Navegando por Palavras-chave "Autoimmunity"

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    Autoimmunity in Hyper-IgM syndrome
    (Springer, 2008-05-01) Jesus, Adriana A.; Duarte, Alberto J. S.; Oliveira, Joao B.; Hosp Coracao; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
    Introduction Immunodeficiency with hyper-IgM (HIGM) results from genetic defects in the CD40-CD40 ligand (CD40L) pathway or in the enzymes required for immunoglobulin class switch recombination and somatic hypermutation. HIGM can thus be associated with an impairment of both B-cell and T-cell activation.Results and discussions There are seven main subtypes of HIGM and the most frequent is X-linked HIGM, resulting from CD40L mutations. in addition to the susceptibility to recurrent and opportunistic infections, these patients are prone to autoimmune manifestations, especially hemato-logic abnormalities, arthritis, and inflammatory bowel disease. Furthermore, organ-specific autoantibodies are commonly found in HIGM patients.Conclusions the mechanisms by which HIGM associates to autoimmunity are not completely elucidated but a defective development of regulatory T cells, the presence of IgM autoantibodies and an impaired peripheral B-cell tolerance checkpoint have been implicated. This article reviews the main subtypes of HIGM syndrome, the clinical autoinumme manifestations found in these patients, and the possible mechanisms that would explain this association.
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    Avaliação fenotípica das células T reguladoras CD4+CD25+CD127LOW em pacientes com lúpus eritematoso sistêmico
    (Universidade Federal de São Paulo (UNIFESP), 2009-04-29) Mesquita Júnior, Danilo [UNIFESP]; Andrade, Luiz Eduardo Coelho [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that is part of the group of rheumatic autoimmune inflammatory diseases, being characterized by heterogeneous clinical and laboratory manifestations. The exact etiopathogenic mechanism underlying SLE still remains obscure. Previousr observations evaluating CD4+ CD25+ TREG cell function in auto-immune diseases detected alterations on frequency and on phenotypic and functional features in murine and human models that support the significant activity of this cell population on autoimmune pathophysiology. In SLE we can observe the existence of a complex interaction network that characterizes the disease, in which many targets for therapeutic intervention may be considered. The present study has focused on TREG cells, since they may represent putative targets for immunomodulatory therapy in this disease. Published data on frequency and phenotype of TREG cells is controversial due to heterogeneity of phenotypic markers and analytic strategies used. The present project aimed to validate an appropriate strategy to identify and quantify TREG in SLE. The CD4+CD25highCD127 low/- panel was validated as an appropriate strategy for identification of Foxp3+ TREG cells in healthy and in SLE patients. The frequency of TREG cells presented normal frequency in active and inactive SLE. In contrast, the frequency of conventional non-regulatory T cells was increased in patients with active disease. We also evaluated the expression of important phenotypic markers for TREG cells biology, including CTLA-4, GITR, PD-1, OX40, HLA-DR, CD95, CD45RO, CD28 and CD40L in patients with active and inactive disease. In addition we evaluated the relationship between the balance of TREG cells versus conventional non-regulatory T cells expressing these markers by means of deriving the TREG/Tconv rate for each surface marker. In patients with active disease we observe reduced levels of TREG cells expressing CTLA-4 and CD28 molecules, and elevated levels of CD40L+ TREG cells. There was an imbalance in TREG/Tconv for GITR, HLA-DR, OX40, CD40L and CD45RO: samples from active SLE patients depicted a decreased TREG/Tconv ratio for GITR, HLA-DR, OX40 and CD45RO and an increased ratto for CD40L when compared with healthy controls. The knowledge on the role of TREG cells in SLE may bring important contribution in devising therapeutic alternatives for this disease.
