الملخص
Fundamento: Fatores de risco definidos para HIV e tradicionais podem estar associados a um aumento de eventos cardiovasculares. Estudos recentes sugerem que a resposta imune humoral à LDL modificada pode estar associada ao processo de aterosclerose. Objetivos: Avaliar a presença de anti-LDL oxidada e de peptídeos derivados da Apolipoproteína B no sangue, bem como sua associação à função endotelial na infecção por HIV. Métodos: Este estudo incluiu consecutivamente sujeitos com idade, sexo e dados demográficos correspondentes em dois grupos: (1) indivíduos infectados com HIV e naïve para terapia antiviral e (2) indivíduos não infectados. A aterosclerose subclínica foi avaliada pela espessura íntima-média, utilizando-se a ultrassonografia das artérias carótidas. A função endotelial foi determinada pela dilatação mediada por fluxo (DMF) da artéria braquial por ultrassonografia. Os níveis de autoanticorpos (IgM, IgG) de lipoproteínas de baixa densidade antioxidadas (LDL-ox), fragmentos de peptídeos antiapolipoproteína B (peptídeos ApoB-D e 0033G-Cys), e citocina foram avaliados por meio de ELISA. Resultados: Os resultados deste estudo não mostraram diferenças na aterosclerose subclínica entre os grupos. Entretanto, os sujeitos infectados com HIV apresentaram uma DMF mais baixa, em comparação com os sujeitos não infectados. Portanto, os sujeitos infectados com HIV apresentaram níveis mais altos de citocinas inflamatórias, títulos de IgG anti-LDL-ox, e IgG anti-ApoB-D. Em contraste, títulos de IgM anti-ApoB-D foram mais baixos em indivíduos infectados com HIV e associados a funções endoteliais diminuídas. Conclusões: Os resultados deste estudo mostram que a infecção por HIV, em sujeitos naïve, está associada à disfunção endotelial e à diminuição de anticorpos naturais para antígenos Apo-B.
Abstract Backgorund: Traditional and HIV-defined risk factors may be associated with an increase in cardiovascular events. Recent studies have suggested that the humoral immune response to modified LDL may be associated with the process of atherosclerosis. Objectives: To evaluate the presence of anti-oxLDL and apolipoprotein B-derived peptides in the blood, and their association with the endothelial function in HIV-infection. Methods: This study consecutively included subjects matched for age, gender, and demographic data in two groups: (1) HIV-infected and naïve for antiviral therapy and (2) uninfected individuals. Subclinical atherosclerosis was assessed by intimal-media thickness, using ultrasonography of the carotid arteries. Endothelial function was determined by flow-mediated dilatation (FMD) of the brachial artery by ultrasonography. Autoantibodies (IgM, IgG) anti-oxidized low-density lipoprotein (oxLDL), anti-apolipoprotein B-peptide fragments (ApoB-D and 0033G-Cys peptides), and cytokine levels were evaluated by ELISA. Results: This study's results showed no difference in subclinical atherosclerosis between groups; however, HIV-infected subjects showed a lower FMD, when compared to non-infected subjects. Therefore, HIV-infected subjects showed higher levels of inflammatory cytokines, titers of IgG anti-oxLDL, and IgG anti-ApoB-D. In contrast, titers of IgM anti-ApoB-D were lower in HIV-infected individuals and associated with reduced endothelial functions. Conclusions: This study's results show that HIV infection, in naïve subjects, is associated with endothelial dysfunction and a decline of natural antibodies to apo-B antigens.
الموضوعات
Humans , Autoantigens , HIV Infections , Apolipoproteins B , Immunoglobulin G , Immunoglobulin M , Lipoproteins, LDLالملخص
OBJECTIVE@#To explore the genetic basis for a pedigree affected with Alport syndrome.@*METHODS@#Next generation sequencing and Sanger sequencing was applied to detect potential variants of the COL4A3, COL4A4 and COL4A5 genes among members from the pedigree and 100 unrelated healthy controls.@*RESULTS@#The proband and his twin brother were found to carry two novel variants, namely c.4953G>A and c.4623C>A, of the COL4A4 gene, which were respectively inherited from her father and mother. The same variants were not detected among the 100 healthy controls and medical literature. Based on the guidelines of the American College of Medical Genetics and Genomics, both the c.4953G>A and c.4623C>A variants were predicted to be pathogenic (PVS1+PM2_supporting+PP1).@*CONCLUSION@#The c.4953G>A and c.4623C>A variants of the COLA4A gene probably underlay the Alport syndrome in this pedigree. Above finding has enriched the spectrum of COLA4A gene variants.
