RESUMEN
The novel coronavirus disease COVID-19 is produced by SARS-CoV-2. WHO has declared COVID-19 as a public health emergency, with the most susceptible populations (requiring ventilation) being the elderly, pregnant women and people with associated co-morbidities including heart failure, uncontrolled diabetes, chronic obstructive pulmonary disease, asthma and cancer. However, such general guidance does not provide information regarding COVID-19 risks in patients with suffering from pre-existing thyroid problems, and furthermore, we do not know whether patients with COVID-19 (symptomatic or without symptoms), who have not previously had thyroid issues develop endocrine thyroid dysfunction after infection. The European Society for Endocrinology recently published a statement on COVID-19 and endocrine diseases (Endocrine, 2020); however, thyroid diseases were not mentioned specifically. We have therefore reviewed the current literature on thyroid diseases (excluding cancer) and COVID-19, including data from the previous coronavirus pandemic caused by the SARS-associated coronavirus (SARS-CoV), a member of the same family Coronaviridae leading to severe acute respiratory syndrome (SARS). At the moment there are no data suggesting that thyroid patients are at higher risk of COVID-19, but this requites further research and data analysis.
Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/complicaciones , Neumonía Viral/complicaciones , Enfermedades de la Tiroides/complicaciones , COVID-19 , Infecciones por Coronavirus/inmunología , Humanos , Pandemias , Neumonía Viral/inmunología , Factores de Riesgo , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , SARS-CoV-2 , Síndrome Respiratorio Agudo Grave , Enfermedades de la Tiroides/inmunología , Enfermedades de la Tiroides/virología , Tiroiditis Autoinmune/virologíaRESUMEN
ABSTRACT Background - Exposure to viral antigens that share amino acid sequence similar with self- antigens might trigger autoimmune diseases in genetically predisposed individuals, and the molecular mimicry theory suggests that epitope mimicry between the virus and human proteins can activate autoimmune disease. Objective - The purpose of this study is to explore the possible sequence similarity between the amino acid sequences of thyroid self-protein and hepatitis C virus proteins, using databanks of proteins and immunogenic peptides, to explain autoimmune thyroid disease. Methods - Were performed the comparisons between the amino acid sequence of the hepatitis C virus polyprotein and thyroid self-protein human, available in the database of National Center for Biotechnology Information on Basic Local Alignment Search Tool. Results - The sequence similarity was related each hepatitis C virus genotype to each thyroid antigen. The similarities between the thyroid and the viral peptides ranged from 21.0 % (31 identical residues out of 147 amino acid in the sequence) to 71.0% (5 identical residues out of 7 amino acid in the sequence). Conclusion - Bioinformatics data, suggest a possible pathogenic link between hepatitis C virus and autoimmune thyroid disease. Through of molecular mimicry is observed that sequences similarities between viral polyproteins and self-proteins thyroid could be a mechanism of induction of crossover immune response to self-antigens, with a breakdown of self-tolerance, resulting in autoimmune thyroid disease.
RESUMO Contexto - A exposição a antígenos virais que compartilham sequência de aminoácidos semelhantes a auto-antígenos pode provocar doenças auto-imunes em indivíduos predispostos geneticamente, e a teoria do mimetismo molecular sugere que o mimetismo entre epítopos de vírus e proteínas humanas pode ativar doenças auto-imunes. Objetivo - O objetivo deste estudo foi explorar a possível semelhança entre as sequências de aminoácidos de auto-proteinas da tireóide e proteínas do vírus da hepatite C, utilizando bancos de dados de proteínas e peptídeos imunogênicos, para explicar a doença auto-imune da tireóide. Métodos - Foram realizadas comparações entre as sequências de aminoácidos de poliproteínas do vírus da hepatite C e auto-proteinas da tireóide humana, disponível na base de dados do National Center for Biotechnology Information no Basic Local Alignment Search Tool. Resultados - A semelhança de sequências foi relacionada para cada genótipo de vírus da hepatite C e proteínas da tireóide. As semelhanças entre proteínas da tireóide e os peptídeos virais variaram de 21,0% (31 resíduos idênticos da sequência de 147 aminoácidos) a 71,0% (cinco resíduos idênticos da sequência de 7 aminoácidos). Conclusão - Dados de bioinformática sugerem uma possível ligação entre vírus da hepatite C e doença auto-imune da tireóide. Através de mimetismo molecular observa-se que as semelhanças entre as sequências de poliproteínas virais e auto-proteínas da tireóide pode ser um mecanismo de indução de resposta imune resultando em doença auto-imune da tireóide.
