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1.
Int J Mol Sci ; 22(6)2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33802091

RESUMO

Since 2015, 170 small molecules, 60 antibody-based entities, 12 peptides, and 15 gene- or cell-therapies have been approved by FDA for diverse disease indications. Recent advancement in medicine is facilitated by identification of new targets and mechanisms of actions, advancement in discovery and development platforms, and the emergence of novel technologies. Early disease detection, precision intervention, and personalized treatments have revolutionized patient care in the last decade. In this review, we provide a comprehensive overview of current and emerging therapeutic modalities developed in the recent years. We focus on nine diseases in three major therapeutics areas, diabetes, autoimmune, and neurological disorders. The pathogenesis of each disease at physiological and molecular levels is discussed and recently approved drugs as well as drugs in the clinic are presented.


Assuntos
Doenças Autoimunes/terapia , Diabetes Mellitus/terapia , Doenças do Sistema Nervoso/terapia , Doenças Autoimunes/patologia , Diabetes Mellitus/patologia , Humanos , Doenças do Sistema Nervoso/patologia
2.
Int J Mol Sci ; 22(7)2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33810246

RESUMO

Autoimmune disease development depends on multiple factors, including genetic and environmental. Abnormalities such as sialylation levels and/or quality have been recently highlighted. The adjunction of sialic acid at the terminal end of glycoproteins and glycolipids is essential for distinguishing between self and non-self-antigens and the control of pro- or anti-inflammatory immune reactions. In autoimmunity, hyposialylation is responsible for chronic inflammation, the anarchic activation of the immune system and organ lesions. A detailed characterization of this mechanism is a key element for improving the understanding of these diseases and the development of innovative therapies. This review focuses on the impact of sialylation in autoimmunity in order to determine future treatments based on the regulation of hyposialylation.


Assuntos
Autoanticorpos/metabolismo , Doenças Autoimunes/imunologia , Processamento de Proteína Pós-Traducional , Ácidos Siálicos/metabolismo , Animais , Autoanticorpos/imunologia , Doenças Autoimunes/terapia , Humanos , Imunofenotipagem/métodos , Medicina de Precisão/métodos , Ácidos Siálicos/imunologia
3.
BMJ Case Rep ; 14(4)2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849864

RESUMO

The COVID-19 pandemic caused by the SARS-CoV-2 virus has affected millions of people around the globe. The most common presentation of COVID-19 is fever and upper and lower respiratory tract infection. Myalgia is fairly common in the prodromal phase of the viral illness which self-resolves. There is very scant literature on autoimmune myositis triggered by COVID-19 infection. We report a case of SARS-CoV-2 infection, who presented with progressive muscle weakness with rhabdomyolysis and necrotizing autoimmune myopathy on muscle biopsy. This case report imposes awareness of musculoskeletal autoimmune processes triggered by COVID-19 which requires clinical suspicion for early diagnosis and initiation of treatment.


Assuntos
Doenças Autoimunes/virologia , Miosite/virologia , Anticorpos Antivirais/sangue , Doenças Autoimunes/terapia , Diagnóstico Diferencial , Feminino , Humanos , Imunoglobulina G/sangue , Pessoa de Meia-Idade , Debilidade Muscular/virologia , Mialgia/virologia , Miosite/terapia , Necrose/virologia , Prednisona/uso terapêutico , Rabdomiólise/virologia
5.
Zhonghua Nei Ke Za Zhi ; 60(3): 192-206, 2021 Mar 01.
Artigo em Chinês | MEDLINE | ID: mdl-33663167

RESUMO

IgG4 related disease (IgG4-RD) is an immune medicated rare disease, characterized with chronic inflammation and fibrosis in the involved organs, it is a systemic disease affected nearly every anatomic site of the body, usually involvement of multiple organs, and with diverse clinical manifestations. Due to the the relative novelty of the disease and under-recognition, the overall level of diagnosis and treatment in China is uneven. Till now, there is no relevant expert consensus or guidance of IgG4-RD in China. In order to further improve the understanding and standardize the management of IgG4-RD, on the basis of summarizing domestic and international experience, the China Alliance For Rare Diseases, together with the Chinese Rheumatology Association, organized an expert group and established the Chinese expert consensus on the diagnosis and treatment of IgG4 related diseases.


