RESUMO
OBJECTIVE: Identify molecular mimicry between TPO, eosinophil peroxidase (EPX), thyroglobulin and IL24 and microorganism antigens. METHODS: Through in silico analysis, we performed local alignments between human and microorganism antigens with PSI-BLAST. Proteins that did not present a 3D structure were modeled by homology through the Swiss Modeller server and epitope prediction was performed through Ellipro. Epitopes were located in the 3D models using PYMOL software. RESULTS: A total of 38 microorganism antigens (parasites, bacteria) had identities between 30% and 45%, being the highest with Anisakis simplex. The alignment between 2 candidate proteins from A. simplex and EPX presented significant values, with identities of 43 and 44%. In bacteria, Campylobacter jejuni presented the highest identity with thyroglobulin (35%). 220 linear and conformational epitopes of microorganism antigens were predicted. Peroxidasin-like proteins from Toxocara canis and Trichinella pseudospiralis presented 10 epitopes similar to TPO and EPX, as possible molecules triggering cross-reactivity. No virus presented identity with the human proteins studied. CONCLUSION: TPO and EPX antigens shared potential cross-reactive epitopes with bacterial and nematode proteins, suggesting that molecular mimicry could be a mechanism that explains the relationship between infections and urticaria/hypothyroidism. In vitro work is needed to demonstrate the results obtained in the in silico analysis.
OBJETIVO: Identificar mimetismo molecular entre TPO, eosinofil peroxidasa (EPX), tiroglobulina e IL24 y antígenos de microorganismos. MÉTODOS: A través de análisis in silico, realizamos los alineamientos locales entre los antígenos humanos y de microorganismos con PSI-BLAST. Las proteínas que no presentaban estructura 3D, fueron modeladas por homología a través del servidor Swiss Modeller y se realizó una predicción de epítopes a través de Ellipro. Los epítopes se localizaron en los modelos 3D utilizando el software PYMOL. RESULTADOS: Un total de 38 antígenos de microorganismos (parásitos y bacterias), tuvieron identidades entre 30 y 45%, siendo los más altos con Anisakis simplex. El alineamiento entre dos proteínas candidatas de A. simplex y EPX presentaron valores importantes, con identidades de 43 y 44%. En las bacterias, Campylobacter jejuni presentó la mayor identidad con tiroglobulina (35%). Se predijeron 220 epítopes lineales y conformacionales de antígenos de microorganismos. Las proteínas similares a la peroxidasina de Toxocara canis y Trichinella pseudospiralis presentaron diez epítopes similares a TPO y EPX, como posibles moléculas desencadenantes de una reactividad cruzada. Ningún virus presentó identidad con las proteínas humanas estudiadas. CONCLUSIÓN: Los antígenos TPO y EPX compartieron potenciales epítopes de reacción cruzada con proteínas bacterianas y nematodos, lo que sugiere que el mimetismo molecular podría ser un mecanismo que explique la relación entre infecciones y la urticaria/hipotiroidismo. Se necesitan trabajos in vitro que demuestren los resultados obtenidos en el análisis in silico.