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    Different MOG(35-55) concentrations induce distinguishable inflammation through early regulatory response by IL-10 and TGF-beta in mice CNS despite unchanged clinical course
    (Elsevier B.V., 2015-02-01) Dias, Alyria Teixeira; Ribeiro De Castro, Sandra Bertelli; De Souza Alves, Caio Cesar; Mesquita, Felipe Pereira; Visona De Figueiredo, Nathalia Stela; Evangelista, Marcilene Gomes; Marques Nogueira Castanon, Maria Christina; Juliano, Maria Aparecida [UNIFESP]; Ferreira, Ana Paula; Univ Fed Juiz de Fora; Fed Univ Valleys Jequitinhonha & Mucuri; Universidade Federal de São Paulo (UNIFESP)
    Multiple sclerosis (MS) shows distinct clinical courses. Experimental autoimmune encephalomyelitis (EAE), a model to study multiple sclerosis, can be induced by different protocols, which show distinct cytokine and antibody production. the factors involved in this heterogeneity remain unclear. the relevance of MUG concentration in triggering a regulatory response in the chronic model of EAE is imprecise. the aim of this study was investigate if 100 or 300 mu g of MOG(35-55) could induce different EAE profiles. Modifications in the concentration of MUG were able to change the patterns of chemokines, cytokines, percentage of cells, inflammatory infiltrate and the development of a regulatory response. However, these changes were unable to modify the intensity of response, which explains the chronic progression of the disease in both concentrations. the results presented in this study contribute to understanding the intricate mechanisms that trigger EAE and provide insights into the pathogenesis of various forms of MS. (C) 2015 Elsevier Inc. All rights reserved.
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    Doença de addison de etiologia auto-imune
    (Sociedade Brasileira de Endocrinologia e Metabologia, 1998-12-01) Silva, Regina do Carmo [UNIFESP]; Kater, Claudio Elias [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Autoimmune Addison's disease is a rare and potentially, fatal endocrinopathy, that can occur either isolated or as part of the types I and II polyglandular autoimmune syndromes (PAS). Adrenocortical autoantibodies are considered sensitive immunological markers of the destructive autoimmune process, and can identify individuals in the pre-clinical stage of the disease. The steroidogenic enzyme 21-hydroxylase (P450c21) represents the major adrenal autoantigen, although other P450 cytochromes (17a-hydroxylase and side chain cleavage) can also trigger an autoimmune response, mainly in the PAS type I and in Addison's disease with associated premature ovarian failure. The role of P45021 autoantibodies in the pathogenesis of the adrenal failure is not yet well established, and the same happens with the anti-ACTH receptor antibodies.
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    Effects of acute aerobic exercise on leukocyte inflammatory gene expression in systemic lupus erythematosus
    (Centro Federal Educacao Tecnologica Rio Grande Norte, 2016) Perandini, L. A.; Sales-de-Oliveira, Diego; Almeida, D. C. [UNIFESP]; Azevedo, Hatylas; Moreira-Filho, C. A.; Cenedeze, Marco Antonio [UNIFESP]; Benatti, F. B.; Lima, F. R.; Borba, Eduardo; Bonfa, E.; Sa-Pinto, A. L.; Roschel, H.; Camara, N. O.; Gualano, B.
    Systemic lupus erythematosus (SLE) is an autoimmune disease with a persistent systemic inflammation. Exercise-induced inflammatory response in SLE remains to be fully elucidated. The aim of this study was to assess the effects of acute exercise on leukocyte gene expression in active (SLEACTIVE) and inactive SLE (SLEINACTIVE) patients and healthy controls (HC). Methods: All subjects (n = 4 per group) performed a 30-min single bout of acute aerobic exercise (similar to 70% of VO2 peak) on a treadmill, and blood samples were collected for RNA extraction from circulating leukocyte at baseline, at the end of exercise, and after three hours of recovery. The expression of a panel of immune-related genes was evaluated by a quantitative PCR array assay. Moreover, network-based analyses were performed to interpret transcriptional changes occurring after the exercise challenge. Results: In all groups, a single bout of acute exercise led to the down-regulation of the gene expression of innate and adaptive immunity at the end of exercise (e.g., TLR3, IFNG, GATA3, FOXP3, STAT4) with a subsequent up-regulation occurring upon recovery. Exercise regulated the expression of inflammatory genes in the blood leukocytes of the SLE patients and HC, although the SLE groups exhibited fewer modulated genes and less densely connected networks (number of nodes: 29, 40 and 58
