Prevalence of latent and overt polyautoimmunity in type 1 diabetes: A systematic review and meta-analysis.

BACKGROUND: Patients afflicted by type 1 diabetes (T1D) exhibit polyautoimmunity (PolyA). However, the frequency and distribution of PolyA in T1D is still unknown. OBJECTIVE: We conducted a systematic review and meta-analysis to define the prevalence of latent and overt PolyA in individuals with T1D. METHODS: Following PRISMA guidelines, a comprehensive search across medical databases identified studies on latent and overt PolyA in T1D. Two researchers independently screened, extracted data, and assessed study quality. A random effects model was utilized to calculate the pooled prevalence, along with its corresponding 95 % confidence interval (CI), for latent PolyA and overt PolyA. Meta-regression analysis was conducted to study the effect of study designs, age, sex, and duration of disease on pooled prevalence. RESULTS: A total of 158 articles, encompassing a diverse composition of study designs were scrutinized. The analysis included 270,890 individuals with a confirmed diagnosis of T1D. The gender was evenly distributed (50.30 % male). Notably, our analysis unveiled an overt PolyA prevalence rate of 8.50 % (95 % CI, 6.77 to 10.62), with North America having the highest rates (14.50 %, 95 % CI, 7.58 to 24.89). This PolyA profile was further characterized by a substantial incidence of concurrent autoimmune thyroid disease (7.44 %, 95 % CI, 5.65 to 9.74). Moreover, we identified a notable prevalence of latent PolyA in the T1D population, quantified at 14.45 % (95 % CI, 11.17 to 18.49) being most frequent in Asia (23.29 %, 95 % CI, 16.29 to 32.15) and Oceania (21.53 %, 95 % CI, 16.48 to 27.62). Remarkably, this latent PolyA phenomenon primarily featured an array of autoantibodies, including rheumatoid factor, followed by Ro52, thyroid peroxidase antibodies, and thyroglobulin antibodies. Duration of the disease was associated with a highest frequency of latent (ß: 0.0456, P-value: 0.0140) and overt PolyA (ß: 0.0373, P-value: 0.0152). No difference in the pooled prevalence by study design was observed. CONCLUSION: This meta-analysis constitutes a substantial advancement in the realm of early detection of PolyA in the context of T1D. Individuals with T1D should regularly undergo assessments to identify potential concurrent autoimmune diseases, especially as they age.

Clinical and molecular impact of concurrent thyroid autoimmune disease and thyroid cancer: From the bench to bedside.

The recent incorporation of immune checkpoint inhibitors targeting the PD-1 (programmed cell death receptor 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) pathways into the therapeutic armamentarium of cancer has increased the need to understand the correlation between the immune system, autoimmunity, and malignant neoplasms. Both autoimmune thyroid diseases and thyroid cancer are common clinical conditions. The molecular pathology of autoimmune thyroid diseases is characterized by the important impact of the PD-1/PD-L1 axis, an important inhibitory pathway involved in the regulation of T-cell responses. Insufficient inhibitory pathways may prone the thyroid tissue to a self-destructive immune response that leads to hypothyroidism. On the other hand, the PD-1/PD-L1 axis and other co-inhibitory pathways are the cornerstones of the immune escape mechanisms in thyroid cancer, which is a mechanism through which the immune response fails to recognize and eradicate thyroid tumor cells. This common mechanism raises the idea that thyroid autoimmunity and thyroid cancer may be opposite sides of the same coin, meaning that both conditions share similar molecular signatures. When associated with thyroid autoimmunity, thyroid cancer may have a less aggressive presentation, even though the molecular explanation of this clinical consequence is unclear. More studies are warranted to elucidate the molecular link between thyroid autoimmune disease and thyroid cancer. The prognostic impact that thyroid autoimmune disease, especially chronic lymphocytic thyroiditis, may exert on thyroid cancer raises important insights that can help physicians to better individualize the management of patients with thyroid cancer.

Vitamin B12 levels in thyroid disorders: A systematic review and meta-analysis.

Background and aims: Numerous studies have found an association between vitamin deficiency and thyroid disorders (TD). The presence of anti-parietal cell antibodies is indicative of reduced ability to absorb vitamin B12. Thus, this study reviewed the existing studies with the objective of assessing differences in the serum levels of vitamin B12 among patients with and without TD, the frequency of vitamin B12 deficiency in patients with TD, and the presence of anti-parietal cell antibodies in patients with TD. Methods: A meta-analysis of random-effects model was conducted to calculate pooled frequencies, mean differences (MD), and their respective 95% confidence intervals (CI). We identified 64 studies that met our inclusion criteria (n = 28597). Results: We found that patients with hypothyroidism had lower vitamin B12 levels than healthy participants (MD: -60.67 pg/mL; 95% CI: -107.31 to -14.03 pg/mL; p = 0.01). No significant differences in vitamin B12 levels were observed between healthy participants and patients with hyperthyroidism (p = 0.78), autoimmune thyroid disease (AITD) (p = 0.22), or subclinical hypothyroidism (SH) (p = 0.79). The frequencies of vitamin B12 deficiency among patients with hypothyroidism, hyperthyroidism, SH, and AITD were 27%, 6%, 27%, and 18%, respectively. Conclusions: Patients with hypothyroidism had lower levels of vitamin B12 than healthy participants. No significant differences were observed between vitamin B12 levels and hyperthyroidism, AITD, or SH. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=324422, identifier (CRD42022324422).