الموضوعات
Child , Female , Humans , Male , Autoantigens/genetics , Collagen Type IV/genetics , Mutation , Nephritis, Hereditary/genetics , Pedigreeالملخص
OBJECTIVE@#To construct a PA28γ overexpression cell line and determine its effects after infecting an oral squa-mous cell carcinoma (OSCC) cell line.@*METHODS@#The PA28γ gene was cloned into the pLOV.CMV.cherry.2A.EF1a.PuroR lentiviral vector by polymerase chain reaction (PCR), and PCR and DNA sequencing alignment analysis were used for identification. Then, 293T cells were used to package viral diseases. Infected OSCC cells were used to construct a cell line with stable PA28γ overexpression. Finally, the level of PA28γ expression in the OSCC cell line was detected through Western blot.@*RESULTS@#The successful construction of PA28γ recombinant lentiviral vectors was confirmed by DNA sequencing. The results of immunofluorescence showed that the PA28γ overexpression lentivirus successfully infected the OSCC cells and showed cherry red fluorescence. The results of Western blot demonstrated that the constructed cells with stable PA28γ overexpression significantly increased the expression of PA28γ.@*CONCLUSIONS@#The PA28γ overexpression lentiviral vector can significantly increase its protein expression in OSCC cells. We provide a stable OSCC cell line for further study on the effect of PA28γ in OSCC.
الموضوعات
Humans , Autoantigens , Carcinoma, Squamous Cell , Cell Line, Tumor , Genetic Vectors , Lentivirus , Mouth Neoplasms , Proteasome Endopeptidase Complex , Transfectionالملخص
Resumen El lupus eritematoso generalizado (LEG) es una enfermedad autoinmune crónica caracterizada por la pérdida de la tolerancia a los antígenos propios y la síntesis de diferentes autoanticuerpos con la formación y depósito de complejos inmunes y el daño de múltiples órganos. Las células T reguladoras (Treg) desempeñan un papel esencial en el mantenimiento de la tolerancia periférica, controlan el estado de activación del sistema inmune y limitan las respuestas autoinmunes. El estudio del número y la función de las diferentes subpoblaciones de células Treg en LEG ha sido objeto de una intensa investigación. Dependiendo del fenotipo de las células Treg analizado se ha reportado que la frecuencia de estas células en pacientes con LEG se encuentra disminuida, aumentada o sin alteraciones. Además, diferentes grupos han descrito que la función supresora de las células Treg de los pacientes con LEG se encuentra reducida o no se ve afectada. En conjunto, lo datos reportados sugieren que las células Treg desempeñan un papel relevante en la patogénesis del LEG y que estos linfocitos pueden ser considerados blancos potenciales para el diseño de nuevas estrategias terapéuticas para esta enfermedad.
Abstract Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a loss of tolerance to self-antigens and synthesis of different autoantibodies, with the formation and deposition of immune complexes and damage to multiple organs. T regulatory cells (Tregs) play a crucial role in maintaining peripheral tolerance, controlling the state of activation of the immune system and limiting autoimmune responses. The study of the number and function of the different Treg cell subpopulations in SLE has been the subject of intense research. Depending on the analyzed Treg cell phenotype, the frequency of these cells has been reported to be reduced, increased or unaltered in patients with SLE. In addition, different groups have described that Treg cells suppressive function is reduced or unaffected in patients with SLE. Taken together, the reported data suggest that Treg cells play a relevant role in the pathogenesis of SLE and that these lymphocytes can be considered potential targets for the design of new therapeutic strategies for this condition.