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    Gene Expression in B-1 Cells from Lupus-Prone Mice
    (Informa Healthcare, 2014-01-01) Novaes e Brito, Ronni Romulo [UNIFESP]; Xander, Patricia [UNIFESP]; Perez, Elizabeth C. [UNIFESP]; Maricato, Juliana Terzi [UNIFESP]; Laurindo, Maria Fl. [UNIFESP]; De Lorenzo, Beatriz H. P. [UNIFESP]; Pellegrino, Renata [UNIFESP]; Bernardo, Viviane [UNIFESP]; Lopes, Jose Daniel [UNIFESP]; Mariano, Mario [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Ctr Univ Sao Camilo
    New Zealand Black X New Zealand White F1 [(NZB/NZW) F1] mice develop an autoimmune condition with similarities to human systemic lupus erythematosus (SLE). in this study, we demonstrate that B-1 cells, which have previously been reported to be involved in several autoimmune diseases, have altered gene expression in these mice. RNA was extracted from purified B-1 cells of disease-free C57BL/6 mice and lupus-prone (NZB/NZW) F1 mice. Gene expression was analysed using DNA microarray techniques and validated by real time reverse transcriptase polymerase chain reaction (RT-PCR). in (NZB/NZW) F1 mice, some genes had altered expression patterns compared to disease-free controls. Specifically, the upregulation of Ifitm1, Pvrl2 and Ifi202b and downregulation of Trp53bp1 mRNA were observed in (NZB/NZW) F1 mice. These genes are known to be associated with autoimmune diseases. This pattern of gene expression in B-1 cells could understanding of the pathogenesis of SLE. Thus, it is reasonable to hypothesise that the altered gene expression observed in B-1 cells in our experimental model is important for SLE prognosis and therapy, and these implications are discussed herein.
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    Humoral autoimmune response heterogeneity in the spectrum of primary biliary cirrhosis
    (Springer, 2013-06-01) Dellavance, Alessandra [UNIFESP]; Cancado, Eduardo Luiz Rachid; Abrantes-Lemos, Clarice Pires; Harriz, Michelle [UNIFESP]; Marvulle, Valdecir [UNIFESP]; Andrade, Luiz Eduardo Coelho [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Fleury Med & Hlth Labs; Universidade de São Paulo (USP)
    To compare autoantibody features in patients with primary biliary cirrhosis (PBC) and individuals presenting antimitochondria antibodies (AMAs) but no clinical or biochemical evidence of disease.A total of 212 AMA-positive serum samples were classified into four groups: PBC (definite PBC, n = 93); PBC/autoimmune disease (AID; PBC plus other AID, n = 37); biochemically normal (BN) individuals (n = 61); and BN/AID (BN plus other AID, n = 21). Samples were tested by indirect immunofluorescence (IIF) on rat kidney (IIF-AMA) and ELISA [antibodies to pyruvate dehydrogenase E2-complex (PDC-E2), gp-210, Sp-100, and CENP-A/B]. AMA isotype was determined by IIF-AMA. Affinity of anti-PDC-E2 IgG was determined by 8 M urea-modified ELISA.High-titer IIF-AMA was more frequent in PBC and PBC/AID (57 and 70 %) than in BN and BN/AID samples (23 and 19 %) (p < 0.001). Triple isotype IIF-AMA (IgA/IgM/IgG) was more frequent in PBC and PBC/AID samples (35 and 43 %) than in BN sample (18 %; p = 0.008; p = 0.013, respectively). Anti-PDC-E2 levels were higher in PBC (mean 3.82; 95 % CI 3.36-4.29) and PBC/AID samples (3.89; 3.15-4.63) than in BN (2.43; 1.92-2.94) and BN/AID samples (2.52; 1.54-3.50) (p < 0.001). Anti-PDC-E2 avidity was higher in PBC (mean 64.5 %; 95 % CI 57.5-71.5 %) and PBC/AID samples (66.1 %; 54.4-77.8 %) than in BN samples (39.2 %; 30.9-37.5 %) (p < 0.001). PBC and PBC/AID recognized more cell domains (mitochondria, nuclear envelope, PML/sp-100 bodies, centromere) than BN (p = 0.008) and BN/AID samples (p = 0.002). Three variables were independently associated with established PBC: high-avidity anti-PDC-E2 (OR 4.121; 95 % CI 2.118-8.019); high-titer IIF-AMA (OR 4.890; 2.319-10.314); antibodies to three or more antigenic cell domains (OR 9.414; 1.924-46.060).The autoantibody profile was quantitatively and qualitatively more robust in definite PBC as compared with AMA-positive biochemically normal individuals.