Assuntos
Doenças Autoimunes , Reumatologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/terapia , China , Consenso , Fibrose , Humanos , Imunoglobulina G
6.
Hautarzt ; 72(4): 277-287, 2021 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-33646324

RESUMO

Paraneoplastic skin manifestations associated with malignancies are extremely polymorphous. Clinicians should be familiar with paraneoplastic dermatoses to establish an early diagnosis of the underlying neoplasm. Lack of familiarity with cutaneous clues for internal malignancies may delay diagnosis and treatment of cancer. In this review, we describe several paraneoplastic autoimmune dermatoses, including paraneoplastic autoimmune multiorgan syndrome, paraneoplastic bullous pemphigoid, and paraneoplastic dermatomyositis.


Assuntos
Doenças Autoimunes , Síndromes Paraneoplásicas , Penfigoide Bolhoso , Dermatopatias , Autoanticorpos , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/terapia , Humanos , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/terapia
8.
Am J Chin Med ; 49(2): 237-268, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33622213

RESUMO

Intestinal flora is essential for maintaining host health and plays a unique role in transforming Traditional Chinese Medicine (TCM). TCM, as a bodyguard, has saved countless lives and maintained human health in the long history, especially in this COVID-19 pandemic. Pains of diseases have been removed from the effective TCM therapy, such as TCM preparation, moxibustion, and acupuncture. With the development of life science and technology, the wisdom and foresight of TCM has been more displayed. Furthermore, TCM has been also inherited and developed in innovation to better realize the modernization and globalization. Nowadays, intestinal flora transforming TCM and TCM targeted intestinal flora treating diseases have been important findings in life science. More and more TCM researches showed the significance of intestinal flora. Intestinal flora is also a way to study TCM to elucidate the profound theory of TCM. Processing, compatibility, and properties of TCM are well demonstrated by intestinal flora. Thus, it is no doubt that intestinal flora is a core in TCM study. The interaction between intestinal flora and TCM is so crucial for host health. Therefore, it is necessary to sum up the latest results in time. This paper systematically depicted the profile of TCM and the importance of intestinal flora in host. What is more, we comprehensively summarized and discussed the latest progress of the interplay between TCM and intestinal flora to better reveal the core connotation of TCM.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Disbiose/microbiologia , Microbioma Gastrointestinal , Medicina Tradicional Chinesa , Doenças Autoimunes/microbiologia , Doenças Autoimunes/terapia , Doenças Cardiovasculares/microbiologia , Doenças Cardiovasculares/terapia , Diabetes Mellitus/microbiologia , Diabetes Mellitus/terapia , Eletroacupuntura , Gastroenteropatias/microbiologia , Gastroenteropatias/terapia , Humanos , Doenças Metabólicas/microbiologia , Doenças Metabólicas/terapia , Neoplasias/microbiologia , Neoplasias/terapia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Obesidade/microbiologia , Obesidade/terapia , Insuficiência Renal Crônica/microbiologia , Insuficiência Renal Crônica/terapia
9.
Adv Exp Med Biol ; 1278: 257-272, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33523452