الموضوعات
Humans , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Regulatory/immunology , Lupus Erythematosus, Systemic/immunology , Autoantibodies/immunology , Autoantigens/immunology , Lupus Erythematosus, Systemic/physiopathologyالملخص
Laryngeal squamous cell carcinoma (LSCC) is the most common type of head and neck squamous cell carcinoma (HNSCC) worldwide. Protein phosphatase 2A (PP2A) dysfunction has been widely reported in a broad range of malignancies due to its distinctive role in miscellaneous cellular processes. However, it is poorly understood whether aberrant alterations of PP2A are involved in the network of oncogenic events in LSCC. Here, we detected a panel of PP2A-associated proteins using western blot in both laryngeal squamous cell carcinoma tissues and paired adjacent normal tissues from patients (Data S1). We found that phospho-PP2A/C (Y307), α4, cancerous inhibitor of protein phosphatase 2A (CIP2A), Akt, ezrin, phospho-ezrin (T567), 14-3-3, and focal adhesion kinase (FAK) showed increased expression levels in carcinoma tissues relative to normal tissues, while phospho-Akt (T308) showed decreased levels. Our study, thus, provides a rationale for targeting PP2A to develop novel therapies and proposes a combination of interrelated biomarkers for the diagnostic evaluation and prognosis prediction in LSCC.
الموضوعات
Humans , Autoantigens/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/metabolism , Case-Control Studies , Cytoskeletal Proteins/metabolism , Focal Adhesion Kinase 1/metabolism , Gene Expression Profiling , Gene Expression Regulation , Gene Expression Regulation, Neoplastic , Intracellular Signaling Peptides and Proteins/metabolism , Laryngeal Neoplasms/metabolism , Larynx/metabolism , Membrane Proteins/metabolism , Phosphorylation , Protein Phosphatase 2/metabolismالملخص
YKL-40, a secreted glycoprotein, may serve as an autoantigen, which mediates multiple inflammatory diseases and cancers. A high YKL-40 serum level is correlated with metastasis and poor survival in a variety of human cancers. However, the role of YKL-40 in dogs is still under evaluation. Herein, we examined the associations between plasma YKL-40 level and YKL-40 autoantibody (YAA) titers with malignancy and prognosis in canine cancer. Plasma levels of YKL-40 in healthy dogs (n = 20) and in dogs (n = 82) with cancer were evaluated using enzyme-linked immunosorbent assay. Our results indicated that plasma YKL-40 levels were significantly higher (p 180 pg/mL) than in the low YKL-40 group (< 180 pg/mL). The results imply that plasma YKL-40 levels might have the potential to be developed as a marker of malignancy progression and prognosis in canine cancers.
الموضوعات
Animals , Dogs , Humans , Autoantibodies , Autoantigens , Enzyme-Linked Immunosorbent Assay , Glycoproteins , Neoplasm Metastasis , Plasma , Prognosis , Recurrenceالملخص
Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease characterized by production of autoantibodies to various nuclear antigens and overexpression of genes regulated by IFN-I called IFN signature. Genetic studies on SLE patients and mutational analyses of mouse models demonstrate crucial roles of nucleic acid (NA) sensors in development of SLE. Although NA sensors are involved in induction of anti-microbial immune responses by recognizing microbial NAs, recognition of self NAs by NA sensors induces production of autoantibodies to NAs in B cells and production of IFN-I in plasmacytoid dendritic cells. Among various NA sensors, the endosomal RNA sensor TLR7 plays an essential role in development of SLE at least in mouse models. CD72 is an inhibitory B cell co-receptor containing an immunoreceptor tyrosine-based inhibition motif (ITIM) in the cytoplasmic region and a C-type lectin like-domain (CTLD) in the extracellular region. CD72 is known to regulate development of SLE because CD72 polymorphisms associate with SLE in both human and mice and CD72−/− mice develop relatively severe lupus-like disease. CD72 specifically recognizes the RNA-containing endogenous TLR7 ligand Sm/RNP by its extracellular CTLD, and inhibits B cell responses to Sm/RNP by ITIM-mediated signal inhibition. These findings indicate that CD72 inhibits development of SLE by suppressing TLR7-dependent B cell response to self NAs. CD72 is thus involved in discrimination of self-NAs from microbial NAs by specifically suppressing autoimmune responses to self-NAs.