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    Immunologic derangement preceding clinical autoimmunity
    (Sage Publications Ltd, 2014-10-01) Dellavance, A.; Coelho Andrade, L. E. [UNIFESP]; Fleury Med & Hlth Labs; Universidade Federal de São Paulo (UNIFESP)
    Autoantibodies are valuable markers for the recognition of autoimmune diseases. Over the last 25 years, several investigators have consistently shown that autoantibodies precede the clinical onset of cognate diseases by years or decades. This phenomenon, regularly observed in the natural history of autoimmune diseases, indicates that autoimmunity develops through successive stages across a variable period of time until the characteristic manifestations of disease are clinically apparent. Recent evidence indicates that the pre-clinical stages of autoimmune diseases involve a series of immunologic derangements and that this process is dynamic and progressive. During the years preceding clinical disease onset, there is progressive intensification in the humoral autoimmune response, characterized by increases in autoantibody titer, avidity, number of immunoglobulin isotypes, and spread of epitopes and of autoantigens targeted. This scenario is reminiscent of cancer processes that develop slowly by means of progressive stages, and may be interrupted by early detection and therapeutic intervention. Therefore, it might be reasoned that early intervention may be more effective in reverting the less firmly established autoimmune abnormalities at the pre-clinical stage of autoimmunity. With the continuous progress in novel immunologic therapeutic strategies, one can envision the possibility that early intervention at pre-clinical stages may lead to prevention of overt disease development and even cure of the autoimmune disorder.
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    International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies
    (Bmj Publishing Group, 2014-01-01) Agmon-Levin, Nancy; Damoiseaux, Jan; Kallenberg, Cees; Sack, Ulrich; Witte, Torsten; Herold, Manfred; Bossuyt, Xavier; Musset, Lucille; Cervera, Ricard; Plaza-Lopez, Aresio; Dias, Carlos; Sousa, Maria Jose; Radice, Antonella; Eriksson, Catharina; Hultgren, Olof; Viander, Markku; Khamashta, Munther; Regenass, Stephan; Coelho Andrade, Luis Eduardo [UNIFESP]; Wiik, Allan; Tincani, Angela; Ronnelid, Johan; Bloch, Donald B.; Fritzler, Marvin J.; Chan, Edward K. L.; Garcia-De la Torre, I.; Konstantinov, Konstantin N.; Lahita, Robert; Wilson, Merlin; Vainio, Olli; Fabien, Nicole; Sinico, Renato Alberto; Meroni, Pierluigi; Shoenfeld, Yehuda; Chaim Sheba Med Ctr; Tel Aviv Univ; Maastricht Univ; Univ Groningen; Univ Leipzig; Sch Med; Med Univ Innsbruck; Univ Hosp Leuven; Katholieke Univ Leuven; GH Pitie Salpetriere; Hosp Clin Barcelona; Hosp Univ Pueta Hierro Majadahonda; S Joao Hosp; Fernando Fonseca Hosp; Azienda Osped Osped San Carlo Borromeo; Umea Univ; Univ Hosp Orebro; Univ Orebro; Univ Turku; Kings Coll London; DIA Univ Spital; Universidade Federal de São Paulo (UNIFESP); Statens Serum Inst; Spedali Civil Brescia; Univ Brescia; Uppsala Univ; Massachusetts Gen Hosp; Harvard Univ; Univ Calgary; Univ Florida; Hosp Gen Occidente Seguro Social; Univ Guadalajara; Newark Beth Israel Med Ctr UMDNJ; Univ Oulu; NordLab Oulu; CH Lyon Sud; Univ Milan
    Anti-nuclear antibodies (ANA) are fundamental for the diagnosis of autoimmune diseases, and have been determined by indirect immunofluorescence assay (IIFA) for decades. As the demand for ANA testing increased, alternative techniques were developed challenging the classic IIFA. These alternative platforms differ in their antigen profiles, sensitivity and specificity, raising uncertainties regarding standardisation and interpretation of incongruent results. Therefore, an international group of experts has created recommendations for ANA testing by different methods. Two groups of experts participated in this initiative. the European autoimmunity standardization initiative representing 15 European countries and the International Union of Immunologic Societies/World Health Organization/Arthritis Foundation/Centers for Disease Control and Prevention autoantibody standardising committee. A three-step process followed by a Delphi exercise with closed voting was applied. Twenty-five recommendations for determining ANA (1-13), anti-double stranded DNA antibodies (14-18), specific antibodies (19-23) and validation of methods (24-25) were created. Significant differences between experts were observed regarding recommendations 24-25 (p<0.03). Here, we formulated recommendations for the assessment and interpretation of ANA and associated antibodies. Notably, the roles of IIFA as a reference method, and the importance of defining nuclear and cytoplasmic staining, were emphasised, while the need to incorporate alternative automated methods was acknowledged. Various approaches to overcome discrepancies between methods were suggested of which an improved bench-to-bedside communication is of the utmost importance. These recommendations are based on current knowledge and can enable harmonisation of local algorithms for testing and evaluation of ANA and related autoantibodies. Last but not least, new more appropriate terminologies have been suggested.