Asunto(s)
Humanos , Autoantígenos/genética , Proteínas Virales/genética , Tiroiditis Autoinmune/inmunología , Homología de Secuencia de Aminoácido , Hepacivirus/genética , Poliproteínas/genética , Tiroiditis Autoinmune/virología , Hepacivirus/inmunología , Imitación Molecular/genética , Técnicas de Genotipaje , Epítopos/genéticaRESUMEN
BACKGROUND: - Exposure to viral antigens that share amino acid sequence similar with self- antigens might trigger autoimmune diseases in genetically predisposed individuals, and the molecular mimicry theory suggests that epitope mimicry between the virus and human proteins can activate autoimmune disease. OBJECTIVE: - The purpose of this study is to explore the possible sequence similarity between the amino acid sequences of thyroid self-protein and hepatitis C virus proteins, using databanks of proteins and immunogenic peptides, to explain autoimmune thyroid disease. METHODS: - Were performed the comparisons between the amino acid sequence of the hepatitis C virus polyprotein and thyroid self-protein human, available in the database of National Center for Biotechnology Information on Basic Local Alignment Search Tool. RESULTS: - The sequence similarity was related each hepatitis C virus genotype to each thyroid antigen. The similarities between the thyroid and the viral peptides ranged from 21.0 % (31 identical residues out of 147 amino acid in the sequence) to 71.0% (5 identical residues out of 7 amino acid in the sequence). CONCLUSION: - Bioinformatics data, suggest a possible pathogenic link between hepatitis C virus and autoimmune thyroid disease. Through of molecular mimicry is observed that sequences similarities between viral polyproteins and self-proteins thyroid could be a mechanism of induction of crossover immune response to self-antigens, with a breakdown of self-tolerance, resulting in autoimmune thyroid disease.
Asunto(s)
Autoantígenos/genética , Hepacivirus/genética , Poliproteínas/genética , Homología de Secuencia de Aminoácido , Tiroiditis Autoinmune/inmunología , Proteínas Virales/genética , Epítopos/genética , Técnicas de Genotipaje , Hepacivirus/inmunología , Humanos , Imitación Molecular/genética , Tiroiditis Autoinmune/virologíaRESUMEN
Interferon (IFN)-γ-induced protein 10 (IP-10/CXCL10) and its receptor, C-X-C motif receptor 3, appear to contribute to the pathogenesis of hepatitis C virus (HCV)-related mixed cryoglobulinaemia (MC) (HCV+MC). The secretion of CXCL10 by cluster of differentiation (CD) CD4+, CD8+, and natural killer-T cells is dependent on IFN-γ, which is itself mediated by the interleukin-12 cytokine family. Under the influence of IFN-γ, CXCL10 is secreted by several cell types including lymphocytes, hepatocytes, endothelial cells, fibroblasts, etc. In tissues, recruited T helper 1 lymphocytes may be responsible for enhanced IFN-γ and tumour necrosis factor-α production, which in turn stimulates CXCL10 secretion from the cells, therefore creating an amplification feedback loop, and perpetuating the autoimmune process. High levels of CXCL10 in circulation have been found in HCV+MC, especially in patients with clinically active vasculitis. Furthermore, HCV+MC patients with autoimmune thyroiditis (AT) have higher levels than those without AT. Further studies are needed to investigate interactions between chemokines and cytokines in the pathogenesis, and to evaluate whether CXCL10 is a novel therapeutic target in HCV-related MC.
Asunto(s)
Quimiocina CXCL10/metabolismo , Crioglobulinemia/metabolismo , Linfocitos T/metabolismo , Animales , Quimiocina CXCL10/inmunología , Crioglobulinemia/inmunología , Crioglobulinemia/virología , Hepacivirus/inmunología , Hepatitis C/complicaciones , Hepatitis C/inmunología , Interacciones Huésped-Patógeno , Humanos , Interferón gamma/metabolismo , Transducción de Señal , Linfocitos T/inmunología , Linfocitos T/virología , Tiroiditis Autoinmune/inmunología , Tiroiditis Autoinmune/virología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
A middle aged woman, previously healthy with the exception of mild seasonal asthma was presented with signs of acute hepatitis. The further investigation showed acute hepatitis E virus infection associated with autoimmune thyroiditis. Treatment was started with propranolol and carbimazol whereupon hepatitis and hyperthyroidism resolved. The authors think that the observed association of acute hepatitis E virus infection and autoimmune thyroiditis suggests a role of hepatitis E virus as putative trigger of autoimmune thyroiditis. The alternative possibility of thyroid dysfunction due to pre-existing autoantibodies cannot be completely excluded but seems to be unlikely given the very mild course of seasonal asthma in this patient.