[Autoimmunity in chronic urticaria. A historical and current perspective]. / Autoinmunidad en urticaria crónica. Perspectiva histórica y actual.

Chronic spontaneous urticaria is a condition that persists for more than six weeks, it occurs in the absence of an identifiable triggering factor and from the pathogenic activation of mast cells and basophils. The possibility of autoimmune etiology in up to 40 % of patients is presented, followed by subclinical infections and psychological factors. Two main mechanisms of the pathogenesis of chronic urticaria have been proposed: the former is the dysregulation of intracellular signaling pathways within mast cells and basophils, which leads to defects in the traffic or function of these cells. The latter is the development of autoantibodies against FcεRIα or IgE, in both mast cells and basophils. Numerous autoimmune diseases such as systemic lupus erythematosus, polymyositis, dermatomyositis, and rheumatoid arthritis have been associated with chronic urticaria; however, autoimmune thyroid disease deserves a special mention. A higher prevalence of antithyroid antibodies has been found, regardless of thyroid function (euthyroidism, hypo and hyperthyroidism) in patients with chronic spontaneous urticaria. Several infections have been linked to chronic urticaria. The best evidence is for Helicobacter pylori infection. Finally, stress is associated with the onset of the disease through the activation of the sympathetic and adrenomedullary system and the hypothalamic-pituitary- adrenal axis. Diagnosis may vary in different regions of the world, but the common feature is the completion of a thorough medical history.

La urticaria crónica espontánea es una afección que persiste durante más de seis semanas y ocurre en ausencia de un factor desencadenante identificable y resulta de la activación patógena de células cebadas y basófilos. Se plantea la posible etiología autoinmune hasta en 40 % de los pacientes, seguida de infecciones subclínicas y factores psicológicos. Se han propuesto dos mecanismos principales de la patogénesis de la urticaria crónica: la desregulación de las vías de señalización intracelular dentro de las células cebadas y basófilos que conduce a defectos en el tráfico o la función de estas células, así como el desarrollo de autoanticuerpos contra FcεRIα o IgE, tanto en células cebadas como en basófilos. Numerosas enfermedades autoinmunes como lupus eritematoso sistémico, polimiositis, dermatomiositis y artritis reumatoide se han asociado a urticaria crónica; sin embargo, la enfermedad tiroidea autoinmune merece una mención especial. Se ha encontrado una mayor prevalencia de anticuerpos antitiroideos, independientemente de la función tiroidea (eutiroidismo, hipo e hipertiroidismo), en pacientes con urticaria crónica espontánea. Varias infecciones se han relacionado a urticaria crónica. Existe la mejor evidencia de infección por Helicobacter pylori. Por último, el estrés está asociado al inicio de la enfermedad mediante la activación del sistema simpático y adrenomedular y el eje hipotálamo hipófisis suprarrenal. El diagnóstico puede variar en las diferentes regiones del mundo, pero el rasgo común es la realización de una historia clínica completa.

Autoimmune Thyroid Disease in Primary Sjögren's Syndrome: Real-life Screening Practice and Clinical Outcomes.

BACKGROUND: Notwithstanding the frequent coexistence of autoimmune thyroid disease (ATD) and primary Sjögren's Syndrome (SS), it is still unknown how often this association is studied along with its clinical impact. OBJECTIVE: This study aimed to describe real-world screening practices for ATD in patients with SS and evaluate clinical outcomes of patients with both diagnoses using validated activity and chronicity indexes. METHODS: It is a retrospective study of 223 patients with SS attending a tertiary referral center. Patients were under rheumatology surveillance and might have attended other clinics, including internal medicine and/or endocrinology. We registered glandular and extraglandular features, serology and scored the activity (ESSDAI) and the accrual damage (SSDDI) indexes. We also identified any thyroid function tests (TFT) performed, anti-thyroid antibodies, images, and histological thyroid examinations. A single endocrinologist reviewed all data. RESULTS: One hundred forty-nine patients had at least one set of TFT. Younger age was associated with a lack of screening (OR 0.98, 95 % CI 0.95-0.99, p=0.01). Sixty-nine patients had thyroid disease, with the most common diagnosis being ATD (n=24). Patients with ATD had a lower prevalence of Ro/SSA and anti-La/SSB antibodies but similar cumulative SS activity and damage scores. CONCLUSION: At least one-third of our patients were not screened for thyroid disease, with these patients being the youngest. Thyroid disorders were found in about 40 % of patients with SS, with ATD being the most common. Having SS/ATD did not confer more disease activity or damage accrual. These results highlight the importance of making treating physicians aware of screening for thyroid disease in this population.

