Molecular mimicry between Zika virus and central nervous system inflammatory demyelinating disorders: the role of NS5 Zika virus epitope and PLP autoantigens / Mimetismo molecular entre o vírus Zika e os distúrbios inflamatórios desmielinizantes do sistema nervoso central: o papel do epítopo NS5 do vírus Zika e dos autoantígenos PLP

Abstract Background Evidence indicates a strong link between Zika virus (ZikV) and neurological complications. Acute myelitis, optic neuritis, polyneuropathy, and encephalomyelitis that mimic inflammatory idiopathic demyelination disorders (HDD) after ZikV infection have been reported in Brazil. Objective The present study aims to investigate the possible occurrence of molecular mimicry between ZikV antigens and Multiple Sclerosis (MS) autoantigens, the most frequent HDD of the central nervous system (CNS). Methods A retrospective cohort study with 305 patients admitted due to suspected arbovirus infection in Rio de Janeiro was performed, all subjects were submitted to neurological examination, and a biological sample was collected for serologic and molecular diagnostic. Bioinformatics tools were used to analyze the peptides shared between ZikV antigens and MS autoantigens. Results Of 305 patients, twenty-six were positive for ZikV and 4 presented IDD patterns found in MS cases. Sequence homology comparisons by bioinformatics approach between NS5 ZikV and PLP MS protein revealed a homology of 5/6 consecutive amino acids (CSSVPV/CSAVPV) with 83% identity, deducing a molecular mimicry. Analysis of the 3D structures revealed a similar conformation with alpha helix presentation. Conclusions Molecular mimicry between NS5 Zika virus antigen and PLP MS autoantigens emerge as a possible mechanism for IDD spectrum in genetically susceptible individuals.

Resumo Antecedentes Evidências indicam uma forte ligação entre o vírus Zika (ZikV) e complicações neurológicas. Mielite aguda, neurite óptica, polineuropatia e encefalomielite que mimetizam distúrbios inflamatórios de desmielinização idiopáticos (DDII) após infecção por ZikV têm sido relatadas no Brasil. Obejtivo O presente estudo tem como objetivo investigar a possível ocorrência de mimetismo molecular entre antígenos do ZikV e autoantígenos da Esclerose Múltipla (EM), a DDII mais frequente do sistema nervoso central (SNC). Métodos Foi realizado um estudo de coorte retrospectivo com 305 pacientes internados por suspeita de infecção por arbovirus no Rio de Janeiro, todos os indivíduos foram submetidos a exame neurológico e coleta de amostra biológica para diagnóstico sorológico e molecular. Ferramentas de bioinformática foram usadas para analisar os peptídeos compartilhados entre antígenos do ZikV e autoantígenos da EM. Resultados Dos 305 pacientes, vinte e seis foram positivos para ZikV e 4 apresentaram padrão IDD encontrado em casos de EM. As comparações de homologia de sequência por abordagem de bioinformática entre a proteína NS5 ZikV e PLP EM revelaram uma homologia de 5/6 aminoácidos consecutivos (CSSVPV/CSAVPV) com 83% de identidade, deduzindo um mimetismo molecular. A análise das estruturas 3D revelou uma conformação semelhante com apresentação em alfa-hélice. Conclusões O mimetismo molecular entre o antígeno NS5 do vírus Zika e o autoantígeno PLP da EM surge como um possível mecanismo para o espectro IDD em indivíduos geneticamente suscetíveis.

Research progress on the molecular mechanism of periodontal pathogens promoting the development of cardiovascular diseases / 口腔疾病防治

@#Periodontitis is a multifactorial infectious and inflammatory disease occurring in tooth-supporting tissues. In recent decades, many studies have reported a potential relationship between periodontitis and cardiovascular disease, and periodontal pathogens are an important factor linking periodontitis and cardiovascular disease. In this review, we summarize updated preclinical studies and epidemiological evidence on the association of these two diseases. Moreover, possible mechanisms accounting for such links are introduced, including bacteremia and direct invasion of pathogens, endotoxemia caused by virulence factors of periodontal pathogens leading to systemic inflammation, abnormal lipid metabolism and oxidative stress, which further affect the inflammatory states of the cardiovascular system. The molecular mimicry theory and the intrinsic correlation of apolipoprotein E between periodontitis and cardiovascular disease require further study. Combined with existing studies, it is reasonable to assume that periodontal treatment and oral hygiene can reduce the risk of cardiovascular disease in patients with periodontitis. More studies are needed to focus on the molecular mechanism linking periodontal pathogens and cardiovascular diseases. These studies will provide evidence that periodontal pathogens directly invade the cardiovascular system or indirectly invade host cells as well as isolate and culture bacteria from the tissues of lesions. Studies should also explore how the local inflammatory state, periodontal pathogens and their products directly influence cardiovascular disease-related biomarkers (C-reactive protein, vascular endothelial growth factor, heat shock protein, etc.) and the mechanism. This information may provide a reference for the effective prevention and treatment of periodontitis and cardiovascular disease in the future.