Asunto(s)
Hepatitis E/complicaciones , Tiroiditis Autoinmune/virología , Antagonistas Adrenérgicos beta/uso terapéutico , Antitiroideos/uso terapéutico , Carbimazol/uso terapéutico , Diagnóstico Diferencial , Quimioterapia Combinada , Femenino , Hepatitis E/diagnóstico , Hepatitis E/tratamiento farmacológico , Hepatitis E/inmunología , Humanos , Pruebas de Función Hepática , Persona de Mediana Edad , Propranolol/uso terapéutico , Tiroiditis Autoinmune/diagnóstico , Tiroiditis Autoinmune/tratamiento farmacológico , Tiroiditis Autoinmune/inmunologíaRESUMEN
INTRODUCTION: Autoimmune diseases are complex diseases with genetic, endogenous and environmental etiologies. Viral infections have been postulated as one of the factors that may be the trigger of autoimmune diseases. METHODOLOGY: Thyroid peroxidase (TPO) and thyroglobulin (TG) antibodies were measured before thyroidectomy in 100 subjects by chemiluminescence method, 50 of whom were autoimmune thyroid diseases (AITD) patients and 50 of whom were multinodular goiter (MNG) patients used as a control group. Fresh thyroid samples were collected from all 100 subjects after thyroidectomy to investigate the DNAs of herpes simplex viruses types 1 and 2 (HSV-1, HSV-2), Varicella Zoster virus (VZV), Epstein-Barr virus (EBV), Cytomegalovirus (CMV) and human herpes virus type 6 (HHV-6) by PCR. RESULTS: The DNA of HSV-1, HSV-2, VZV, EBV, CMV and HHV-6 were detected in neither the patient group nor in the control group. The mean values of anti-TPO and anti-TG antibodies ranged within 9.5-2000 units/ml (527.8 ± 617.4) and 108-5000 units/ml (1458.2 ± 1774.1) in the AITD patients group, respectively. A statistically significant difference of the mean level of anti-TPO and anti-TG antibodies among the two groups was found (p value < 0.05). CONCLUSIONS: The possible role of human herpes viruses in the pathogenesis of AITD is not supported by our study; hence our raised question stays open for more investigation on more patients and in different parts of the country using different sizes and sites of biopsies.
Asunto(s)
Autoanticuerpos/sangre , ADN Viral/aislamiento & purificación , Infecciones por Herpesviridae/complicaciones , Herpesviridae/aislamiento & purificación , Glándula Tiroides/virología , Tiroiditis Autoinmune/patología , Tiroiditis Autoinmune/virología , Adulto , ADN Viral/genética , Humanos , Yoduro Peroxidasa/inmunología , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Tiroglobulina/inmunología , TiroidectomíaRESUMEN
HCV infection is well-known to be associated with autoimmune thyroiditis. However, the mechanisms by which HCV triggers thyroiditis are unknown. We hypothesized that HCV envelope proteins could induce thyroidal inflammation directly, thereby triggering thyroiditis by a bystander activation mechanism. To test this hypothesis we examined whether the HCV receptor CD81 was expressed and functional on thyroid cells. We found significant levels of CD81 mRNA by QPCR analysis, as well as CD81 protein by flow cytometric (FACS) analysis. Incubation of thyroid cells with HCV envelope glycoprotein E2 resulted in E2 binding to thyroid cells and activation of IL-8, an important pro-inflammatory cytokine. Intriguingly, thyroid cells incubated with E2 continued to proliferate normally and did not undergo apoptosis, as was reported in hepatocytes. We conclude that: (1) HCV envelope glycoprotein E2 can bind to CD81 receptors which are expressed on thyroid cells and induce a cascade of signaling pathway leading to IL-8 release; and (2) HCV may trigger thyroiditis in genetically susceptible individuals by bystander activation mechanisms.