New insights into the taxonomy of autoimmune diseases based on polyautoimmunity.

OBJECTIVE: The clinical coexistence of two or more autoimmune diseases (ADs) fulfilling classification criteria is termed "overt polyautoimmunity" (PolyA), whereas the presence of autoantibodies unrelated to an index AD, without clinical criteria fulfillment, is known as "latent PolyA". We aimed to explore a new taxonomy of ADs based on PolyA. METHODS: In a cross-sectional study of 292 subjects, we evaluated the presence of PolyA in 146, 45, 29, 17, and 17 patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), autoimmune thyroid disease (AITD) and systemic sclerosis (SSc), respectively, and 38 healthy controls. Clinical assessment, autoantibody profile (by autoantigen array chip), lymphocytes immunophenotype and cytokine profile (by flow cytometry) were evaluated simultaneously. A mixed cluster methodology was used to classify ADs. RESULTS: Latent PolyA was more frequent than overt PolyA, ranging from 69.9% in RA to 100% in SSc. Nevertheless, both latent and overt PolyA clustered together. Over-expressed IgG autoantibodies were found to be hallmarks for the identification of index ADs. The combination of autoantibodies allowed high accuracy in the classification of ADs. Three well-defined clusters based on PolyA were observed with distinctive clinical and immunological phenotypes. CONCLUSIONS: This proof-of-concept study indicates that ADs can be classified according to PolyA. PolyA should be considered in all studies dealing with ADs, including epidemiological, genetic, and clinical trials.

Incidence of TPOAb over a 4-year follow-up period: results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

ABSTRACT Objective: Although some previous data have suggested a high iodine intake in Brazil, the prevalence of antithyroperoxidase antibodies (TPOAb) in the country is compatible with rates from countries with adequate iodine intake. This observation emphasizes the importance of knowing the incidence of TPOAb in Brazil. Materials and methods: This prospective analysis included euthyroid participants with negative TPOAb at baseline and a thyroid function assessment at a 4-year follow-up. TPOAb was measured by electrochemiluminescence and considered positive when titers were ≥34 IU/mL. TSH and free T4 (FT4) levels were determined by a third-generation immunoenzymatic assay. The incidence of TPOAb is expressed in percentage per year or as a cumulative incidence within the 4-year follow-up period. Results: Of 8,922 euthyroid participants (mean age 51.1 years; 50.9% women) with a negative TPOAb test at baseline, 130 presented incident TPOAb at the 4-year follow-up, yielding an annual incidence of TPOAb of 0.38%/year (95% confidence interval [95% CI], 0.37-0.39%/year) and a cumulative incidence over 4 years of 1.46% (95% CI, 1.21-1.71%). In men, the annual incidence was 0.32% (95% CI, 0.31-0.33%), and the cumulative incidence over 4 years was 1.23% (95% CI, 0.90-1.56%). In women, the annual incidence was 0.43%/year (95% CI, 0.42-0.44%/year) and the cumulative incidence over 4 years was 1.67% (95% CI, 1.30-2.04%). The only factor associated with incident TPOAb was the occurrence of thyroid diseases at follow-up. No differences in TPOAb incidence were detected across ELSA-Brasil research centers. Conclusion: Based on the results of this study, the incidence of TPOAb per year and at a 4-year follow-up period are compatible with those of a country with adequate iodine intake.

Incidence of TPOAb over a 4-year follow-up period: results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

OBJECTIVE: Although some previous data have suggested a high iodine intake in Brazil, the prevalence of antithyroperoxidase antibodies (TPOAb) in the country is compatible with rates from countries with adequate iodine intake. This observation emphasizes the importance of knowing the incidence of TPOAb in Brazil. METHODS: This prospective analysis included euthyroid participants with negative TPOAb at baseline and a thyroid function assessment at a 4-year follow-up. TPOAb was measured by electrochemiluminescence and considered positive when titers were ≥34 IU/mL. TSH and free T4 (FT4) levels were determined by a third-generation immunoenzymatic assay. The incidence of TPOAb is expressed in percentage per year or as a cumulative incidence within the 4-year follow-up period. RESULTS: Of 8,922 euthyroid participants (mean age 51.1 years; 50.9% women) with a negative TPOAb test at baseline, 130 presented incident TPOAb at the 4-year follow-up, yielding an annual incidence of TPOAb of 0.38%/year (95% confidence interval [95% CI], 0.37-0.39%/year) and a cumulative incidence over 4 years of 1.46% (95% CI, 1.21-1.71%). In men, the annual incidence was 0.32% (95% CI, 0.31-0.33%), and the cumulative incidence over 4 years was 1.23% (95% CI, 0.90-1.56%). In women, the annual incidence was 0.43%/year (95% CI, 0.42-0.44%/year) and the cumulative incidence over 4 years was 1.67% (95% CI, 1.30-2.04%). The only factor associated with incident TPOAb was the occurrence of thyroid diseases at follow-up. No differences in TPOAb incidence were detected across ELSA-Brasil research centers. CONCLUSION: Based on the results of this study, the incidence of TPOAb per year and at a 4-year follow-up period are compatible with those of a country with adequate iodine intake.