Anemia hemolítica autoinmune: mecanismos de inducción de autoinmunidad e inmunobiología / Autoimmune hemolytic anemia: mechanisms of autoimmunity induction and immunobiology

Introducción: La patogénesis de la anemia hemolítica autoinmune es un proceso complejo en el que muchos elementos tienen una función esencial que repercuten en la gran heterogeneidad clínica de la enfermedad, pero los mecanismos involucrados en su inducción se desconocen en gran medida. Objetivo: Explicar los principales mecanismos propuestos en el inicio y aparición de la anemia hemolítica autoinmune y su contribución a la fisiopatología de la enfermedad. Métodos: Se realizó una revisión de la literatura en los idiomas inglés y español, de artículos publicados en los últimos 10 años sobre mecanismos propuestos en el inicio de la anemia hemolítica autoinmune. Análisis y síntesis de la información: Los mecanismos propuestos en la inducción de la autoinmunidad contra los eritrocitos incluyen el mimetismo molecular entre antígenos endógenos y antígenos exógenos, el procesamiento desregulado de autoantígenos influenciado por factores adquiridos y la disfunción de los linfocitos B y T. Conclusiones: Los mecanismos propuestos en la aparición de la anemia hemolítica autoinmune brindan información valiosa para mejorar la comprensión de los mecanismos moleculares involucrados y subrayan la complejidad de los fenómenos involucrados en la perdida de la tolerancia hacia los eritrocitos autólogos y el delicado equilibrio entre factores genéticos y ambientales(AU)

Introduction: The pathogenesis of autoimmune hemolytic anemia is a complex process in which many elements play an essential role and have an impact on the great clinical heterogeneity of the disease, but the mechanisms involved in its induction are largely unknown. Objective: To explain the main mechanisms proposed in the initiation and occurrence of autoimmune hemolytic anemia and its contribution to the pathophysiology of the disease. Methods: A review of the literature, in English and Spanish languages, of articles published in the last 10 years on proposed mechanisms in the initiation of autoimmune hemolytic anemia was carried out. Analysis and synthesis of information: Proposed mechanisms for the induction of autoimmunity against erythrocytes include molecular mimicry between endogenous and exogenous antigens, deregulated processing of autoantigens influenced by acquired factors, and B and T cells dysfunction. Conclusions: The proposed mechanisms in the occurrence of autoimmune hemolytic anemia provide valuable information to improve the understanding of the mechanisms involved and underline the complexity of the phenomena involved in the loss of tolerance towards autologous erythrocytes and the delicate balance between genetic and environmental factors(AU)

Structural similarity between thyroid peroxidase [Homo sapiens] and SARS-CoV-2 spike glycoprotein ­ An autoimmune thyroiditis triggering mechanism in COVID-19 carriers? / Similaridade estrutural entre a tireoperoxidase humana [Homo sapiens] e a glicoproteína de superfície do SARS-CoV-2 ­ Um mecanismo de desencadeamento da tiroidite autoimune nos portadores da COVID-19?

Introduction: there are reports of autoimmune disease related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) such neurological syndromes and hematological syndromes, and more recently autoimmune thyroid dysfunctions have been described. These reports suggest that SARS-CoV-2 acts as a probable trigger for triggering the autoimmunity process. Aim: to evaluate structural similarity between thyroid peroxidase [Homo sapiens] (TPO) and SARS-CoV-2 spike glycoprotein (COVID-19), and to propose this similarity as a likely trigger for autoimmune thyroiditis. Methodology: using bioinformatics tools, we compare the amino acids (AA) sequences between protein structure of TPO and chain A COVID-19, chain B COVID-19, and chain C COVID-19, accessible in the National Center for Biotechnology Information database, by Basic Local Alignment Search Tool in order to locate the homologous regions between the sequences of AA. Results: the homology sequence between the TPO and COVID-19 ranged from 27.0 % (10 identical residues out of 37 AA in the sequence) to 56.0% (5 identical residues out of 9 AA in the sequence). The similar alignments demonstrated relatively high E values in function of short alignment. Conclusion: data suggest a possible pathological link between TPO and COVID-19. The structural similarity of AA sequences between TPO and COVID-19 may present a molecular mimicry suggesting the possibility of antigen crossover between TPO and COVID-19 that might represent an immunological basis for autoimmune thyroiditis associated with COVID-19.