الموضوعات
Animals , Humans , Mice , Antigens, Nuclear , Autoantibodies , Autoantigens , Autoimmune Diseases , Autoimmunity , B-Lymphocytes , Cytoplasm , Dendritic Cells , Discrimination, Psychological , Immunoreceptor Tyrosine-Based Inhibition Motif , Lectins, C-Type , Lupus Erythematosus, Systemic , RNAالملخص
ABSTRACT Objectives: American Thyroid Association (ATA)'s new guidelines recommend use of population-based trimester-specific reference range (RR) for thyrotropin (TSH) in pregnancy. The aim of this study was to determine first trimester TSH RR for a population of pregnant women in Rio de Janeiro State. Subjects and methods: Two hundred and seventy pregnant women without thyroid illness, defined by National Academy of Clinical Biochemistry, and normal iodine status were included in this sectional study. This reference group (RG) had normal median urinary iodine concentration (UIC = 219 μg/L) and negative anti-thyroperoxidase antibodies (TPOAb). Twin pregnancy, trophoblastic disease and use of drugs or supplements that influence thyroid function were excluded. In a second step, we defined a more selective reference group (SRG, n = 170) by excluding patients with thyroiditis pattern on thyroid ultrasound and positive anti-thyroglobulin antibodies. This group also had normal median UIC. At a final step, a more selective reference group (MSRG, n = 130) was defined by excluding any pregnant women with UIC < 150 μg/L. Results: In the RG, median, 2.5th and 97.5th percentiles of TSH were 1.3, 0.1, and 4.4 mIU/L, respectively. The mean age was 270 ± 5.0 and the mean body mass index was 25.6 ± 5.2 kg/m2. In the SRG and MSRG, 2.5th and 975th percentiles were 0.06 and 4.0 (SRG) and 0.1 and 3.6 mIU/L (MSRG), respectively. Conclusions: In the population studied,TSH upper limit in the first trimester of pregnancy was above 2.5 mIU/L. The value of 3.6 mIU/L, found when iodine deficiency and thyroiditis (defined by antibodies and ultrasound characteristics) were excluded, matches recent ATA guidelines.
الموضوعات
Humans , Female , Pregnancy , Adult , Young Adult , Pregnancy Trimester, First/blood , Thyroid Gland/diagnostic imaging , Thyrotropin/blood , Practice Guidelines as Topic/standards , Reference Values , Autoantibodies/blood , Autoantigens/blood , Thyroid Function Tests/standards , Brazil , Thyrotropin/standards , Cross-Sectional Studies , Ultrasonography , Iron-Binding Proteins/blood , Iodide Peroxidase/urine , Iodide Peroxidase/bloodالملخص
A alopecia areata é afecção crônica dos folículos pilosos e das unhas, de etiologia desconhecida, que determina queda dos cabelos e/ou pelos. Apresenta-se sob diversas formas clínicas, sendo atípica a forma difusa, em que há perda aguda e difusa de cabelos. Aceita-se que exista uma base autoimune órgão-específica mediada por células T na alopecia areata, e estudos apontam que o autoantígeno é associado ao melanócito. Relatamos o caso de paciente que apresentou a forma difusa com preservação dos fios em canície.