Disfunción tiroidea y diabetes mellitus tipo 1 / Thyroid dysfunction and type 1 diabetes mellitus

Introducción: La diabetes mellitus tipo 1 es una enfermedad autoinmunitaria que se relaciona con alteraciones tiroideas. Objetivo: Describir la relación que existe entre diabetes mellitus tipo 1 y enfermedad tiroidea autoinmune. Métodos: Se realizó una revisión de la literatura nacional e internacional de los últimos 15 años en bases de datos, en español y en inglés. Se utilizaron las siguientes palabras clave: diabetes mellitus tipo 1, autoinmunidad, enfermad tiroidea autoinmune, disfunción tiroidea y anticuerpos antitiroideos. Análisis e integración de la información: La alteración más frecuente es el hipotiroidismo subclínico y se presenta con mayor frecuencia en el sexo femenino, por lo que se sugiere realizar periódicamente el perfil tiroideo a estos pacientes. Conclusiones: Se debe tener en cuenta en la práctica clínica estas implicaciones para brindar un tratamiento oportuno, mejorar complicaciones derivadas como las enfermedades cardiovasculares y disminuir las cifras de morbilidad y mortalidad(AU)

Introduction: Type 1 diabetes mellitus is an autoimmune disease that is related to thyroid abnormalities. Objective: Describe the relationship between type 1 diabetes mellitus and autoimmune thyroid disease. Methods: A review of the national and international literature of the last 15 years was carried out in databases, in Spanish and in English. The following keywords were used: type 1 diabetes mellitus, autoimmune, autoimmune thyroid disease, thyroid dysfunction and antithyroid antibodies. Analysis and integration of information: The most common alteration is subclinical hypothyroidism and it occurs most often in the female sex, so it is suggested to periodically perform the thyroid profile to these patients. Conclusions: These implications should be taken into account in clinical practice to provide timely treatment, improve complications such as cardiovascular disease and reduce morbidity and mortality figures(AU)

Interplay Between Thyroid Hormone Status and Pulmonary Hypertension in Graves' Disease: Relevance of the Assessment in Thyrotoxic and Euthyroid Patients.

Background: Graves' disease (GD) is the most common cause of hyperthyroidism and can cause cardiac changes, such as pulmonary hypertension. Methods: This is a prospective study in which we obtained demographic, clinical, laboratory data and characteristics of the GD, in addition to investigating cardiorespiratory function, focusing on the detection of pulmonary hypertension. Patients were separated into two groups: thyrotoxicosis and euthyroidism. Ninety patients with GD of both sexes, over 18 years of age, were included. The cardiorespiratory assessment included an echocardiographic evaluation, a questionnaire of specific symptoms, spirometry and a six-minute walk test. Results: The hyperthyroid group included 42 patients (47.73%) and the euthyroid group 46 patients (52.27%); 78 were women (86.67%). The prevalence of pulmonary hypertension between the hyperthyroidism (48.57%) and the euthyroidism (29.41%) groups was not different. Free thyroxine levels (FT4) (OR 1.266), higher left atrium volume (OR 1.113) and right ventricle diameter were associated with pulmonary hypertension. A direct correlation between FT4 with forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1), as also an inverse correlation between initial oxygen saturation (SpO2) with diagnostic time and drop SpO2 with the ratio between the diastolic velocity E of the mitral flow and the diastolic velocity of the mitral ring (E/e') were observed in the euthyroid group. An inverse correlation between FT4 levels with walked distance as % of predicted value, and a direct correlation between E/e' ratio and walked distance as % of predicted value were observed in the hyperthyroid group. Conclusion: We emphasize the importance of a cardiorespiratory reassessment in GD, even after a long-term control of the thyrotoxic state, as we demonstrate that about 30% of these patients remain with PH and are subject to specific treatment.