Asunto(s)
Hepacivirus/inmunología , Interleucina-8/inmunología , Glándula Tiroides/virología , Tiroiditis Autoinmune/virología , Proteínas del Envoltorio Viral/inmunología , Antígenos CD/inmunología , Autoinmunidad , Células Cultivadas , Humanos , Interleucina-8/biosíntesis , Tetraspanina 28 , Glándula Tiroides/inmunología , Glándula Tiroides/metabolismo , Tiroiditis Autoinmune/inmunologíaRESUMEN
Different types of infection are implicated in the pathogenesis of autoimmune thyroid diseases (AITD) through molecular mimicry or other mechanisms, but their role is disputed. Human studies support direct or indirect evidence of involvement of some viral and bacterial agents, but reports have provided conflicting and inconclusive results. Using a new automated multiplex array platform for the detection of antibodies, we determined seroreactivity against Toxoplasma gondii, Treponema pallidum, rubella virus, cytomegalovirus, and Epstein-Barr virus in a large group of Italian AITD patients and healthy controls. Only IgG concentrations against T. gondii were significantly higher in AITD patients than in controls, suggesting that these protozoa may be involved in the initiation of both Hashimoto's thyroiditis and Graves' disease.
Asunto(s)
Anticuerpos/análisis , Infecciones/inmunología , Análisis por Matrices de Proteínas , Tiroiditis Autoinmune/inmunología , Animales , Citomegalovirus/inmunología , Herpesvirus Humano 4/inmunología , Humanos , Infecciones/microbiología , Infecciones/parasitología , Infecciones/virología , Proteómica , Virus de la Rubéola/inmunología , Tiroiditis Autoinmune/microbiología , Tiroiditis Autoinmune/parasitología , Tiroiditis Autoinmune/virología , Toxoplasma/inmunología , Treponema pallidum/inmunologíaRESUMEN
BACKGROUND: Elevated titers of antibodies against different herpes virus antigens have been reported in some immunodeficient and systemic autoimmune disorders. OBJECTIVE: To examine if Herpes Simplex Virus (HSV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) IgG and IgM antibodies are detected more frequently in children with autoimmune thyroid disease (AITD) compared to controls. SUBJECTS AND METHODS: Thirty-four children with AITD, aged 9.62 +/- 2.35 years, and 31 matched controls, aged 9.24 +/- 2.98 years, were studied. RESULTS: The percentage of EBV IgG+ children with AITD was statistically higher than the percentage of EBV IgG+ controls (82.35% versus 51.61%, P = 0.008). The percentage of EBV IgG+ children with AITD and hypothyroidism was statistically higher than the percentage of EBV IgG+ children with AITD, without hypothyroidism (100% versus 70%, P = 0.024). No other statistically significant differences were observed in HSV-1+2, and CMV IgG or IgM antibodies between the subgroups of children studied. CONCLUSIONS: EBV seroprevalence is higher in children with AITD compared to controls and the underlying pathology remains to be elucidated.
Asunto(s)
Anticuerpos Antivirales/análisis , Herpesviridae/inmunología , Tiroiditis Autoinmune/epidemiología , Tiroiditis Autoinmune/inmunología , Niño , Citomegalovirus/inmunología , Femenino , Bocio/epidemiología , Bocio/inmunología , Bocio/virología , Herpesvirus Humano 4/inmunología , Humanos , Inmunoglobulina G/análisis , Inmunoglobulina M/análisis , Masculino , Estudios Seroepidemiológicos , Tiroiditis Autoinmune/virologíaRESUMEN
BACKGROUND: Thyroid dysfunction (TD) is associated to chronic hepatitis C (HCV) and interferon (IFN) therapy. The prevalence of TD at baseline and during IFN therapy among stages of hepatic fibrosis is unknown. GOALS: To examine the frequency of TD at baseline and during Peg-IFN therapy among patients with severe and mild fibrosis. STUDY: 100 patients were treated with Peg-IFN and divided in 2 groups (50 each), according to liver histology; Metavir 0-2 (mild fibrosis) and Metavir 3-4 (severe fibrosis). Baseline TD was defined as history of TD, or abnormal thyroid stimulating hormone (TSH) or antiperoxidase thyroid auto-antibodies (TPO -Ab). Frequency of TD during therapy was defined as TD that required treatment. RESULTS: 20% in the severe fibrosis group and 10% in the mild fibrosis group, had TD at baseline. Most of the cases, 31.4% were female as compared to 6.25% males. During therapy, 24% of patients in the severe fibrosis group, compared to 12% in the mild fibrosis, had TD. Most patients had biochemical hypothyroidism, and 66% were female, compared to 33.33 % male. TPO-Ab predicted TD during therapy in 50% of cases while those negative only had 16.6% TD during IFN therapy. CONCLUSIONS: Patients with severe fibrosis have more TD events at baseline and during treatment with Peg IFN alfa-2a. Patients with more hepatic fibrosis require careful attention to diagnose and manage TD. More research in the immune mechanisms of hepatic fibrosis progression and autoimmune complications is needed.