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    Marcadores genéticos e auto-imunes do diabetes melito tipo 1: da teoria para a prática
    (Sociedade Brasileira de Endocrinologia e Metabologia, 2008-03-01) Silva, Maria Elizabeth Rossi da; Mory, Denise [UNIFESP]; Davini, Elaine; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
    Type 1 A diabetes mellitus (T1AD) results from the autoimmune destruction of the insulin producing pancreatic beta-cells. The largest contribution to genetic susceptibility comes from several genes located in the major histocompatibility complex on chromosome 6p21.3 (IDDM1 locus), accounting for at least 40% of the family aggregation of this disease. The highest-risk human leukocyte antigen HLA genotype for T1AD is DR3-DQA1*0501-DQB1*0201/DR4-DQA1*0301-DQB1*0302, whereas -DR15-DQA1*0102-DQB1*0602 haplotype is associated with dominant protection. Three other T1D loci associated with predisposition are the Variable Number for Tandem Repeats (VNTR) near the insulin gene (IDDM2), which accounts to 10% of genetic susceptibility, the Cytotoxic T-Lymphocyte-associated Antigen (CTLA-4)(IDDM 12) and the Protein Tyrosine Phosphatasis Nonreceptor-type 22 (PTPN22). Many other gene suspected to predispose to autoimmunity have been investigated. T1AD is frequently associated with autoimmune thyroid disease, celiac disase, Addison´s disease and many other autoimmune diseases, characterized by organ-specific autoantibodies and related to the same genetic background. Using these autoantibodies, organ specific autoimmunity may be detected before the development of clinical disease preventing significant morbidity.
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    Reatividade de anticorpos para glicoesfingolipidios em doenças do sistema nervoso, reumáticas, e na infecção pelo HIV
    (Universidade Federal de São Paulo (UNIFESP), 1996) Zeballos, Roberto Sebastian [UNIFESP]
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    Reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells and diminished FOXP3 expression in patients with Common Variable Immunodeficiency: A link to autoimmunity?
    (Elsevier B.V., 2009-08-01) Genre, J.; Errante, P. R.; Kokron, C. M.; Toledo-Barros, M.; Camara, N. O. S. [UNIFESP]; Rizzo, L. V.; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
    Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disease characterized by defective immunoglobulin production and often associated with autoimmunity. We used flow cytometry to analyze CD4(+)CD25(HIGH)FOXP3(+) T regulatory (Treg) cells and ask whether perturbations in their frequency in peripheral blood could underlie the high incidence of autoimmune disorders in CVID patients. in this study, we report for the first time that CVID patients with autoimmune disease have a significantly reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells in their peripheral blood accompanied by a decreased intensity of FOXP3 expression. Notably, although CVID patients in whom autoimmunity was not diagnosed had a reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells, FOXP3 expression levels did not differ from those in healthy controls. in conclusion, these data suggest compromised homeostasis of CD4(+)CD25(HIGH)FOXP3(+) cells in a subset of CVID patients with autoimmunity, and may implicate Treg cells in pathological mechanisms of CVID. (C) 2009 Elsevier Inc. All rights reserved.