Alopecia areata is a chronic condition of hair follicles and nails with unknown etiology, which causes hair loss. It emerges in several clinical types, with the diffuse form, where there is acute and diffuse hair loss, being atypical. It is generally accepted that there is a T-cell mediated, organ-specific autoimmune base in alopecia areata and studies indicate that the autoantigen is associated with melanocytes. The authors of the present paper report the case of a patient who had the diffuse form of alopecia areata, with preservation of the gray hair strands
الموضوعات
Hair , Autoantigens , Alopecia , Alopecia Areata , Melanocytesالملخص
Introducción: las fisuras anales son un problema de salud importante en la población cubana, incluso con la supresión de los factores desencadenantes, muchas de ellas tienden a la cronicidad; su evolución es tórpida, y es elevado el riesgo de complicación de las mismas. Objetivo: evaluar la cicatrización de las fisuras anales mediante lisado plaquetario en el Hospital General Docente Comandante Pinares de San Cristóbal. Método: se realizó un estudio cuasi experimental en el servicio de cirugía general del Hospital General Docente Comandante Pinares desde enero 2015 hasta junio 2017. Se incluyeron en el estudio todos los pacientes adultos, de ambos sexos, atendidos por el diagnóstico de fisura anal con inadecuada respuesta al tratamiento convencional y sin otras enfermedades de base que impidieran el uso de la terapia regenerativa. A todos los pacientes se les solicitó el consentimiento informado previa explicación de las características del estudio. Resultados: la hemorroidectomía fue el proceder más frecuente asociado a las fisuras anales. El dolor fue el síntoma predominante antes del tratamiento. La reducción del área de la fisura fue evidente en los tratados con lisado. El efecto final en los pacientes tratados con el método fue positivo. Conclusiones: se comprobó que el lisado plaquetario usado para la cicatrización de la fisura anal crónica fue efectivo con un resultado de satisfacción por parte de los pacientes, con un mínimo de reacciones adversas. Puede representar un futuro promisorio en el tratamiento de esta enfermedad(AU)
Introduction: Anal fissures are an important health problem in the Cuban population, even with the suppression of the triggering factors, many of them tend to chronicity; its evolution is torpid, and their risk for complication is high. Objective: To evaluate the healing of anal fissures by platelet lysate in Comandante Pinares General Teaching Hospital in San Cristóbal. Method: A quasi-experimental study was performed in the general surgery service of Comandante Pinares General Teaching Hospital, from January 2015 to June 2017. All adult patients, of both sexes, were attended upon diagnosis of anal fissure and were included in the study. with inadequate response to conventional treatment and without other underlying diseases that could prevent the use of regenerative therapy. All patients were asked for their informed consent prior explanation of the study characteristics. Results: Hemorrhoidectomy was the most frequent procedure associated with anal fissures. Pain was the predominant symptom before treatment. The reduction in the area of ââthe fissure was evident in those patients treated with the lysate. The final effect in patients treated with the method was positive. Conclusions: The usage of the platelet lysate for the healing of chronic anal fissure proved effective, with a result of patient satisfaction, with a minimum of adverse reactions. It may represent a promising future in the treatment of this disease(AU)
الموضوعات
Humans , Male , Female , Autoantigens/therapeutic use , Precipitating Factors , Regenerative Medicine/methods , Fissure in Ano/diagnosis , Data Collection/statistics & numerical dataالملخص
Background: Autologous whole blood (AWB) administration is described as alternative/complementary medical practice widely employed in medical and veterinary therapy against infections, chronic pathologies and neoplasias. Our aim is to investigate in vivo biological effect of AWB using healthy murine models under the course of Trypanosoma cruzi acute infection. Methods: The first set of studies consisted of injecting different volumes of AWB and saline (SAL) into the posterior region of quadriceps muscle of healthy male Swiss mice under distinct therapeutic schemes evaluating: animal behavior, body and organ weight, hemogram, plasmatic biochemical markers for tissue damage and inflammatory cytokine levels and profile. To assess the impact on the experimental T. cruzi infection, different schemes (prior and post infection) and periods of AWB administration (from one up to 10 days) were conducted, also employing heterologous whole blood (HWB) and evaluating plasma cytokine profile. Results: No major adverse events were observed in healthy AWB-treated mice, except gait impairment in animals that received three doses of 20 L AWB in the same hind limb. AWB and SAL triggered an immediate polymorphonuclear response followed by mononuclear infiltrate. Although SAL triggered an inflammatory response, the kinetics and intensity of the histological profile and humoral mediator levels were different from AWB, the latter occurring earlier and more intensely with concomitant elevation of plasma IL-6. Inflammatory peak response of SAL, mainly composed of mononuclear cells with IL-10, was increased at 24 h. According to the mouse model of acute T. cruzi infection, only minor decreases ( 30%) in the parasitemia levels were produced by AWB and HWB given before and after infection, without protecting against mortality. Rises in IFN-gamma, TNF-alpha and...