Asunto(s)
Hepatitis C Crónica/complicaciones , Cirrosis Hepática/complicaciones , Cirrosis Hepática/virología , Tiroiditis Autoinmune/virología , Antivirales/efectos adversos , Biomarcadores , Femenino , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Humanos , Interferón alfa-2 , Interferón-alfa/efectos adversos , Cirrosis Hepática/epidemiología , Masculino , Persona de Mediana Edad , Polietilenglicoles/efectos adversos , Prevalencia , Proteínas Recombinantes , Índice de Severidad de la Enfermedad , Distribución por Sexo , Tiroiditis Autoinmune/epidemiología , Tiroiditis Autoinmune/inmunologíaRESUMEN
AIM: To demonstrate any differences in the detection of herpes simplex virus type 1 and 2, cytomegalovirus, human herpes virus type 6 and 7 DNA from thyroid tissue blocks of patients with autoimmune thyroid disease and multi-nodular goiter and to propose few mechanisms, which could explain the possible role of herpesvirus infection in the development of thyroid autoimmune responses. MATERIAL-METHODS: Thyroid tissue specimens were obtained postoperatively from 4 patients with multinodular goiter and 18 patients with autoimmune thyroid disease (Graves' disease and Hashimoto thyroiditis). Herpes virus DNA was detected using polymerase chain reaction based assays. RESULTS: No statistically significant differences were observed between autoimmune thyroid disease and multinodular goiter tissue specimens concerning herpes simplex virus type 1, 2 DNA isolation (44.4% vs 0%, P=0.094), human herpes virus type 6 DNA isolation (11.1% vs 0%, P=0.48), human herpes virus type 7 DNA isolation (33.3% vs 25%, P=0.75). No CMV DNA was isolated from any tissue specimen. At least one kind of herpes virus DNA was detected in 13 out of 18 (72.22%) AITD tissue specimens and in 1 out of 4 (25%) MNG tissue specimens (P=0.01). CONCLUSIONS: Although no data are available relating the direct effect of herpes infection on thyroid epithelial cells, a better understanding of how an aberrant immune response against the thyroid gland is initiated and propagated through herpes virus infection is required. Elucidation of the underlying mechanisms may allow the development of new etiologically based therapeutic modalities.
Asunto(s)
ADN Viral/análisis , Herpesviridae/genética , Glándula Tiroides/cirugía , Glándula Tiroides/virología , Tiroiditis Autoinmune/cirugía , Tiroiditis Autoinmune/virología , Bocio Nodular/cirugía , Bocio Nodular/virología , Enfermedad de Graves/cirugía , Enfermedad de Graves/virología , Enfermedad de Hashimoto/cirugía , Enfermedad de Hashimoto/virología , Infecciones por Herpesviridae , Herpesvirus Humano 1/genética , Herpesvirus Humano 2/genética , Herpesvirus Humano 6/genética , Herpesvirus Humano 7/genética , HumanosRESUMEN
Major theories about the etiologies of chronic mental illnesses such as bipolar disorder and schizophrenia include genetic and environmental factors such as famine and infection. It is likely that multiple genes play a role in the pathogenesis of these disorders, but no single gene has been identified as causative. Several viruses have been investigated as potential candidates, but conflicting reports exist. Although a relationship between bipolar disorder and schizophrenia with autoimmune disorders has also been documented for many years, reports are often conflicting. We hypothesize that parvovirus B19 (B19), a common human pathogen, due to its ability to infect the brain and induce autoimmunity, is a strong candidate that may unite prevailing theories. In particular, our preliminary data suggest that B19 may be most likely involved in co-morbid bipolar and autoimmune thyroid disorders in females. In schizophrenics, the gender trend may be reversed. We propose that there is a complex interaction between immuno-genetics, autoimmunity, gender, and B19 infection that leads to at least some forms of bipolar disorder and schizophrenia. Future studies that investigate this hypothesis are warranted and outlined.