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    The role of kinin B-1 and B-2 receptors in the persistent pain induced by experimental autoimmune encephalomyelitis (EAE) in mice: Evidence for the involvement of astrocytes
    (Elsevier B.V., 2013-06-01) Dutra, Rafael C.; Bento, Allisson F.; Leite, Daniela F. P.; Manjavachi, Marianne N.; Marcon, Rodrigo; Bicca, Maira Assuncao; Pesquero, Joao B. [UNIFESP]; Calixto, Joao B.; Universidade Federal de Santa Catarina (UFSC); Universidade Federal de São Paulo (UNIFESP)
    Multiple sclerosis (MS) is a progressive, demyelinating inflammatory disease of the human central nervous system (CNS). While the primary symptoms of MS affect motor function, it is now recognized that chronic pain is a relevant symptom that affects both animals and MS patients. There is evidence that glial cells, such as astrocytes, play an important role in the development and maintenance of chronic pain. Kinins, notably bradykinin (BK) acting through B-1 (B1R) and B-2 (B2R) receptors, play a central role in pain and inflammatory processes. However, it remains unclear whether kinin receptors are involved in neuropathic pain in MS. Here we investigated by genetic and pharmacological approaches the role of kinin receptors in neuropathic pain behaviors induced in the experimental autoimmune encephalomyelitis (EAE) mouse model. Our results showed that gene deletion or antagonism of kinin receptors, especially B1R, significantly inhibited both tactile and thermal hypersensitivity in EAE animals. By contrast, animals with EAE and treated with a B1R selective agonist displayed a significant increase in tactile hypersensitivity. We also observed a marked increase in B1R mRNA and protein level in the mouse spinal cord 14 days after EAE immunization. Blockade of B1R significantly suppressed the levels of mRNAs for IL-17, IFN-gamma, IL-6, CXCL-1/KC, COX-2 and NOS2, as well as glial activation in the spinal cord. of note, the selective B-1 antagonist DALBK consistently prevented IFN-induced up-regulation of TNF-alpha and IL-6 release in astrocyte culture. Finally, both B1R and B2R antagonists significantly inhibited COX-2 and NOS2 expression in primary astrocyte culture. the B1R was co-localized with immunomarker of astrocytes in the spinal cord of EAE-treated animals. the above data constitute convincing experimental evidence indicating that both kinin receptors, especially the B-1 subtype, exert a critical role in the establishment of persistent hypersensitivity observed in the EAE model, an action that seems to involve a central inflammatory process, possibly acting on astrocytes. Thus, B-1 selective antagonists or drugs that reduce kinin release may have the potential to treat neuropathic pain in patients suffering from MS. (C) 2013 Elsevier Inc. All rights reserved.
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    The role of sleep in pemphigus: a review of mechanisms and perspectives
    (Springer, 2017) Pedroni, Matheus Negrao [UNIFESP]; Hirotsu, Camila [UNIFESP]; Porro, Adriana Maria [UNIFESP]; Tufik, Sergio [UNIFESP]; Andersen, Monica Levy [UNIFESP]
    Pemphigus is an autoimmune bullous disease that causes the development of blisters and erosions on the skin and/or mucosa. Its inflammatory process is mediated by cytokines, which interact with sleep in a bidirectional manner. Pain, a frequent symptom due to pemphigus lesions, is well known to impair sleep quality. Depression is also associated with pemphigus and pro-inflammatory cytokines and may impair sleep. Additionally, a common relationship among other dermatological diseases and sleep has increasingly been described. Poor sleep quality is associated with an increased risk for autoimmune diseases, and insomnia is a comorbidity that has recently been associated with pemphigus. Thus, this review will explore the evidence supporting the likely bidirectional relationship between pemphigus and sleep quality and its possible mechanisms involved. This approach covering both pemphigus and sleep will open a research avenue for future studies focusing on the efficacy of the sleep disorders treatment in patients with pemphigus. In the long term, this may provide relevant information to dermatologists regarding new strategies for the management of pemphigus clinical condition, allowing possibly a better quality of life for the patients.