الموضوعات
Animals , Mice , Autoantigens/therapeutic use , Blood Transfusion, Autologous , Trypanosoma cruziالملخص
Nefropatia membranosa idiopática é uma causa de síndrome nefrótica cuja etiopatogenia não está completamente esclarecida. Trata-se de uma doença imunologicamente mediada, na qual a deposição de imunocomplexos decorre da reação antígenoanticorpo in situ, na região subepitelial glomerular. A maioria dos antígenos envolvidos identificados são alvos da IgG4, subclasse predominante em imunofluorescências renais na nefropatia membranosa idiopática, em contraste com as formas secundárias da doença, nas quais IgG1, IgG2 e IgG3 prevalecem. Apesar da IgG4 ser um subtipo de imunoglobulina com baixa capacidade de ativação do complemento, há várias evidências deste envolvimento na glomerulopatia (GMP). Esses dados, em conjunto com achados de depósitos glomerulares de lectina ligadora de manose, um dos principais componentes da via das lectinas do complemento, podem sugerir que tanto a via da lectina como a IgG4 estão envolvidas nesta patologia. Os motivos que desencadeiam a formação dos imunocomplexos e a ativação das vias do complemento nesta doença são incertos. A hipótese mais aceita é a de que a nefropatia membranosa idiopática resulte do conjunto de três condições: presença de proteínas com conformações alteradas que passam a atuar como autoantígenos, anticorpos do tipo IgG4 contra estes antígenos, e susceptibilidade genética. O objetivo foi verificar o possível papel da IgG4 na etiopatogenia da nefropatia membranosa primária segundo o que foi publicado até o momento na base de dados MEDLINE/PubMed, a partir de uma revisão narrativa.
Idiopathic membranous nephropathy is a frequent cause of nephrotic syndrome and its etiopathogenesis is not fully elucidated. In this immune mediated disease, the deposition of immune complexes is the result of an antigen-antibody reaction in situ, in the glomerular subepithelial region. Most of the antigens involved and so far identified are targets of IgG4, a predominant IgG subclass in renal immunofluorescence analysis of idiopathic membranous nephropathy, in contrast with secondary forms of the disease, in which IgG1, IgG2 and IgG3 are prevalent. Even though IgG4 is an immunoglobulin subclass with low complement activation capacity, there is abundant evidence of its involvement in the glomerulopathy. These data, together with findings of glomerular deposition of mannose-binding lectin a major component of the lectin pathway in the complement system may suggest that both the lectin pathway and IgG4 are involved in this pathology. The reasons behind the formation of immune complexes and the activation of complement pathways in this disease are unknown. The most widely accepted hypothesis is that idiopathic membranous nephropathy stems from a combination of three conditions: presence of proteins with altered conformations, which start to act as autoantigens; IgG4 antibodies against these antigens; and genetic susceptibility. The objective of this narrative review was to analyze the possible role of IgG4 in the etiopathogenesis of primary idiopathic membranous nephropathy based on articles published to date in the MEDLINE/PubMed database.
الموضوعات
Humans , Male , Female , Immunoglobulin G , Glomerulonephritis, Membranous , Complement Activation , Autoantigens , Review Literature as Topic , Antigen-Antibody Complexالملخص
The clearance of apoptotic cells is an essential process for tissue homeostasis. To this end, cells undergoing apoptosis must display engulfment signals, such as ‘find-me' and ‘eat-me' signals. Engulfment signals are recognized by multiple types of phagocytic machinery in phagocytes, leading to prompt clearance of apoptotic cells. In addition, apoptotic cells and phagocytes release tolerogenic signals to reduce immune responses against apoptotic cell-derived self-antigens. Here we discuss recent advances in our knowledge of engulfment signals, the phagocytic machinery and the signal transduction pathways for apoptotic cell engulfment.
الموضوعات
Apoptosis , Autoantigens , Homeostasis , Phagocytes , Signal Transductionالملخص
MicroRNAs (miRNAs) recruit the RNA-induced silencing complex (RISC) to repress the translation of target mRNAs. While the 5' 7-methylguanosine cap of target mRNAs has been well known to be important for miRNA repression, the underlying mechanism is not clear. Here we show that TNRC6A interacts with eIF4E2, a homologue of eIF4E that can bind to the cap but cannot interact with eIF4G to initiate translation, to inhibit the translation of target mRNAs. Downregulation of eIF4E2 relieved miRNA repression of reporter expression. Moreover, eIF4E2 downregulation increased the protein levels of endogenous IMP1, PTEN and PDCD4, whose expression are repressed by endogenous miRNAs. We further provide evidence showing that miRNA enhances eIF4E2 association with the target mRNA. We propose that miRNAs recruit eIF4E2 to compete with eIF4E to repress mRNA translation.