Asunto(s)
Encefalitis Viral/virología , Trastornos Mentales/virología , Infecciones por Parvoviridae/virología , Parvovirus B19 Humano , Tiroiditis Autoinmune/virología , Adulto , Encéfalo/virología , Encefalitis Viral/complicaciones , Femenino , Humanos , Masculino , Trastornos Mentales/complicaciones , Persona de Mediana Edad , Modelos Biológicos , Infecciones por Parvoviridae/complicaciones , Factores Sexuales , Tiroiditis Autoinmune/complicacionesRESUMEN
Authors present a case of forty seven years old woman with thrombocytopenia in the course of hepatitis C virus infection. Thrombocytopenia might be related to immunological mechanisms or be an effect of hypersplenism. Moreover mixed cryoglobulinemia, lymphocytic autoimmune thyroiditis with hypothyroidism and other laboratory abnormalities (impaired rate of lymphocytes CD4 to CD8, increase of B cells and natural killer cells, hypocomplementemia, hypergammaglobulinemia, increase of immune complexes concentration) were revealed. Above-mentioned abnormalities might be an effect of hepatitis C virus infection.
Asunto(s)
Crioglobulinemia/virología , Hepatitis C Crónica/complicaciones , Trombocitopenia/virología , Tiroiditis Autoinmune/virología , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/virología , Crioglobulinemia/inmunología , Femenino , Humanos , Persona de Mediana Edad , Trombocitopenia/inmunología , Tiroiditis Autoinmune/inmunologíaRESUMEN
Cytotoxic T-lymphocyte antigen-4 (CTLA-4) decreases the immune response of T cells by inactivating the signal that occurs with interaction between CD28 on T cells and B7 on antigen-presenting cells. Gene polymorphisms involving CTLA-4 promoter (-318 C/T), exon 1 (49 A/G), and exon 4 (microsatellite (AT)n) have been linked to Hashimoto's thyroiditis (HT) and other autoimmune diseases. HT also has a reported association with human T-cell lymphotrophic virus-1 (HTLV-1) infection. We investigated the occurrence of CTLA-4 polymorphisms in Japanese patients with HT with and without anti-HTLV-1 antibodies (HTLV-1 Ab). DNA samples from 143 patients with HT and 199 controls were subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis using the restriction enzymes, Bbv 1, Tse 1, and Mse 1. In the HTLV-1 Ab-positive group the exon 1 G allele was more frequent in patients with HT than in controls (67% vs. 53%, p = 0.0377), and in HTLV-1 Ab-negative group it was also frequent in patients with HT than in controls (68% vs. 53%, p = 0.0041). Frequency of the G allele in HT with HTLV-1 Ab was comparable to those without HTLV-1 Ab. Frequency of polymorphism in the promoter did not differ between patients with HT and controls, nor between controls with and without HTLV-1 Ab. HTLV-1 infection is not associated with CTLA-4 polymorphisms in either HT or controls. HTLV-1 infection is not regulated by genetic factor such as CTLA-4, and may affect occurrence of HT as an independent purely environmental factor.
Asunto(s)
Antígenos de Diferenciación/genética , Infecciones por Deltaretrovirus/inmunología , Virus Linfotrópico T Tipo 1 Humano , Inmunoconjugados , Polimorfismo Genético , Tiroiditis Autoinmune/genética , Tiroiditis Autoinmune/virología , Abatacept , Antígenos CD , Antígeno CTLA-4 , Exones , Femenino , Predisposición Genética a la Enfermedad , Humanos , Japón , Masculino , Regiones Promotoras Genéticas/genética , Tiroiditis Autoinmune/inmunologíaRESUMEN
Hepatitis C virus (HCV) infects mononuclear cells and may, like other viruses, cause immunological disorders. Immunological abnormalities observed in HCV infections are usually nonspecific (e.g. cryoglobulinemia, immune complex deposits, autoantibodies). There is a clear association between cryoglobulinemia and hepatitis C and cryoglobulinemia related symptoms are usually improved by treatment with interferon alpha, although patients usually relapse after treatment end. The relationships between hepatitis C and other immunological abnormalities are unclear. The association between chronic hepatitis C and anti-smooth muscle or anti-nuclear antibodies does not appear to be significantly different from that in other hepatic disorders, particularly hepatitis B. Conversely, patients with hepatitis C have significantly more often anti-liver kidney microsomal (LKM1) antibodies than patients with other causes of liver diseases. When clinical, histological and biological findings are indicative of HCV infection with chronic hepatitis, interferon alpha or combination therapy with ribavirin are treatments options. Conversely, when clinical context and results of laboratory tests are in favor of an autoimmune disorder or of overlap-syndromes (i.e. both autoimmune and viral hepatitis), interferon should not be given in first intention, since revelation or exacerbation of autoimmune hepatitis have been reported under interferon. An important prevalence of anti-HCV antibodies has also been reported in patients with sialadenitis, lichen planus and thyroiditis. It has been clearly demonstrated that interferon may induce or worsen such immunological diseases, but there are very few studies showing improvement of these manifestations under interferon. In conclusion, interferon may be appropriate in patients with HCV infection and extrahepatic manifestations linked to immune complex deposition, whereas, in other cases, careful assessment of patients with autoimmune processes is necessary before choosing any treatment strategy.