Autoinmunidad tiroidea en mujeres con Síndrome de Ovario Poliquístico / Thyroid autoimmunity in women with polycystic ovary syndrome

Introducción: Las bases fisiopatológicas del Síndrome de ovario poliquístico pueden predisponer a mayor riesgo de autoinmunidad a las mujeres que tienen esta condición y existen evidencias, aunque escasas, de mayor prevalencia de autoinmunidad tiroidea en ellas. Objetivos: Determinar la frecuencia de marcadores serológicos de autoinmunidad tiroidea en mujeres con Síndrome de ovario poliquístico e identificar si existe asociación entre la presencia de ellos y las concentraciones de progesterona y testosterona. Métodos: Se realizó un estudio en 50 mujeres con Síndrome de ovario poliquístico y 50 sin el síndrome. Se realizaron determinaciones de autoanticuerpos tiroideos (anti tiroglobulina (Anti-Tg) y anti peroxidasa (anti-TPO) a las mujeres de ambos grupos de estudio. Se realizaron determinaciones de hormonas (testosterona y progesterona) solo al grupo de estudio de mujeres con SOP. Se crearon categorías por anticuerpos: Positivo si los títulos fueron superior al rango de referencia y negativo dentro del rango. Se consideró respuesta autoinmune positiva, cuando al menos uno de los anticuerpos se encontró elevado. Para la asociación entre la presencia de autoinmunidad y las variables independientes se hicieron análisis bivariados mediante comparación de medias y test no paramétricos. Se consideró un nivel de significancia de α = 0,05. Resultados: En las mujeres con Síndrome de ovario poliquístico, 62 por ciento mostraron anticuerpos positivos y 14 por ciento en las sin el síndrome. En las mujeres sin síndrome, de las 7 mujeres con marcadores de autoinmunidad positivos, en 6 (85,7 por ciento) el anti-Tg fue el que dio positivo. No hubo diferencias significativas en cuanto a la asociación con los niveles de testosterona y progesterona. Conclusiones: Las mujeres con Síndrome de ovario poliquístico tienen mayor frecuencia de desarrollar respuesta autoinmune tiroidea, independiente de los niveles de progesterona y testosterona(AU)

Introduction: The physio-pathological bases of polycystic ovary syndrome may predispose women with this condition to a higher risk of autoimmunity and there is evidence, albeit scarce, of higher prevalence of thyroid autoimmunity in them. Objectives: Determine the frequency of serological markers of thyroid autoimmunity in women with polycystic ovary syndrome and identify whether there is an association between the presence of them and progesterone and testosterone concentrations. Methods: A study was conducted in 50 women with polycystic ovary syndrome and 50 without the syndrome. Determinations of thyroid autoantiantibodies (anti-thyroglobulin (Anti-Tg) and anti-peroxidase (anti-TPO) were made to women in both study groups. Hormone determinations (testosterone and progesterone) were made only to the study group of women with PCOS. Categories were created by antibodies: Positive if the titles were greater than the reference range, and negative if within the range. It was considered a positive autoimmune response when at least one of the antibodies was found increased. For the association between the presence of autoimmunity and independent variables, bivariate analyses were performed by means comparison and non-parametric tests. It was considered a significance level of α =0.05. Results: In women with polycystic ovary syndrome, 62 percent showed positive antibodies and 14 percent in those without the syndrome. In women without the syndrome, of the 7 women with positive autoimmune markers, in 6 (85.7 percent) the anti-Tg was the one that tested positive. There were no significant differences in the association with testosterone and progesterone levels. Conclusions: Women with polycystic ovary syndrome are more often able to develop thyroid autoimmune response, independently from the progesterone and testosterone levels(AU)

Latent autoimmune thyroid disease.