RESUMO

The puzzling biphasic or dual roles of tumor necrosis factor α (TNF) in the inflammatory and immune responses are likely to be mediated by distinct signaling pathways transduced by one of its two receptors, e.g., TNF receptor type I (TNFR1) and TNF receptor type II (TNFR2). Unlike TNFR1 that is ubiquitously expressed on almost all types of cells, the expression of TNFR2 is rather restricted to certain types of cells, such as T lymphocytes. There is now compelling evidence that TNFR2 is preferentially expressed by CD4+Foxp3+ regulatory T cells (Tregs), and TNFR2 plays a decisive role in the activation, expansion, in vivo function, and phenotypical stability of Tregs. In this chapter, the current understanding of the molecular basis and signaling pathway of TNF-TNFRs signal is introduced. Latest studies that have further supported and substantiated the pivotal role of TNF-TNFR2 interaction in Tregs biology and its molecular basis are discussed. The research progress regarding TNFR2-targeting treatment for autoimmune diseases and cancer is analyzed. Future study should focus on the further understanding of molecular mechanism underlying Treg-stimulatory effect of TNFR2 signal, as well as on the translation of research findings into therapeutic benefits of human patients with autoimmune diseases, allergy, allograft rejection, and cancer.


Assuntos
Doenças Autoimunes , Neoplasias , Doenças Autoimunes/terapia , Fatores de Transcrição Forkhead/genética , Humanos , Neoplasias/terapia , Receptores Tipo II do Fator de Necrose Tumoral/genética , Linfócitos T Reguladores , Fator de Necrose Tumoral alfa/genética
10.
Adv Exp Med Biol ; 1278: 191-203, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33523449

RESUMO

Autoimmune conditions affect 23 million Americans or 7% of the US population. There are more than 100 autoimmune disorders, affecting every major organ system in humans. This chapter aims to further explain Treg dysfunction autoimmune disorders, including monogenic primary immune deficiency such as immune dysregulation polyendocrinopathy, enteropathy, X-linked inheritance (IPEX) syndrome, and polygenic autoimmune diseases with Treg dysfunction such as multiple sclerosis (MS), inflammatory bowel disease (IBD), and food allergy. These conditions are associated with an abnormal small intestinal and colonic microbiome. Some disorders clearly improve with therapies aimed at microbial modification, including probiotics and fecal microbiota transplantation (FMT). Approaches to prevent and treat these disorders will need to focus on the acquisition and maintenance of a healthy colonic microbiota, in addition to more focused approaches at immune suppression during acute disease exacerbations.


Assuntos
Doenças Autoimunes , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Doenças Autoimunes/terapia , Disbiose , Transplante de Microbiota Fecal , Humanos , Linfócitos T Reguladores
11.
Int J Mol Sci ; 22(3)2021 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-33498928

RESUMO

Immunomodulation is on the cusp of being an important therapy for treating many diseases, due to the significant role of the immune system in defending the human body. Although the immune system is an essential defense system, overactivity can result in diverse sicknesses such as inflammation and autoimmune disease. Exosomes are emerging as a state-of-the-art therapeutic strategy for treating an overactive immune system. Thus, exosomes have drawn great interest for their potential clinical applications in treating diseases associated with abnormal immune regulation. Hence, in this review, we will discuss trends in exosome research related to inflammatory and autoimmune diseases. Possible therapeutic applications of exosomes will be summarized. Finally, an outlook to the future of exosomal therapy will be introduced.


Assuntos
Doenças Autoimunes/terapia , Exossomos , Imunomodulação , Inflamação/terapia , Animais , Humanos
12.
Autoimmun Rev ; 20(3): 102761, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33476816

RESUMO

Regulatory T cells (Tregs) are a subset of T cells responsible for the regulation of immune responses, thereby maintaining immune homeostasis and providing immune tolerance to both self and non-self-antigens. An increasing number of studies revealed Treg numbers and functions in a variety of autoimmune diseases. Treg deficiency can cause the development of several autoimmune skin diseases including vitiligo, alopecia areata, pemphigoid and pemphigus, psoriasis, and systemic sclerosis. Many clinical trials have been performed for autoimmune conditions using polyclonal Tregs, but efficiency can be significantly improved using antigen-specific Tregs engineered using T cell receptor (TCR) or chimeric antigen receptor (CAR) constructs. In this review, we systematically reviewed altered frequencies, impaired functions, and phenotypic features of Tregs in autoimmune skin conditions. We also summarized new advances in TCR and CAR based antigen-specific Tregs tested both in animal models and in clinics. The advantages and limitations of each approach were carefully discussed emphasizing possible clinical relevance to patients with autoimmune skin diseases. Moreover, we have reviewed potential approaches for engineering antigen-specific Tregs, and strategies for overcoming possible hurdles in clinical applications. Thereby, antigen-specific Tregs can be infused using autologous adoptive cell transfer to restore Treg numbers and to provide local immune tolerance for autoimmune skin disorders.