Introdução: há relatos de doenças autoimunes relacionadas à síndrome respiratória aguda grave por coronavírus 2 (SARS-CoV-2), tais como síndromes neurológicas e hematológicas, e mais recentemente disfunções autoimunes da tireoide foram descritas. Esses relatos sugerem que o SARS-CoV-2 atue como um provável gatilho para desencadear o processo de autoimunidade. Objetivo: avaliar a similaridade estrutural entre a peroxidase tireoidiana [Homo sapiens] (TPO) e a glicoproteína de superfície SARS-CoV-2 (COVID-19) e propor essa similaridade como provável gatilho para o desencadeamento da tireoidite autoimune. Metodologia: utilizando ferramentas de bioinformática, comparamos as sequências de aminoácidos (AA) entre a estrutura da TPO e a estrutura da cadeia A do COVID-19, a cadeia B do COVID-19 e a cadeia C do COVID-19, acessível no banco de dados do National Center for Biotechnology Information, através da Ferramenta Básica de Pesquisa de Alinhamento Local para localizar as regiões homólogas entre as sequências de AA. Resultados: a sequência de homologia entre o TPO e COVID-19 variou de 27,0% (10 resíduos idênticos em 37 AA nas sequências) a 56,0% (5 resíduos idênticos em 9 AA nas sequências). Os alinhamentos semelhantes demonstraram valores E relativamente altos em função do alinhamento curto. Conclusão: os dados sugerem uma possível ligação patológica entre TPO e COVID-19. A similaridade estrutural das sequências de AA entre TPO e COVID-19 pode apresentar um mimetismo molecular sugerindo a possibilidade de cruzamento de antígeno entre TPO e COVID-19 que podem representar uma base imunológica para tireoidite autoimune associada a COVID-19.

The role of pathogen infections in the development and progression of autoimmune liver diseases / 临床肝胆病杂志

The etiology and pathogenesis of autoimmune liver diseases has always been a hot area of research. Pathogen infections can elicit an autoimmune response and often become the key pathogenic factor of immune diseases. Based on the literature data and the author's clinical experience, this review will briefly introduce the role and influence of pathogen infections in the development and progression of autoimmune liver diseases from the aspects such as molecular mimicry mechanism, in order to further understand the pathogenesis of autoimmune liver diseases.

Casos clínicos de los síndromes de Guillain-Barré y Miller-Fisher relacionados con la COVID-19 / Clinical cases of Guillain-Barré and Miller-Fisher syndromes linked to COVID-19

Introducción: la enfermedad por coronavirus del 2019 (COVID-19), causada por el nuevo coronavirus SARSCoV-2, se ha asociado con el desarrollo de enfermedades neurológicas como el síndrome de Guillain-Barré (SGB) y sus variantes. En el presente trabajo se reportan dos casos de síndromes desmielizantes asociados con la COVID-19. Casos clínicos: hombre de 53 años con SGB y mujer de 29 años con la variante del síndrome de Miller-Fisher (SMF), respectivamente. Ambos presentaron los signos y síntomas neurológicos clásicos de polineuropatía desmielinizante que caracterizan a estos síndromes. De las pruebas bioquímicas paraclínicas, el aumento de proteínas en líquido cefalorraquídeo fue distintiva. La positividad de la RT-qPCR para el SARS-CoV-2 indicó la asociación de los SGB y SMF con la COVID-19. Ambos pacientes se trataron con inmunoglobulina intravenosa y mostraron mejoría. La electromiografía realizada en semanas posteriores aún mostrabaafectación desmielinizante crónica. Conclusión: los casos de los SGB y SMF, junto con otros casos similares reportados en todo el mundo, proporcionan más evidencia para el SARS-CoV-2 como nueva posible etiología de estas raras enfermedades neurológicas.