الموضوعات
Humans , Autoantigens , Metabolism , Cell Line , Eukaryotic Initiation Factor-4E , Metabolism , Gene Silencing , MicroRNAs , Genetics , Protein Transport , RNA, Messenger , Genetics , RNA-Binding Proteins , Metabolismالملخص
Abstract: Bullous pemphigoid is a blistering autoimmune disease characterized by two hemidesmosomal proteins (anti-BP180 and 230). Pemphigus, by contrast, is characterized by two autoantibodies (anti-desmoglein 1 and 3). Coexistence of autoantibodies of bullous pemphigoid and pemphigus in a patient is rare. A 25-year-old male patient was admitted to our hospital, reporting a 3-month history of multiple papules, vesicles, and erosions over an extensive erythema on the entire body. Laboratory tests showed high levels of serum IgE, anti-BP180 antibodies, and anti-desmoglein 1 and 3. Histopathologic and immunopathologic features were characterized by bullous pemphigoid. No improvement was seen with systemic corticosteroid therapy, however, pulse corticosteriod therapy combined with methylprednisolone, immunosuppressants, immunomodulators, and plasmapheresis led to the recovery of his condition with numerous milia.
الموضوعات
Humans , Male , Adult , Immunoglobulin E/blood , Pemphigoid, Bullous/immunology , Pemphigoid, Bullous/pathology , Desmogleins/immunology , Keratosis/immunology , Keratosis/pathology , Skin/pathology , Autoantibodies/blood , Autoantigens/blood , Biopsy , Methylprednisolone/therapeutic use , Pemphigoid, Bullous/drug therapy , Non-Fibrillar Collagens/blood , Pressure Ulcer/pathology , Glucocorticoids/therapeutic use , Keratosis/drug therapyالملخص
Abstract The aim of this study was to determine expression, not previously described, of PLUNC (palate, lung, and nasal epithelium clone) (BPI-fold containing) proteins in major and minor salivary glands from very early fetal tissue to the end of the second trimester and thus gain further insight into the function of these proteins. Early fetal heads, and major and minor salivary glands were collected retrospectively and glands were classified according to morphodifferentiation stage. Expression of BPI-fold containing proteins was localized through immunohistochemistry. BPIFA2, the major BPI-fold containing protein in adult salivary glands, was detected only in the laryngeal pharynx; the lack of staining in salivary glands suggested salivary expression is either very late in development or is only in adult tissues. Early expression of BPIFA1 was seen in the trachea and nasal cavity with salivary gland expression only seen in late morphodifferentiation stages. BPIFB1 was seen in early neural tissue and at later stages in submandibular and sublingual glands. BPIFA1 is significantly expressed in early fetal oral tissue but BPIFB1 has extremely limited expression and the major salivary BPIF protein (BPIFA2) is not produced in fetal development. Further studies, with more sensitive techniques, will confirm the expression pattern and enable a better understanding of embryonic BPIF protein function.
الموضوعات
Humans , Phosphoproteins/analysis , Salivary Glands/chemistry , Salivary Proteins and Peptides/analysis , Autoantigens/analysis , Glycoproteins/analysis , Proteins/analysis , Fetus/chemistry , Palate/embryology , Palate/chemistry , Salivary Glands/embryology , Time Factors , Tongue/embryology , Tongue/chemistry , Immunohistochemistry , Retrospective Studies , Gestational Age , Fetal Development , Epithelium/chemistry , Head/embryology , Neck/embryologyالملخص
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.