Asunto(s)
Enfermedades Autoinmunes/terapia , Hepatitis C Crónica/complicaciones , Antivirales/uso terapéutico , Autoanticuerpos/análisis , Enfermedades Autoinmunes/virología , Crioglobulinemia/terapia , Crioglobulinemia/virología , Hepacivirus/inmunología , Humanos , Enfermedades del Complejo Inmune/terapia , Enfermedades del Complejo Inmune/virología , Interferón-alfa/uso terapéutico , Riñón/inmunología , Riñón/ultraestructura , Liquen Plano/inmunología , Liquen Plano/virología , Microsomas/inmunología , Microsomas Hepáticos/inmunología , Ribavirina/uso terapéutico , Sialadenitis/inmunología , Sialadenitis/virología , Tiroiditis Autoinmune/virologíaAsunto(s)
Hepacivirus/genética , Hepacivirus/patogenicidad , Hepatitis C Crónica/complicaciones , Animales , Crioglobulinemia/virología , Hepatitis C Crónica/inmunología , Humanos , Linfoma/virología , Fibrosis Pulmonar/virología , ARN Viral/sangre , Síndrome de Sjögren/virología , Enfermedades de la Piel/virología , Tiroiditis Autoinmune/virologíaRESUMEN
Lymphoma of thyroid is uncommon, and Epstein-Barr virus (EBV) is found in many lymphomas. We studied the clinicopathologic characteristics in Hong Kong Chinese and analyzed the presence of EBV in thyroid lymphomas by reviewing data collected during 3 decades. We studied EBV gene expression by in situ hybridization and immunohistochemistry. Primary thyroid lymphomas were found in 23 patients (diffuse large B-cell lymphoma, 18; marginal zone B-cell lymphoma, 4; plasmacytoma, 1), and secondary lymphomas were found in 9 patients (diffuse large B-cell lymphoma, 3; Burkitt lymphomas, 2; Burkitt-like lymphoma, 1; hairy cell leukemia, 1; nasal T-cell and natural killer cell lymphoma, 1; and intestinal T-cell lymphoma, 1). Primary thyroid lymphomas were large (mean, 7 cm), found commonly in older women, and often misdiagnosed as undifferentiated carcinomas. Fine-needle aspiration was not helpful for diagnosis. Fifteen patients had Hashimoto thyroiditis. A history of thyrotoxicosis was found in 3 patients, and coexistence of 3 diseases (papillary microcarcinomas, primary thyroid lymphoma, and Hashimoto thyroiditis) was found 4 patients. The 5-year survival rate for primary thyroid lymphoma was 53%. Combined surgery and radiotherapy seemed to be the best treatment. Secondary thyroid lymphomas often were asymptomatic. EBV messenger RNAs were detected in 1 primary and 1 secondary thyroid lymphoma. The EBV gene expression in primary thyroid lymphoma showed a type II latency pattern. Thyroid lymphomas in Chinese had important clinicopathologic features. EBV may have a role in a subset of cases.