Background: coronavirus disease 2019 (COVID-19), caused by the new coronavirus SARS CoV-2, has been associated with the development of neurological diseases such as Guillain-Barré syndrome (GBS) and its variants. In the present work, two cases of demyelinating syndromes associated with COVID-19 are reported. Clinical cases: 53-year-old male with GBS and and 29-yearold female with Miller-Fisher syndrome (MFS) variant, respectively. Both patients presented the classic neurological signs and symptoms of demyelinating polyneuropathy that characterizes the syndromes. From the paraclinical biochemical tests, the increase of proteins in cerebrospinal fluid was distinctive. The positivity of the RT-qPCR for SARSCoV-2 suggested the association of GBS and MFS with COVID-19. Both patients were treated with intravenous immunoglobulin showing improvement. Electromyography performed weeks ahead still showed chronic demyelinating involvement. Conclusion: The cases of GBS and MFS, along with other similar cases reported around the world, provide further evidence for SARS-CoV-2 as a new possible etiology of these rare neurological diseases.

Is microbial infection always harmful? / 中华实验眼科杂志

It is possible for microbial infection (including parasitic infection) to disrupt the balance of autoimmune tolerance,result in the dysfunction of immune system,and make the organism encountered with the attack of the autoimmune disease.As one of the common places between foreign antigens and autoantigens,molecular mimicry is believed to play a vital role in the pathogenesis of autoimmune diseases.However,a large number of studies suggest that rather than inducing various symptoms of autoimmune diseases,many infection of microorganisms covered with mimic peptide of the autoantigen may even protect the infected organism from the disease at the level of antibodies or T cells when the analogous antigen invaded again.The present paper reviews the possible prognosis after microbial infection based on molecular mimicry.

In vitro study and molecular modeling on 17-AAG-Ioaded polymethyl methacrylate bone cement for multiple myeloma / 中华骨科杂志

Objective To explore the possibility of polymethyl methacrylate (PMMA) bone cement as the carrier for lipophilic drugs through in vitro cytotoxicity study and molecular modeling with PMMA and 17-allylamino-17-demethoxy-geldanamycin (17-AAG) loaded PMMA bone cement.Methods The 17-AAG loaded bone cement was made by mixing method.In vitro antitumor activity with MTT assay for PMMA,17-AAG,the 24 h and 48 h released solution of 17-AAG loaded PMMA bone cement were evaluated.Through Material Studio 5.0,the interaction between 17-AAG and PMMA through the model of Amorphous Cell and energy optimization of Forcite was explored.Results The inhibition ratio of MMA for tumor cells is 9.21％±0.06％ with 50 μmol/L.The 24 h released solution of 17-AAG loaded PMMA bone cement (17-AAG∶ PMMA=1∶ 4 000) inhibits the tumor cells 66.15％±0.43％ which has a quick released influence on 17-AAG.The inhibition of 24 h released solution of 17-AAG-loaded PMMA bone cement (17-AAG∶PMMA=1 ∶ 1 000,1∶2 000) shows no significance compared with PMMA released solution (P＜0.05).The 48 h released solution of 17-AAG-PMMA (17-AAG∶ PMMA=1∶ 1 000,1∶2 000,1∶4 000) inhibits U26630.25％±4.47％,30.24％±3.42％,50.52％±5.20％,with a significant difference with PMMA.The molecular model showed that the interaction between 17-AAG and PMMA was van der Waalz bonds,which drove 17-AAG inside or on the surface of PMMA bone cement.Conclusion PMMA bone cement can be used as a carrier for lipophilic drugs.It has antitumor activity and influences the release of 17-AAG with different ratio,for example it has a sustained-released influence on 17-AAG in 17-AAG-PMMA (17-AAG∶PMMA=1 ∶ 1 000,1∶2 000).Molecular model implies that 17-AAG exists inside or on the surface the PMMA bone cement through van der Waalz bonds.

Guillain-Barre´ Syndrome and Campylobacter jejuni Infection: A Review.

Guillain-Barre´ syndrome (GBS), a neurologic disease that produces ascending paralysis, affects people all over the world. Acute infectious illness precedes 50%-75% of the GBS cases. Although many infectious agents have been associated with GBS, the strongest documented association is with Campylobacter infection. The first line of evidence supporting Campylobacter infection as a trigger of GBS is anecdotal reports. The second line of evidence is serological surveys, which have demonstrated that sera from GBS patients contain anti Campylobacter jejuni antibodies, consistent with recent infection. Finally, culture studies have proven that a high proportion of GBS patients have C. jejuni in their stools at the time of onset of neurological symptoms. One of every 1058 Campylobacter infections results in GBS. Sialic acid containing lipooligosaccharides (LOS) biosynthesis gene locus are associated with GBS and the expression of ganglioside mimicking structures. GM1a was the most prevalent ganglioside mimic in GBS associated strains. Molecular mimicry between C. jejuni LOS and gangliosides in human peripheral nerves, and cross-reactive serum antibody precipitate the majority of GBS cases in Bangladesh, like worldwide.