الموضوعات
Humans , Autoantigens/genetics , Viral Proteins/genetics , Thyroiditis, Autoimmune/immunology , Sequence Homology, Amino Acid , Hepacivirus/genetics , Polyproteins/genetics , Thyroiditis, Autoimmune/virology , Hepacivirus/immunology , Molecular Mimicry/genetics , Genotyping Techniques , Epitopes/geneticsالملخص
Autoimmune retinopathy (AIR) is an immune-mediated retinopathy, resulting from an immunologic process caused by the aberrant recognition of retinal antigens as autoantigens. The diagnosis of AIR involves the detection of antiretinal antibodies with concurrent clinical and electrophysiological evidence of retinopathy. A 40-year-old patient presented with progressive loss of bilateral vision over several months. A fundus examination was unremarkable. Spectral domain optical coherence tomography revealed a blurred photoreceptor ellipsoid zone at the subfoveal region in both eyes with more prominent disruption in the left eye. Full-field electroretinography (ERG) showed relatively normal rod and cone responses in the right eye, and decreased photopic bwaves with minimal attenuation of a-waves in the left eye. Multifocal ERG demonstrated slightly reduced amplitude of the inner segment ring in the right eye and decreased amplitudes and delayed latencies of all modalities in the left eye. The patient was suspected to have AIR and it was supported by positive Western blots for 23-kDa protein, enolase (46-kDa), aldolase (40-kDa), 62-kDa and 78-kDa proteins and by immunohistochemical staining of human retinal bipolar and ganglion cells. Despite the immunosuppressive treatment, the destruction of the retinal photoreceptors progressed, and immunosuppressive interventions produced very little visual improvement. We report on what is, to the best of our knowledge, the very first case of serologically confirmed nonparaneoplastic AIR in Korea.
الموضوعات
Humans , Autoantibodies/blood , Autoantigens , Autoimmune Diseases/immunology , Electroretinography , Immunologic Factors , Paraneoplastic Syndromes/immunology , Paraneoplastic Syndromes, Ocular , Phosphopyruvate Hydratase , Recoverin , Republic of Korea , Retina/immunology , Retinal Diseases/immunology , Tomography, Optical Coherenceالملخص
PURPOSE: Atherosclerosis is classically defined as an immune-mediated disease characterized by accumulation of low-density lipoprotein cholesterol over intima in medium sized and large arteries. Recent studies have demonstrated that both innate and adaptive immune responses are involved in atherosclerosis. In addition, experimental and human models have recognized many autoantigens in pathophysiology of this disease. Oxidized low-density lipoproteins, beta2 glycoprotein I (beta-2-GPI), and heat shock protein 60 (HSP60) are the best studied of them which can represent promising approach to design worthwhile vaccines for modulation of atherosclerosis. MATERIALS AND METHODS: In silico approaches are the best tools for design and evaluation of the vaccines before initiating the experimental study. In this study, we identified immunogenic epitopes of HSP60, ApoB-100, and beta-2-GPI as major antigens to construct a chimeric protein through bioinformatics tools. Additionally, we have evaluated physico-chemical properties, structures, stability, MHC binding properties, humoral and cellular immune responses, and allergenicity of this chimeric protein by means of bioinformatics tools and servers. RESULTS: Validation results indicated that 89.1% residues locate in favorite or additional allowed region of Ramachandran plot. Also, based on Ramachandran plot analysis this protein could be classified as a stable fusion protein. In addition, the epitopes in the chimeric protein had strong potential to induce both the B-cell and T-cell mediated immune responses. CONCLUSION: Our results supported that this chimeric vaccine could be effectively utilized as a multivalent vaccine for prevention and modulation of atherosclerosis.
الموضوعات
Humans , Apolipoprotein B-100 , Arteries , Atherosclerosis , Autoantigens , B-Lymphocytes , beta 2-Glycoprotein I , Chaperonin 60 , Cholesterol , Computational Biology , Computer Simulation , Epitopes , Immune System , Immunity, Cellular , Lipoproteins , Lipoproteins, LDL , T-Lymphocytes , Vaccinesالملخص
Neutrophils are the major antimicrobial cells of the innate immune system, which are recruited rapidly to the sites of infection and provide the primary defense against pathogens. Recent evidence suggests that neutrophils undergo a distinct cell death mechanism called NETosis, which not only contributes to the host defense, but also leads to severe pathological immune responses in cases of dysregulation. Here, we review the general features of NETosis as well as the generation of autoantigens and damage-associated molecular patterns by NETosis in autoimmune diseases. This review discusses the pathogenic role of NETosis in rheumatoid arthritis and systemic lupus erythematosus, where neutrophils may play a key role in the pathogenesis of these diseases, and suggest the possibility of neutrophil extracellular traps as biomarkers and therapeutic targets for the treatment of autoimmune diseases.