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    The significance of autoantibodies to DFS70/LEDGFp75 in health and disease: integrating basic science with clinical understanding
    (Springer-Verlag Italia Srl, 2016) Ochs, Robert L.; Mahler, Michael; Basu, Anamika; Rios-Colon, Leslimar; Sanchez, Tino W.; Andrade, Luis E. [UNIFESP]; Fritzler, Marvin J.; Casiano, Carlos A.
    Antinuclear autoantibodies (ANAs) displaying the nuclear dense fine speckled immunofluorescence (DFS-IIF) pattern in HEp-2 substrates are commonly observed in clinical laboratory referrals. They target the dense fine speckled autoantigen of 70 kD (DFS70), most commonly known as lens epithelium-derived growth factor p75 (LEDGFp75). Interesting features of these ANAs include their low frequency in patients with systemic autoimmune rheumatic diseases (SARD), elevated prevalence in apparently healthy individuals, IgG isotype, strong trend to occur as the only ANA specificity in serum, and occurrence in moderate to high titers. These autoantibodies have also been detected at varied frequencies in patients with diverse non-SARD inflammatory and malignant conditions such as atopic diseases, asthma, eye diseases, and prostate cancer. These observations have recently stimulated vigorous research on their clinical and biological significance. Some studies have suggested that they are natural, protective antibodies that could serve as biomarkers to exclude a SARD diagnosis. Other studies suggest that they might be pathogenic in certain contexts. The emerging role of DFS70/LEDGFp75 as a stress protein relevant to human acquired immunodeficiency syndrome, cancer, and inflammation also points to the possibility that these autoantibodies could be sensors of cellular stress and inflammation associated with environmental factors. In this comprehensive review, we integrate our current knowledge of the biology of DFS70/LEDGFp75 with the clinical understanding of its autoantibodies in the contexts of health and disease.
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    Vitamin D-3 Induces IDO+ Tolerogenic DCs and Enhances Treg, Reducing the Severity of EAE
    (Wiley-Blackwell, 2013-04-01) Farias, Alessandro S.; Spagnol, Gabriela S.; Bordeaux-Rego, Pedro; Oliveira, Camila O. F.; Fontana, Ana Gabriela M.; Paula, Rosemeire F. O. de; Santos, Mariana P. A.; Pradella, Fernando; Moraes, Adriel S.; Oliveira, Elaine C.; Longhini, Ana Leda F.; Rezende, Alexandre C. S.; Vaisberg, Mauro Walter [UNIFESP]; Santos, Leonilda M. B.; Universidade Estadual de Campinas (UNICAMP); Universidade Federal de São Paulo (UNIFESP)
    Background A growing body of evidence supports the hypothesis that vitamin D is an important environmental factor in the etiology of T-cell-mediated autoimmune diseases such as multiple sclerosis (MS). Aim the purpose of this study was exploring the mechanisms underlying the beneficial effect of vitamin D3 in encephalomyelitis (EAE). Methods We treated monophasic experimental autoimmune EAE, induced in Lewis rat, with vitamin D3 and adoptively transfer tolerogenic bone marrow-derived DCs generated in the presence of vitamin D3. Results This study provides evidence that the in vivo administration of vitamin D3, as well as the adoptive transfer of vitamin D3-induced IDO+ immature/tolerogenic dendritic cells, leads to a significant increase in the percentage of CD4+CD25+Foxp3+ regulatory T cells in the lymph nodes in a rat model of MS, experimental autoimmune EAE. Concomitant with the increase in this cell population, there is a significant decrease in the number of autoreactive T cells in the central nervous system. Bone marrow-derived DCs cultivated in the presence of vitamin D3 present a tolerogenic profile with high IL-10, TNF, and IDO expression and decreased MHC-II and CD80 expression. the adoptive transfer of IDO + DCs induces a significant increase in the percentage of CD4+CD25+Foxp3+ T cells in the lymph nodes, comparable with vitamin D3 treatment. Conclusion These mechanisms contribute actively to the generation of a microenvironment in the lymph nodes that suppresses the activation of encephalitogenic T cells, resulting in the downregulation of the inflammatory response in the central nervous system.