Potential Autoepitope within the Extracellular Region of Contactin-Associated Protein-like 2 in Mice.

Aims: Implicated in autoimmune encephalitis, neuromyotonia and genetic forms of autism, here we report that contactin-associated protein-like 2 (CNTNAP2) contains a potential autoepitope within the extracellular region. Methodology: CNTNAP2 sequence-similar regions (CSSRs) from human pathogens were identified. Sera from autistic and control children were obtained and analyzed for the presence of antibodies able to bind CSSRs. One such candidate CSSR was evaluated for evidence of autoimmune responses to CNTNAP2 in a mouse model of acute infection. Results: Autistic and control children sera contained antibodies able to discrete regions of CNTNAP2. In a murine model of acute infection, a CSSR derived from the N-terminal extracellular region of CNTNAP2 resulted in anti-CNTNAP2 antibody production, proinflammatory cytokine elevation, cerebellar and cortical white matter T-cell infiltration as well as motor dysfunction. Conclusion: Taken together, these data suggest that CNTNAP2 contains a potential autoepitope within the extracellular region.

Potential Role of Bacterial Infection in Autoimmune Diseases: A New Aspect of Molecular Mimicry

Molecular mimicry is an attractive mechanism for triggering autoimmunity. In this review, we explore the potential role of evolutionary conserved bacterial proteins in the production of autoantibodies with focus on granulomatosis with polyangiitis (GPA) and rheumatoid arthritis (RA). Seven autoantigens characterized in GPA and RA were BLASTed against a bacterial protein database. Of the seven autoantigens, proteinase 3, type II collagen, binding immunoglobulin protein, glucose-6-phosphate isomerase, alpha-enolase, and heterogeneous nuclear ribonuclear protein have well-conserved bacterial orthologs. Importantly, those bacterial orthologs are also found in human-associated bacteria. The wide distribution of the highly conserved stress proteins or enzymes among the members of the normal flora and common infectious microorganisms raises a new question on how cross-reactive autoantibodies are not produced during the immune response to these bacteria in most healthy people. Understanding the mechanisms that deselect auto-reactive B cell clones during the germinal center reaction to homologous foreign antigens may provide a novel strategy to treat autoimmune diseases.

Identificación In Silico del mimetismo molecular entre Epitopes T de Neisseria meningitidis B y el proteoma humano / In Silico identification of molecular mimicry between T-Cell Epitopes of Neisseria meningitidis B and the human proteome

El objetivo del estudio fue determinar los epítopes T de cuatro de las proteínas antigénicas más frecuentes de la membrana externa de Neisseria meningitidis B e identificar los sitios más relevantes donde existe mimetismo molecular para estos epítopes en seres humanos. Para ello se realizó un estudio in silico (estudios que usan herramientas bioinformáticas) usando las bases de datos SWISS-PROT/TrEMBL SYFPEITHI y FASTA, las cuales se emplearon para la determinación de las secuencias proteicas, la predicción de los epítopes T CD4 y CD8, y la determinación del mimetismo molecular en humanos, respectivamente. Se encontró similitud molecular en varias proteínas humanas presentes en diferentes órganos y tejidos, entre ellos: hígado, piel y epitelios, cerebro, sistema linfático y testículos, destacando las encontradas en estos últimos, ya que ellas mostraron la frecuencia más alta de secuencias miméticas. Este hallazgo ayuda a comprender el éxito de N. meningitidis B para colonizar tejidos humanos, el fracaso de ciertas vacunas contra esta bacteria e incluso ayuda a explicar posibles reacciones autoimmunes asociadas a la infección o vacunación.