OBJECTIVE: To determine the prevalence of thyroid autoantibodies and the associated factors in euthyroid subjects. METHODS: 300 euthyroid subjects, chosen by stratified sampling from an inception cohort of 1335 individuals, were included. Thyroid function was evaluated by measuring the serum levels of TSH (0.3-4.5 µIU/mL) and FT4 (5.2-12.7µg/dL). Anti-peroxidase (TPOAbs), anti-thyroglobulin (TgAbs), and anti-TSH receptor (TrAbs) antibodies were evaluated with 23 additional autoantibodies as well as vitamin D (VitD) levels. The analysis included sociodemographic, clinical, and environmental characteristics. Data were analyzed by bivariate and multivariate tests. RESULTS: Thyroid autoimmunity was observed in 15.3% of the subjects (TPOAbs 11.3% and TgAbs 2.0%). In six individuals, both autoantibodies were positive. TrAbs were not detected in any individual. Familial thyroid disease (ߠ​= â€‹3.4, 95% CI: 1.2-9.5, P â€‹= â€‹0.021), the presence of other autoimmune diseases (ߠ​= â€‹10.8, 95% CI: 1.6-72.9, P â€‹= â€‹0.014) VitD insufficiency (P â€‹= â€‹0.030), never smoke (ߠ​= â€‹6.9, 95% CI: 1.6-30.4, P â€‹= â€‹0.010), drinking more than 4 cups of coffee (ߠ​= â€‹3.8, 95% CI: 1.1-13.1, P â€‹= â€‹0.036), and a higher number of years exposed to wood smoke (P â€‹= â€‹0.04) were associated with thyroid autoimmunity. In the case of TPOAbs, familial thyroid disease (ߠ​= â€‹4.9, 95% CI: 1.7-14.0, P â€‹= â€‹0.003), never smoke (ߠ​= â€‹5.7, 95% CI: 1.4-21.0, P â€‹= â€‹0.002), and drinking more than 4 cups of coffee (ߠ​= â€‹3.6, 95% CI: 1.1-13.1, P â€‹= â€‹0.047) were associated with their positivity. In addition, the presence of anti-SS-A/Ro52 (ߠ​= â€‹36.7, 95% CI: 2.5-549.9, P â€‹= â€‹0.009) and anti-Ku antibodies (ߠ​= â€‹10.2, 95% CI: 1.1-100.7, P â€‹= â€‹0.046) was also associated with TPOAbs. The presence of African ancestry (ߠ​= â€‹10.5, 95% CI: 1.7-63.2, P â€‹= â€‹0.01), anti-SS-A/Ro52 (ߠ​= â€‹15.8, 95% CI: 1.2-198.6, P â€‹= â€‹0.03), and anti-CENP-B antibodies (ߠ​= â€‹31.2, 95% CI: 1.8-565.9 â€‹P â€‹= â€‹0.02) were associated with TgAbs. CONCLUSION: Latent thyroid autoimmunity is not rare. Environmental, genetic, and immunological factors as well as ancestry are associated risk factors. These results would facilitate the implementation of screening strategies in order to provide timely diagnosis and treatment.

Aspartic acid70 in the HLA-DRB1 chain and shared epitope alleles partially explain the high prevalence of autoimmunity in Mexicans.

INTRODUCTION: Autoimmune thyroid disease (AITD) is the most common autoimmune disorder worldwide. Remarkably, it is commonly accompanied by other autoimmune diseases, such as rheumatoid arthritis (RA). The immunopathogenic mechanisms behind the coexistence of these disorders are still not completely understood. Immunogenetics influences the physiopathology of these diseases since ethnicity plays an essential role in the inheritance of susceptibility markers. METHODS: High-resolution HLA class II typing was performed using a sequence-based method. RESULTS: The allele frequency of HLA-DRB1∗04:04 and -DRB1∗03:01 were significantly increased in patients with AITD and RA compared to healthy individuals, pC â€‹= â€‹0.021, OR â€‹= â€‹2.4, 95%CI â€‹= â€‹1.19-4.75 and pC â€‹= â€‹0.009, OR â€‹= â€‹3.4, 95%CI â€‹= â€‹1.42-7.93, respectively. Remarkably, these patients have a combined risk given by susceptibility HLA-DRB1 alleles that contain the shared epitope, pC â€‹= â€‹0.03, OR â€‹= â€‹1.7, IC95% â€‹= â€‹1.07-2.76, and a lack of protective alleles carrying aspartic acid70, pC â€‹= â€‹0.009, OR â€‹= â€‹0.5, IC95% â€‹= â€‹0.32-0.84. DISCUSSION: The results suggest that patients with AITD and RA have an immunogenetic mechanism that combines the susceptibility alleles associated with both diseases. Importantly, it seems to be linked mainly to the lack of protective alleles with aspartic acid in the position 70, along with the presence of susceptibility alleles that have the sequences QRRAA, QKRAA, and RRRAA at positions 70-74. CONCLUSION: Patients with AITD and RA have a characteristic immunogenetic signature, which could be useful for determining multiple autoimmunities and assessing their relatives' risk of developing it.

Prevalence of latent and overt polyautoimmunity in autoimmune thyroid disease: A systematic review and meta-analysis.