Asunto(s)
Infecciones por Herpesviridae/patología , Herpesvirus Humano 4/genética , Linfoma de Células B/patología , Linfoma no Hodgkin/patología , Neoplasias de la Tiroides/patología , Infecciones Tumorales por Virus/patología , Anciano , Anciano de 80 o más Años , Antígenos Virales/análisis , Carcinoma Papilar/patología , Carcinoma Papilar/virología , Femenino , Infecciones por Herpesviridae/complicaciones , Humanos , Técnicas para Inmunoenzimas , Hibridación in Situ , Linfoma de Células B/virología , Linfoma no Hodgkin/virología , Masculino , Persona de Mediana Edad , ARN Mensajero/metabolismo , ARN Viral/análisis , Neoplasias de la Tiroides/virología , Tiroiditis Autoinmune/patología , Tiroiditis Autoinmune/virología , Infecciones Tumorales por Virus/complicacionesRESUMEN
BACKGROUND: Thyroid gland dysfunction has been reported to occur with variable frequency during interferon alfa (IFN-alpha) therapy in patients with the hepatitis C virus (HCV). We prospectively evaluated if the prevalence of autoimmune thyroid disease in patients with HCV differs from that in patients with the hepatitis B virus (HBV) before, at the end of, and 6 months after stopping treatment with IFN-alpha. METHODS: One hundred thirty-four patients with HCV and 41 patients with HBV were studied. Measurements of serum free thyroxine, free triiodothyronine, thyrotropin, thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), and thyrotropin-binding inhibitory immunoglobulin were performed. RESULTS: Positive levels of TPOAb and TgAb were found in 20% and 11% of patients with HCV compared with 5% and 3% of patients with HBV, respectively. At the end of IFN-alpha therapy, thyroid gland dysfunction was more prevalent in patients with HCV (12%) compared with those with HBV (3%), with thyrotropin levels significantly higher in the HCV group (P = .03). Titers of TPOAb, TgAb, and thyrotropin-binding inhibitory immunoglobulin increased significantly (P = .02, P = .04, and P = .02, respectively) at the end of IFN-alpha therapy in patients with HCV but not in those with HBV. Patients who developed thyroid gland dysfunction were predominantly female (P = .03), had decreased levels of free triiodothyronine (P<.001), and had a higher prevalence of TPOAb (P = .03) before treatment with IFN-alpha. Thyroid gland dysfunction was reversed in 60% of those with HCV 6 months after discontinuing treatment with IFN-alpha. CONCLUSIONS: Patients with HCV are more susceptible than patients with HBV to autoimmune thyroid disease. Systematic screening of thyroid gland function and TPOAb titers in all patients with HCV before, during, and after IFN-alpha therapy appears warranted. This precaution is not necessary for patients with HBV.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Tiroiditis Autoinmune/etiología , Adolescente , Adulto , Autoanticuerpos/sangre , Femenino , Hepatitis C/sangre , Humanos , Inmunoglobulinas Estimulantes de la Tiroides , Yoduro Peroxidasa/inmunología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Receptores de Tirotropina/sangre , Riesgo , Tiroglobulina/inmunología , Hormonas Tiroideas/sangre , Tiroiditis Autoinmune/sangre , Tiroiditis Autoinmune/inmunología , Tiroiditis Autoinmune/virologíaRESUMEN
Interferon alpha (IFN-alpha) therapy is associated with a number of immunological side-effects, including autoimmune diseases and a 10% prevalence of thyroiditis. Hepatitis C virus (HCV) infection itself predisposes to autoimmune phenomena including hypothyroidism and myositis. The development of clinical hypothyroidism in the presence of positive thyroid antibodies in patients infected with HCV and treated with IFN-alpha suggests a possible association between the viral disease and the therapy. HCV infection may predispose to autoimmune thyroid disease and IFN-alpha therapy may secondarily lead to the development of thyroid dysfunctions. We report the single case of a female patient who developed a severe proximal myopathy in conjunction with primary hypothyroidism (Hoffmann's syndrome) secondarily to IFN-alpha therapy for HCV infection. This case highlights the need for careful clinical and biological monitoring for potential side-effects in such patients.
Asunto(s)
Hepatitis C Crónica/terapia , Hipotiroidismo/inducido químicamente , Hipotiroidismo/virología , Interferón-alfa/efectos adversos , Adulto , Femenino , Hepatitis C Crónica/diagnóstico , Humanos , Hipotiroidismo/complicaciones , Miositis/etiología , Tiroiditis Autoinmune/inducido químicamente , Tiroiditis Autoinmune/complicaciones , Tiroiditis Autoinmune/virologíaRESUMEN
A high frequency of hepatitis C antibodies has been reported from France in patients with autoimmune thyroiditis. Two cases of Hashimoto's thyroiditis in association with chronic active hepatitis and hepatitis C infection have also been reported. We have examined this potential association in 46 patients with autoimmune hypothyroidism and found that 16 apparently had hepatitis C antibodies in one of the two commercially available enzyme-linked immunosorbent assays (ELISA), but all patients were negative in a confirmatory commercially available recombinant immunoblot assay (RIBA-3) indicating that none of the patients were truly positive for hepatitis C antibodies. We also tested sera from 111 patients with proven hepatitis C infection and found no increased prevalence of thyroid autoantibodies. These results suggest that hepatitis C infection is not a risk factor for the development of thyroid autoimmunity in the United Kingdom.