Assuntos
Doenças Autoimunes , Dermatopatias , Animais , Doenças Autoimunes/terapia , Humanos , Tolerância Imunológica , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T Reguladores
13.
Autoimmun Rev ; 20(2): 102738, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33326854

RESUMO

Autoimmune diseases (AIDs) share similar serological, clinical, and radiological findings, but, behind these common features, there are different pathogenic mechanisms, immune cells dysfunctions, and targeted organs. In this context, multiple lines of evidence suggest the application of precision medicine principles to AIDs to reduce the treatment failure. Precision medicine refers to the tailoring of therapeutic strategies to the individual characteristics of each patient, thus it could be a new approach for management of AIDS which considers individual variability in genes, environmental exposure, and lifestyle. Precision medicine would also assist physicians in choosing the right treatment, the best timing of administration, consequently trying to maximize drug efficacy, and, possibly, reducing adverse events. In this work, the growing body of evidence is summarized regarding the predictive factors for drug response in patients with AIDs, applying the precision medicine principles to provide high-quality evidence for therapeutic opportunities in improving the management of these patients.


Assuntos
Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Síndrome de Sjogren , Doenças Autoimunes/terapia , Consenso , Humanos , Medicina de Precisão
14.
Nat Nanotechnol ; 16(1): 37-46, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33349685

RESUMO

Induced tolerogenic dendritic cells are a powerful immunotherapy for autoimmune disease that have shown promise in laboratory models of disease and early clinical trials. In contrast to conventional immunosuppressive treatments, tolerogenic immunotherapy leverages the cells and function of the immune system to quell the autoreactive lymphocytes responsible for damage and disease. The principle techniques of isolating and reprogramming dendritic cells (DCs), central to this approach, are well characterized. However, the broader application of this technology is limited by its high cost and bespoke nature. Nanomedicine offers an alternative route by performing this reprogramming process in situ. Here, we review the challenges and opportunities in using nanoparticles as a delivery mechanism to target DCs and induce immunomodulation, emphasizing their versatility. We then highlight their potential to solve critical problems in organ transplantation and increasingly prevalent autoimmune disorders such as type 1 diabetes mellitus and multiple sclerosis, where new immunotherapy approaches have begun to show promise.


Assuntos
Células Dendríticas/imunologia , Sistemas de Liberação de Medicamentos/métodos , Nanomedicina/métodos , Nanopartículas , Tolerância ao Transplante/imunologia , Animais , Antígenos/imunologia , Doenças Autoimunes/terapia , Humanos , Imunomodulação , Imunossupressores/administração & dosagem , Nanopartículas/química , Tamanho da Partícula
15.
Rev. Hosp. Ital. B. Aires (2004) ; 40(4): 199-207, dic. 2020. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-1145501

RESUMO

La encefalitis límbica es una enfermedad infrecuente y potencialmente grave, que puede o no ser paraneoplásica y se caracteriza por déficit de la memoria reciente, alteraciones psiquiátricas y convulsiones. De origen autoinmunitario, está asociada a anticuerpos séricos e intratecales contra antígenos neuronales intracelulares y de superficie, con especial afectación de zonas límbicas. En este artículo se revisan aspectos históricos y epidemiológicos, patogenia, síndromes más frecuentes y mejor delimitados, histopatología y estudios complementarios. Se repasan también las dificultades del diagnóstico diferencial y la necesidad de descartar siempre un tumor subyacente. La detección de autoanticuerpos neuronales es importante para el diagnóstico, la planificación terapéutica y el pronóstico. La inmunoterapia y, si corresponde, el tratamiento de la neoplasia son cruciales para lograr una recuperación neurológica sustancial. La encefalitis límbica es una entidad probablemente subdiagnosticada, con un pronóstico más favorable si se trata de forma temprana. El actual conocimiento de su patogenia puede además aportar claridad para la mejor comprensión de otros síndromes neurológicos y psiquiátricos que puedan compartir mecanismos autoinmunitarios, como algunos trastornos psicóticos y epilepsias farmacorresistentes. (AU)