Assuntos
Autoantígenos , Iodeto Peroxidase , Mimetismo Molecular , Tireoglobulina , Mimetismo Molecular/imunologia , Humanos , Tireoglobulina/imunologia , Iodeto Peroxidase/imunologia , Peroxidase de Eosinófilo/imunologia , Animais , Antígenos de Bactérias/imunologia , Reações Cruzadas , Proteínas de Ligação ao Ferro/imunologia , Epitopos/imunologiaRESUMO
BACKGROUND: Human proteins such as interleukin-24 (IL24), thyroperoxidase (TPO) and thyroglobulin (Tg) are targets of IgE or IgG autoantibodies. Why these proteins are recognized by autoantibodies in some patients with chronic spontaneous urticaria (CSU) or hypothyroidism is unknown. OBJECTIVE: Through in silico analysis, identify antigen patches of TPO, Tg and IL24 and compare the sequences of these human proteins with some prevalent allergens. METHODS: The amino acids sequences of IL24, thyroperoxidase and thyroglobulin were compared between them and with 22 environmental allergens. Phylogenetic studies and multiple pairing were carried out to explore the degree of protein identity and cover. The proteins without 3D structure reported in the database, were modeled by homology with "Swiss Modeller" and compared through PYMOL. Residues conserved and accessible to the solvent (rASA> 0.25) were located in the 3D model to identify possible areas of cross-reactivity and antigen binding. RESULTS: We build a 3D model of the TPO and thyroglobulin protein base on proteins closely related. Five epitopes for TPO, six for IL24 and six for thyroglobulin were predicted. The amino acid sequences of allergens from different sources (Dermatophagoides pteronyssinus, Blomia tropicalis, Betula verrucosa, Cynodon dactylon, Aspergillus fumigatus, Canis domesticus, Felis domesticus) were compared with human TPO, Tg and IL24. The cover and alignments between allergens and human proteins were low. CONCLUSION: We identify possible linear and conformational epitopes of TPO, Tg and IL24 that could be the target of IgE or IgG binding in patients with urticaria or hypothyroidism; These epitopes do not appear to be present among common environmental allergens, suggesting that autoreactivity to these human proteins are not by cross-reactivity.
Assuntos
Alérgenos/imunologia , Autoantígenos/imunologia , Urticária Crônica/imunologia , Epitopos/imunologia , Hipotireoidismo/imunologia , Interleucinas/imunologia , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Tireoglobulina/imunologia , Animais , Aspergillus fumigatus/imunologia , Autoanticorpos/imunologia , Autoantígenos/química , Autoantígenos/classificação , Gatos , Reações Cruzadas , Cães , Mapeamento de Epitopos , Epitopos/química , Epitopos/classificação , Humanos , Interleucinas/química , Interleucinas/classificação , Iodeto Peroxidase/química , Iodeto Peroxidase/classificação , Proteínas de Ligação ao Ferro/química , Proteínas de Ligação ao Ferro/classificação , Modelos Químicos , Filogenia , Tireoglobulina/química , Tireoglobulina/classificaçãoRESUMO
BACKGROUND: Chronic spontaneous urticaria (CSU) is a heterogeneous disease with some frequent comorbidities like autoimmune diseases, drug reactions, and inducible urticaria. IgE antibodies against thyroid peroxidase (anti-TPO IgE) could be associated with some of these clinical characteristics. OBJECTIVE: To explore the clinical characteristics of CSU patients, according to the presence of anti-TPO IgE in serum. METHODS: Anti-TPO IgE levels were measured during the clinical control period (Urticaria Activity Score, 0 point) and exacerbation period (≥3 points) in 100 CSU patients. Patients with self-reported exacerbation of skin involvement by foods, nonsteroidal anti-inflammatory drugs (NSAIDs), and physical triggers underwent controlled challenge tests. RESULTS: We identified 2 groups of patients: (1) patients with anti-TPO IgE during the clinical control period or during an exacerbation, who had a higher frequency of atopy, asthma, and positive challenge test results with NSAIDs and (2) patients without anti-TPO IgE during any period, who had a higher frequency of positive challenge test results for inducible urticaria. Among the first group (anti-TPO IgE at any point), we identified 3 subgroups: patients with anti-TPO IgE during the clinical control period (n = 12); patients with anti-TPO IgE during the clinical control period and significantly increased levels during an urticaria exacerbation (n = 18); and patients with anti-TPO IgE only during an exacerbation (n = 13). None of the patients with self-reported food reactions had a positive challenge test result. CONCLUSION: Anti-TPO IgE is a useful biomarker for differentiating between clinical phenotypes of patients with CSU. Elevation of anti-TPO IgE during exacerbation periods supports an association between this autoantibody and the pathogenesis of urticaria.
Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Urticária Crônica/diagnóstico , Urticária Crônica/etiologia , Imunoglobulina E/imunologia , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Adolescente , Adulto , Autoanticorpos/sangue , Biomarcadores , Suscetibilidade a Doenças/imunologia , Feminino , Humanos , Imunoglobulina E/sangue , Masculino , Pessoa de Meia-Idade , Adulto JovemAssuntos
Hipotireoidismo/tratamento farmacológico , Tireotropina/sangue , Tiroxina/administração & dosagem , Adulto , Autoantígenos/imunologia , Feminino , Humanos , Hipotireoidismo/sangue , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Suspensão de Tratamento , Adulto JovemRESUMO
BACKGROUND: Understanding the etiopathogenesis of chronic spontaneous urticaria (CSU) remains a challenge. The clinical and laboratory characteristics relating to its histocompatibility profile and autoimmunity are constant research topics. OBJECTIVES: To analyze the clinical and laboratory characteristics of patients with CSU by means of a cross-sectional study, focusing on the histocompatibility profile, presence of antinuclear antibodies (ANA) and presence of antithyroperoxidase antibodies (anti-TPO). MATERIALS & METHODS: Sixty-seven adults with CSU were analyzed. The autologous serum skin test (ASST), ANA and anti-TPO were performed in all cases and MHC classes I and II (loci A, B and DR) were evaluated in 49 patients. RESULTS: The factors that worsened urticaria included use of non-steroid anti-inflammatory drugs, emotional stress and physical stimuli, reported by 27%, 16% and 15% of these patients, respectively. The ASST test was positive in 49 patients (73%) and anti-TPO and ANA were present in 15 (22.4%) and 7 (10.5%), respectively. The OR (with 95% CI) for the association between ANA and anti-TPO was 5.94 (1.16-30.42), and thus statistically significant. There was a favorable association (with statistical significance) between HLA B*50 and patients with CSU, with OR (95% CI) of 2.96 (1.17- 7.48). CONCLUSION: A significant favorable association was found between these patients and HLA B*50, and between the presence of anti-TPO and ANA. The greater prevalence of HLA B*50 in these patients and the association between ANA and anti-TPO reinforce the possibility that an immunogenic mechanism may be the triggering factor for CSU.
Assuntos
Antígenos HLA-B/metabolismo , Urticária/epidemiologia , Urticária/imunologia , Adulto , Anti-Inflamatórios não Esteroides , Anticorpos Antinucleares/sangue , Autoantígenos/imunologia , Brasil , Doença Crônica , Estudos Transversais , Feminino , Antígenos HLA-B/genética , Antígenos HLA-B/imunologia , Histocompatibilidade/genética , Teste de Histocompatibilidade , Humanos , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Masculino , Prevalência , Fatores de Risco , Testes Cutâneos , Estresse Psicológico , Urticária/genéticaRESUMO
OBJECTIVES: The general purpose of this study is to assess the distribution among the various hormonal indices in young pregnant women with negative thyroid peroxidase antibodies and iodine sufficiency and classify them accordingly while comparing them to literature proposed reference values for the first trimester. METHODS: A sectional study was carried out, including 127 pregnant women enrolled at the prenatal outpatient clinic at the Nova Iguaçu General Hospital, in the period comprised between 2000 and June 2007. They were submitted to TSH, free T(4), total T(4), TBG, and thyroid peroxidase antibody determinations. RESULTS: A median equal to 38.7 microg/ml was observed for TBG; TSH values varied between 0.02 and 5.84 mcUI/ml, with a median of 1.25 mcUI/ml. For total T(4) and free T(4), median values were, respectively 10.3 microg/dl and 1.20 ng/dl. Thirteen patients out of 115 displayed a TSH serum level above 2.5 mUI/ml. CONCLUSIONS: Patients with subclinical hypothyroidism classified by this new cutoff (serum TSH concentration between 2.5 mUI/l and the upper limit of the reference range), chiefly ATPO-negative young women display no need for treatment as there is no evidence that this condition is associated with maternal and fetal complications.
Assuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Primeiro Trimestre da Gravidez/sangue , Tireotropina/sangue , Adulto , Doenças Autoimunes/sangue , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Estudos Transversais , Técnicas de Diagnóstico Endócrino/normas , Feminino , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/complicações , Hipotireoidismo/diagnóstico , Concentração Osmolar , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/diagnóstico , Valores de Referência , Tireotropina/normas , Adulto JovemRESUMO
The aim of this study was to evaluate the frequency of thyroid dysfunction and thyroid antibodies in patients with juvenile onset Systemic Lupus Erythematosus (JOSLE) and its association with clinical and immunological features. Seventy-seven patients with JOSLE, 64 females, median age 19 years, were consecutively enrolled from March to December 2007. Clinical data related to thyroid dysfunction and lupus were obtained by chart review and patient interview. Serum levels of TSH, free T4, anti-thyroglobulin (TgAb), anti-thyroperoxidase (TPOAb), TRAb and lupus related autoantibodies were analyzed by standard techniques. Nine patients were diagnosed as hypothyroidism and 4 hyperthyroidism. 28% JOSLE patients had moderate/high titer of thyroid antibodies: 23% TgAb, 2.6% TPOAb and 3.9% TRAb. JOSLE patients with positive thyroid autoantibodies had higher frequency of anti-U1RNP antibodies than patients without these antibodies (40.9 vs. 14.5%, OR:0.25, CI:0.08-0.76, p = 0.017). Furthermore, renal/neurological/hematological involvement was less frequently observed in patients with hypothyroidism (55.6 vs. 87.5%, OR:0.18, CI:0.04-0.81, p = 0.035) and with thyroid antibodies (68.4 vs. 90.9%, OR:0.22, CI:0.06-0.82, p = 0.027) than in patients without these alterations. No association with PTPN22 polymorphism was found. In conclusion, JOSLE patients have high prevalence of subclinical hypothyroidism. The novel association of anti-thyroid antibodies with anti-U1RNP antibodies in JOSLE seems to identify a subgroup of patients with less life-threatening organ involvement.
Assuntos
Autoanticorpos/sangue , Lúpus Eritematoso Sistêmico/complicações , Doenças da Glândula Tireoide/imunologia , Adolescente , Adulto , Autoantígenos/imunologia , Criança , Feminino , Genótipo , Humanos , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Lúpus Eritematoso Sistêmico/genética , Masculino , Polimorfismo de Nucleotídeo Único/genética , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Proteína Tirosina Fosfatase não Receptora Tipo 22/imunologia , Proteína Tirosina Fosfatase não Receptora Tipo 22/metabolismo , Receptores da Tireotropina/imunologia , Ribonucleoproteína Nuclear Pequena U1/sangue , Doenças da Glândula Tireoide/genética , Tireotropina/sangue , Tiroxina/sangue , Adulto JovemRESUMO
BACKGROUND: Clinical repercussions, progression to overt hypothyroidism, and treatment benefits have been well established in patients with subclinical hypothyroidism (SCH) and TSH >10 mIU/L. In contrast, these aspects of the disease are poorly understood in patients with even milder SCH as defined by TSH < or = 10 mIU/L and normal thyroid hormone levels. Therefore, we sought to evaluate the natural history of this milder form of SCH (TSH < or =10 mIU/L with normal thyroid hormone levels) in adult women patients. PATIENTS: One hundred seventeen patients with TSH levels ranging from 5 to 10 mIU/L and normal free T4, without a previously known history of thyroid disease, were followed for a period of 3 years and had two consecutive assessments. RESULTS: Sixty patients tested positive for antithyroperoxidase antibodies (TPOAb) and 36 were TPOAb negative but had diffuse hypoechogenicity on thyroid ultrasound (US). Twenty-one patients were TPOAb negative and had normal US. During follow-up, 20.5% of the patients had spontaneous normalization of their TSH, 27.3% required replacement therapy with levothyroxine (L-T4) because of progression to overt hypothyroidism or persistence of serum TSH >10 mIU/L, and 52.1% continued to meet the criteria for mild SCH (persistence of TSH < or =10 mIU/L). If the patients were classified into two groups, one with positive TPOAb and/or US alteration and the other with testing negative for TPOAb and not having US alteration, the first group had a greater progression toward overt hypothyroidism (31.2% vs. 9.5%, respectively) and a lower rate of normalization of TSH (15.6% vs. 43% respectively). These rates were similar in TPOAb-positive patients and patients with negative TPOAb but with positive US. CONCLUSIONS: Most patients with SCH and TSH < or = 10 mIU/L do not progress to overt hypothyroidism. The presence of chronic thyroiditis as demonstrated by US increases the evolution of SH to overt hypothyroidism or more severe SCH and thus the need for L-T4 treatment. US findings are important in determining the prognosis of mild SCH.