BACKGROUND: Thyroid autoimmunity is the most frequent condition involved in polyautoimmunity (PolyA). However, the frequency of latent and overt PolyA in patients with autoimmune thyroid disease (AITD) as the index condition is unknown. Therefore, the purpose of this study was to determine the prevalence of these types of PolyA in patients with AITD as the index condition. METHODS: This study adhered to the relevant sections of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. Searches through MEDLINE, Embase and LILACS were done to find articles in Spanish and English. Relevant vocabulary terms and key terms related to AITD and other autoimmune diseases were used. Two investigators independently screened the eligible studies, extracted data and assessed the quality and risk of bias. Fixed and random effect models were used accordingly. Cluster analysis was used to determine similarities among diseases in the articles included (based on Jaccard index). RESULTS: A total of 56 articles fulfilled the inclusion criteria. Of these, 25 were case-controls, 17 were cohorts, and 14 were cross-sectional studies. These studies included a total of 47 509 patients. Female was the predominant gender and included 38 950 patients (81.23%, 95% CI: 80.85-81.60). Graves' disease (GD) was the most common type of thyroid autoimmunity (69.16%, 95% CI: 68.23-70.07). Globally, overt PolyA was found in 13.46% of the patients with AITD. This type of PolyA was represented mainly by type 1 diabetes and autoimmune gastritis. Latent PolyA was presented in 17.45% of the patients, and anti-proinsulin, anti-parietal cells and dsDNA antibodies were the most common. HT had the highest frequency of overt PolyA in Europe (15.60%, 95% CI: 14.72-16.53), whereas latent PolyA was most common in patients with GD in Asia (21.03%, 95% CI: 17.76-24.71). Overt and latent PolyA were associated with gastrointestinal and endocrinological ADs in most of cases and clustered with rheumatological, dermatological and neurological ADs. CONCLUSIONS: Latent and overt PolyA are common in patients with AITD. These results provide insightful information for early diagnosis and management of concurrent ADs in patients with AITD. Aggregation of ADs in different clusters may help to define different phenotypes associated with thyroid autoimmunity that are critically relevant in clinical settings.

Chronic urticaria and thyroid pathology.

Urticaria is defined as the sudden appearance of erythematous, itchy wheals of variable size, with or without angioedema (AE) (swelling of the deeper layers of the skin). Its classification depends on time course of symptoms and the presence of eliciting factors. When it lasts less than 6 weeks it is classified as acute urticaria (AU), and if the symptoms persist for more than 6 weeks, it is classified as chronic urticaria (CU). Current International Guidelines also classify CU as chronic spontaneous urticaria (CSU) and inducible urticarial, according to the absence or presence of environmental triggering factors. CSU is defined as urticaria and/or angioedema in which there is no evidence of a specific eliciting factor. CSU is associated with autoimmunity in 30-45% of the cases, sharing some immunological mechanisms with other autoimmune diseases, and is associated with autoimmune thyroid disease (ATD) in about 4.3%-57.4% patients. Several studies suggest that adequate therapy with anti-thyroid drugs or levothyroxine in early stages of ATD and CSU, may help to remit the latter; but there is still a lack of double-blind, placebo-controlled studies that support this hypothesis in patients without abnormal thyroid hormone levels. The objective of this review is to describe the pathophysiology of chronic spontaneous urticaria and its association with autoimmune thyroid disease.

Cytotoxic T Lymphocyte-associated Antigen 4 Polymorphisms Correlated with Graves' Disease in Patients of Han Ethnicity in Yunnan, China / Polimorfismos del antígeno 4 del linfocito T citotóxico correlacionados con la enfermedad de Graves en pacientes de la etnia Han en Yunnan, China

ABSTRACT Objective: To investigate the correlations between polymorphisms at position 49 in exon 1 and position 318 in the promoter of the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene and autoimmune thyroid diseases in a Han Chinese population. Methods: Polymerase chain reaction-restriction fragment length polymorphism was utilized. The MseI and BbvI restriction endonucleases were used to detect and analyse position 49 in exon 1 and position 318 in the promoter as well as the T/C alleles of the CTLA-4 gene in peripheral blood samples from 112 patients with Graves' disease (GD), 101 with Hashimoto's thyroiditis (HT) and 100 healthy individuals. Results: At position 49 of exon 1, the frequencies of the GG genotype and the G allele in the GD group (χ2 = 12.147; p = 0.002) were statistically significantly higher than those in the control group (χ2 = 9.925; p = 0.002), while no statistically significant differences were found between the frequencies of the GG genotype and the G allele in the HT group (χ2 = 1.195; p = 0.550) and those in the control group (χ2 = 0.984; p = 0.321). No statistically significant differences in the promoter (−318) or the T/C alleles were observed among the three groups. Position 49 in the 17th codon of exon 1 of the CTLA-4 gene may be a candidate susceptibility marker in patients of Han ethnicity with GD. Conclusion: This finding helps us to better understand the genetic risks for GD and provides a direction for targeted gene therapy.