Limbic encephalitis is a rare and potentially serious disease, which may or may not be paraneoplastic and is characterized by recent memory deficits, psychiatric disturbances and seizures. Of autoimmune origin, it is associated with serum and intrathecal antibodies against intracellular and surface neuronal antigens, with special involvement of limbic areas. This article reviews historical and epidemiological aspects, pathogenesis, more frequent and better defined syndromes, histopathology and complementary studies. The difficulties of differential diagnosis and the need to always rule out an underlying tumor are also reviewed. Detection of neuronal autoantibodies is important for diagnosis, therapeutic planning and prognosis. Immunotherapy and, if appropriate, neoplasm treatment, are crucial to achieve substantial neurological recovery. Limbic encephalitis is probably an underdiagnosed entity, with a more favorable prognosis if treated early. The current knowledge of its pathogenesis may also provide clarity for a better understanding of other neurological and psychiatric syndromes that may share autoimmune mechanisms, such as some psychotic disorders and drug-resistant epilepsies. (AU)


Assuntos
Humanos , Autoanticorpos/metabolismo , Doenças Autoimunes/patologia , Síndromes Paraneoplásicas do Sistema Nervoso/patologia , Encefalite Límbica/patologia , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/etiologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/etiologia , Doenças Autoimunes/terapia , Literatura de Revisão como Assunto , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Síndromes Paraneoplásicas do Sistema Nervoso/etiologia , Síndromes Paraneoplásicas do Sistema Nervoso/terapia , Encefalite Límbica/diagnóstico , Encefalite Límbica/etiologia , Encefalite Límbica/história , Encefalite Límbica/terapia , Epilepsia/diagnóstico , Epilepsia/etiologia
18.
Med Sci (Paris) ; 36(10): 893-899, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-33026332

RESUMO

Non-infectious uveitis is a heterogenous group of potentially blinding ocular autoimmune diseases that may represent a manifestation of a systemic condition or may affect the eyes only. A systemically administered anti-TNF has recently been approved for the treatment of non-infectious uveitis, broadening the therapeutic arsenal available to control intraocular inflammation and reduce uveitis complications that can lead to vision loss. When uveitis affects only the eyes, a local anti-TNF-α administration strategy could optimize the ocular therapeutic effect and reduce undesirable systemic side-effects. A new ocular method of non-viral gene therapy, currently in development, may broaden the indications for ocular anti-TNF-α agents, not only for uveitis but also for other diseases in which TNF-α-mediated neuro-inflammation has been demonstrated.


Assuntos
Terapia Genética , Fator de Necrose Tumoral alfa/imunologia , Uveíte/terapia , Transtornos da Visão/prevenção & controle , Anticorpos Neutralizantes/genética , Anticorpos Neutralizantes/uso terapêutico , Doenças Autoimunes/terapia , Terapia Genética/métodos , Terapia Genética/tendências , Humanos , Fator de Necrose Tumoral alfa/antagonistas & inibidores
19.
N Engl J Med ; 383(17): 1635-1644, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-32897035