Assuntos
Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico por imagem , Tireotropina/sangue , Adulto , Anticorpos Anti-Idiotípicos/sangue , Autoantígenos/imunologia , Progressão da Doença , Feminino , Humanos , Hipotireoidismo/tratamento farmacológico , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Tiroxina/uso terapêutico , UltrassonografiaRESUMO
PROBLEM: To investigate the utility of thyroid peroxidase antibodies (TPOAb) in early pregnancy combined with clinical information for prediction of postpartum thyroid dysfunction (PPTD) within 1 year postpartum. METHOD OF STUDY: We studied 98 pregnant women by determining their TPOAb levels in early pregnancy, as well as their serum thyrotropin and free thyroid (fT4) levels at 6 and 12 months postpartum. Furthermore, they answered a questionnaire and physical examination was performed by only one examiner. RESULTS: Of the 98 women, 10 were positive TPOAb in early pregnancy. The overall risk of PPTD within 1 year of follow-up was 10.2% (95% CI 4.1-16.3). Risk of PPTD was significantly higher among women with a family history of thyroid disease, TPOAb positive and presenting goiter in early pregnancy. The sensitivity, specificity and positive predictive value of TPOAb in PPTD prediction were 60.0%, 95.5% and 60%. Restricting screening to women with a family history of thyroid disease or presenting goiter increases the positive predictive value from 60% to 82.4%. CONCLUSION: Our results suggest that TPOAb could be used as a screening test for PPTD prediction at least among women who present a high risk of developing PPTD.
Assuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Programas de Rastreamento/métodos , Período Pós-Parto/sangue , Doenças da Glândula Tireoide/diagnóstico , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Valor Preditivo dos Testes , Gravidez , Primeiro Trimestre da Gravidez/imunologia , Medição de Risco , Fatores de Risco , Sensibilidade e Especificidade , Inquéritos e Questionários , Doenças da Glândula Tireoide/sangue , Doenças da Glândula Tireoide/etiologia , Doenças da Glândula Tireoide/imunologia , Tireotropina/sangue , Tiroxina/sangue , Fatores de TempoRESUMO
Among bullous diseases, pemphigus vulgaris (PV) is a classical variety of this type of skin disorders. To establish the real prevalence of thyroid abnormalities in such a disease, a prospective study was developed. For this reason, thyroid evaluation was performed in 15 consecutive patients who attended the Dermatology Clinic for PV and in a group of 15 healthy volunteers (Control Group) matched by age and gender. Thyroid function was evaluated by measuring T3, T4 and TSH. The presence or absence of goiter was searched by palpation, while thyroid autoimmunity was investigated through the assay of thyroperoxidase antibodies (TPO-Ab). In each group there were 9 women and 6 men, aging 25-65 years (mean = 48.3 y) in the PV Group, and 25-69 years (mean = 45.4 y) in the Control Group. It was found that 7 patients (46.6%) of the PV Group and 1 subject (6.7%) of the Control Group (p < 0.015) disclosed thyroidal alterations. Positive titers of TPO-Ab were observed in 6 patients with PV and in one volunteer. Goiter and subclinical hypothyroidism were found in one PV patient with negative TPO-Ab. Out of the total 7 cases with positive TPO-Ab, only a PV patient had an overt Hashimoto's thyroiditis. All other cases had only the presence of thyroid auto-antibodies without clinical evidences of chronic thyroiditis. It is concluded that PV is highly associated with primary thyroid disorders, mainly with positive titers of TPO-Ab, although most patients do not present overt clinical thyroid disease.