full article

Graves’ disease (GD) is an autoimmune disorder, driven by the appearance of circulating autoantibodies (Ab) against the thyroid stimulating hormone (TSH) receptor, thus causing hyperthyroidism. While antithyroid drugs, the only available treatment for GD, carry a significant risk of relapse, advances in immunology could pave the way for more effective therapies. Natural killer (NK) cells, divided into cytotoxic CD56^dim and cytokine-secreting CD56^bright subsets, regulate immune responses through cytokine production and cell lysis and may play a role in the pathogenesis of GD. To investigate their involvement, we conducted flow cytometry on peripheral blood samples from 131 GD patients at various stages (disease onset, on antithyroid drugs, and in remission) and 97 age- and sex-matched healthy controls (HC). We analyzed NK cell subsets, activating (CD16, CD69, NKG2D, NKp30) and inhibitory receptors (CD161, NKG2A), degranulation (CD107a), and intracellular cytokines expression (interferon γ, tumor necrosis factor α). Statistical comparisons were made between GD patients and HC and across disease stages. GD patients had a higher frequency of total NK cells (p < 0.028) and CD56^bright NK cells (p < 0.01) but a lower frequency of CD56^dim NK cells (p = 0.005) compared to HC. NK cells in GD patients expressed activating receptors more frequently, except for NKG2D, but had decreased cytokine expression and degranulation ability. At GD onset, patients had higher frequencies of total NK cells, CD56^bright NK cells, and NK cells expressing activating receptors compared to patients receiving ATD treatment and those in remission. CD161⁺ NK cells were lower at GD onset and returned to levels of HC following treatment. Correlation analysis revealed that free thyroxine (FT4) levels were inversely correlated with CD107a⁺ NK cells (p < 0.05) and positively correlated with CD69⁺ NK cells (p < 0.01). These findings suggest that hyperthyroidism impairs NK cell degranulation, with the increased frequency of NK cells potentially compensating for their reduced function. This dysfunction may contribute to the unregulated immune response in GD, highlighting NK cells as a potential target for novel therapeutic strategies. Full article