RESUMO

BACKGROUND: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by progressive surfactant accumulation and hypoxemia. It is caused by disruption of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, which pulmonary alveolar macrophages require to clear surfactant. Recently, inhaled GM-CSF was shown to improve the partial pressure of arterial oxygen in patients with aPAP. METHODS: In a double-blind, placebo-controlled, three-group trial, we randomly assigned patients with aPAP to receive the recombinant GM-CSF molgramostim (300 µg once daily by inhalation), either continuously or intermittently (every other week), or matching placebo. The 24-week intervention period was followed by an open-label treatment-extension period. The primary end point was the change from baseline in the alveolar-arterial difference in oxygen concentration (A-aDo2) at week 24. RESULTS: In total, 138 patients underwent randomization; 46 were assigned to receive continuous molgramostim, 45 to receive intermittent molgramostim, and 47 to receive placebo. Invalid A-aDo2 data for 4 patients (1 in each molgramostim group and 2 in the placebo group) who received nasal oxygen therapy during arterial blood gas measurement were replaced by means of imputation. For the primary end point - the change from baseline in the A-aDo2 at week 24 - improvement was greater among patients receiving continuous molgramostim than among those receiving placebo (-12.8 mm Hg vs. -6.6 mm Hg; estimated treatment difference, -6.2 mm Hg; P = 0.03 by comparison of least-squares means). Patients receiving continuous molgramostim also had greater improvement than those receiving placebo for secondary end points, including the change from baseline in the St. George's Respiratory Questionnaire total score at week 24 (-12.4 points vs. -5.1 points; estimated treatment difference, -7.4 points; P = 0.01 by comparison of least-squares means). For multiple end points, improvement was greater with continuous molgramostim than with intermittent molgramostim. The percentages of patients with adverse events and serious adverse events were similar in the three groups, except for the percentage of patients with chest pain, which was higher in the continuous-molgramostim group. CONCLUSIONS: In patients with aPAP, daily administration of inhaled molgramostim resulted in greater improvements in pulmonary gas transfer and functional health status than placebo, with similar rates of adverse events. (Funded by Savara Pharmaceuticals; IMPALA ClinicalTrials.gov number, NCT02702180.).


Assuntos
Doenças Autoimunes/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Proteinose Alveolar Pulmonar/tratamento farmacológico , Administração por Inalação , Adulto , Doenças Autoimunes/fisiopatologia , Doenças Autoimunes/terapia , Lavagem Broncoalveolar , Método Duplo-Cego , Esquema de Medicação , Tolerância ao Exercício , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Proteinose Alveolar Pulmonar/fisiopatologia , Proteinose Alveolar Pulmonar/terapia , Troca Gasosa Pulmonar , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Teste de Caminhada
20.
Scand J Immunol ; 92(5): e12961, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32853446

RESUMO

The new era of immune and reconstitution therapy of autoimmune disorders is ongoing. However, endocrine autoimmune diseases comprise a group of elaborating pathologies where the development of new treatment strategies remains slow. Substitution of the missing hormones is still standard practice, taking care of the devastating symptoms but not the cause of disease. As our knowledge of the genetic contribution to the aetiology of endocrine disorders increases and early diagnostic tools are available, it is now possible to identify persons at risk before they acquire full-blown disease. This review summarizes current knowledge and treatment of endocrine autoimmune disorders, focusing on type 1 diabetes, Addison's disease, autoimmune thyroid diseases and primary ovarian insufficiency. We explore which new therapies might be used in the different stages of the disease, focus on legalized therapy and elaborate on the ongoing clinical studies for these diseases and the research front, before hypothesizing on the way ahead.


Assuntos
Doença de Addison/imunologia , Doenças Autoimunes/imunologia , Diabetes Mellitus Tipo 1/imunologia , Doenças do Sistema Endócrino/imunologia , Insuficiência Ovariana Primária/imunologia , Doenças da Glândula Tireoide/imunologia , Doença de Addison/genética , Doença de Addison/terapia , Doenças Autoimunes/genética , Doenças Autoimunes/terapia , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/terapia , Doenças do Sistema Endócrino/genética , Doenças do Sistema Endócrino/terapia , Feminino , Humanos , Imunoterapia/métodos , Modelos Imunológicos , Insuficiência Ovariana Primária/genética , Insuficiência Ovariana Primária/terapia , Doenças da Glândula Tireoide/genética , Doenças da Glândula Tireoide/terapia
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