RESUMEN Objetivo: Investigar las correlaciones entre los polimorfismos en la posición 49 en el exón 1 y la posición 318 en el promotor del gen del antígeno 4 asociado al linfocito T citotóxico (CTLA-4), con las enfermedades autoinmunes de la tiroides en una población China de Han. Métodos: Se utilizó la reacción en cadena de la polimerasa-polimorfismo de la longitud de los fragmentos de restricción. Las endonucleasas de restricción de MseI y BbvI se utilizaron para detectar y analizar la posición 49 en el exón 1 y la posición 318 en el promotor, así como los alelos T/C del gen CTLA-4 en muestras de sangre periférica de 112 pacientes con enfermedad de Graves (EG), 101 con tiroiditis de Hashimoto (TH) y 100 individuos sanos. Resultados: En la posición 49 de exón 1, las frecuencias del genotipo GG y el alelo G en el grupo de EG (χ2 = 12.147; p = 0.002) fueron estadísticamente significativamente más altas que las del grupo de control (χ2 = 9.925; p = 0.002), pero no se encontraron diferencias estadísticamente significativas entre las frecuencias del genotipo GG y el alelo G en el grupo de TH (χ2 = 1.195; p = 0.550) y las del grupo de control (χ2 = 0.984; p = 0.321). No se observaron diferencias estadísticamente significativas en el promotor (−318) ni en los alelos T/C entre los tres grupos. La posición 49 en el codón17.° del exón 1 del gen CTLA-4 puede ser un marcador de susceptibilidad candidato en pacientes de la etnia Han con EG. Conclusión: Este hallazgo nos ayuda a comprender mejor los riesgos genéticos de la EG y ofrece una dirección para la terapia génica dirigida.

Polyglandular syndrome type 2 in a Mexican family and its association with human leukocyte antigen.

The evaluation of first-degree family members is very important to detect additional cases of polyglandular autoimmune syndrome type 2. The genetic evaluation of human leukocyte antigen (HLA) may be useful in the study of this syndrome. This study is the first report of an HLA study of this syndrome in a Mexican family.

Sjögren's Syndrome and Autoimmune Thyroid Disease: Two Sides of the Same Coin.

The coexistence of Sjögren's syndrome (SS) and autoimmune thyroid disease (AITD) has been documented. However, there is no consensus whether this coexistence should be considered as the same nosological condition or as polyautoimmunity. Thus, in this monocentric retrospective study, patients with SS alone (i.e., primary) were compared with patients with SS and AITD. In addition, a discussion of previous studies including those about genetic and environmental factors influencing the development of both conditions is presented. In our series, all patients with AITD had Hashimoto's thyroiditis (HT). No significant differences in age, gender, age of disease onset, and disease duration were found between the two groups. Lymphadenopathy and urticaria were more frequently registered in patients with SS-HT than in patients with SS alone (p < 0.05). Anti-Ro/SSA antibodies were more frequent in the primary SS group (p = 0.01). SS-HT patients were more likely to report a positive history of smoking (p = 0.03). The clinical expression of SS varies slightly when HT coexists. Although both entities share common physiopathological mechanisms as part of the autoimmune tautology, they are nosologically different and their coexistence should be interpreted as polyautoimmunity. Further studies based on polyautoimmunity would allow establishing a new taxonomy of autoimmune diseases.

Commentary: Health Concerns of Brazil Nut Consumption.

Brazil nuts are the fruit of the enormous tropical tree Bertholletia excelsa that are produced in and exported from the territory of the Amazon. As a natural rich source of selenium (Se), the consumption of Brazil nuts is often suggested as therapeutic among patients with autoimmune thyroid diseases. In this review, the current knowledge regarding the main health concerns of Brazil nut consumption, such as Se toxicity, Se-induced type 2 diabetes mellitus, weight gain, radioactivity, aflatoxins, and allergic reactions, is presented and discussed.

Prevalence of pancreatic autoantibodies in non-diabetic patients with autoimmune thyroid disease and its relation to insulin secretion and glucose tolerance

ABSTRACT Objective We evaluated the prevalence of glutamic acid decarboxylase (GADA) and tyrosine phosphatase-protein antibodies (IA2A), their titers and their relation to first phase insulin response (FPIR) and glucose tolerance in autoimmune thyroid diseases (ATDs) patients. Subjects and methods Graves' disease (GD; n = 181) and Hashimoto's thyroiditis (HT; n = 143) patients in addition to healthy controls (n = 93) were studied. Secondly, FPIR and oral glucose tolerance tests (OGTT) were performed in 11 anti-pancreatic islet-cell (+) and in 20 anti-pancreatic-cell (-) patients. Results There was a non significant trend for higher prevalence of GADA positivity in GD vs HT (7.2% vs 2% p = 0.06), but the GADA titers were higher in HT. We also did not find a significant difference in IA2 prevalence (0.7% vs 0.0%) between these two groups or compared to the control group. In the subsequent analysis, low FPIR was found in 10% of these patients but without statistical difference for OGTT between pancreatic antibody-positive and -negative patients. Conclusion A trend for greater prevalence of GADA was observed for GD patients than for HT or control. However, the titers of these autoantibodies were higher in HT patients, but there was no significant relation to insulin secretion and glucose tolerance at that moment and stage of autoimmune diseases.