The objective of the study was to determine the T-cell epitopes of four of the most frequent antigenic proteins of the outer membrane of Neisseria meningitidis B, and to identify the most relevant sites for molecular mimicry with T-cell epitopes in humans. In order to do so, an in silico study -a type of study that uses bioinformatic tools- was carried out using SWISS-PROT/TrEMBL, SYFPEITHI and FASTA databases, which helped to determine the protein sequences, CD4 and CD8 T-cell epitope prediction, as well as the molecular mimicry with humans, respectively. Molecular similarity was found in several human proteins present in different organs and tissues such as: liver, skin and epithelial tissues, brain, lymphatic system and testicles. Of these, those found in testicles were more similar, showing the highest frequency of mimetic sequences. This finding shed light on the success of N. meningitidis B to colonize human tissues and the failure of certain vaccines against this bacterium, and it even helps to explain possible autoimmune reactions associated with the infection or vaccination.

A Case of Acute Motor and Sensory Axonal Neuropathy Following Hepatitis A Infection

Acute motor and sensory axonal neuropathy (AMSAN) are recently described subtypes of Guillain-Barre syndrome characterized by acute onset of distal weakness, loss of deep tendon reflexes, and sensory symptoms. A 21-yr-old male was transferred to our hospital due to respiration difficulties and progressive weakness. In laboratory findings, immunoglobulin M antibodies against hepatitis A were detected in blood and cerebrospinal fluid. The findings of motor nerve conduction studies showed markedly reduced amplitudes of compound muscle action potentials in bilateral peroneal, and posterior tibial nerves, without evidence of demyelination. Based on clinical features, laboratory findings, and electrophysiologic investigation, the patient was diagnosed the AMSAN following acute hepatitis A viral infection. The patient was treated with intravenous immunoglobulin and recovered slowly. Clinicians should consider this rare but a serious case of AMSAN following acute hepatitis A infection.

Expression and cytotoxic effect of transmembrane form of human blood group A antigen mimotope vaccine in a malignant melanoma cell line B16 / 中华皮肤科杂志

Objective To establish a stable cell line expressing transmembrane form of human blood group A antigen mimotope vaccine by transfecting malignant melanoma cell line B16, and to detect the cytotoxicity of the vaccine against melanoma cells. Methods Cultured B16 cells were classified into 4 groups, i.e.,P/F-M-pIRES group [transfected with the recombinant plasmid mimotope peptide/Fas-macrophage inflammatory protein (Mip)-pIRES], P/F-pIRES group (transfected with the recombinant plasmid mimotope peptide/FaspIRES), M-pIRES group (transfected with the recombinant plasmid Mip-pIRES), and pIRES group (transfected with the empty plasmid pIRES). B 16 cells were transfected through Lipofectamine 2000. Subsequently, RT-PCR and Western blotting were performed to detect the mRNA and protein expressions of the mimotope peptide/Fas fusion gene and Mip3β in transfected B16 cells. Cell counting kit-8 (CCK-8) was used to evaluate the vaccinemediated complement dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC)against B16 cells. Results RT-PCR yielded specific DNA fragments with expected size. Western blotting revealed the anti-A antibody-binding activity of the recombinant mimotope peptide/Fas fusion protein. Factor analysis indicated significant differences in CDC (F = 244.522, P ＜ 0.01 ) and ADCC (F = 71.593, P ＜ 0.01 )against B16 cells between the 4 groups. Group comparisons demonstrated more intense CDC and ADCC in P/FM-pIRES and P/F-pIRES groups compared with M-plRES and pIRES groups, stronger ADCC in P/F-M-pIRES group in comparison with P/F-pIRES group (F = 15.42, P ＜ 0.05), but no significant difference in CDC was observed between M-pIRES and pIRES group. Conclusions The transmembrane form of human blood group A antigen mimotope vaccine could be stably expressed in B16 cells, and mediate ADCC and CDC against B16 cells in vitro.

Antigen mimicry followed by epitope spreading: A pathogenetic trigger for the clinical morphology of lichen planus and its transition to Graham Lassueur Piccardi Little Syndrome and keratosis lichenoides chronica - Medical hypotheses or reality? / Mimetismo antigênico seguido de espalhamento de epítopos: agente desencadeador patogênico da morfologia clínica do líquen plano e de sua transição para a Síndrome de Graham-Little-Piccardi-Lassueur e para a ceratose líquenóide crônica - Hipótese médica ou realidade?

Literature data analysis, providing an exact explanation of the lichen planus pathogenesis, as well as its transition into other rare forms such as Keratosis lichenoides chronica or Graham Lassueur Piccardi Little Syndrome are scant, or totally missing. The chronological course of the disease, known in the literature as lichen planus, varies. Some patients develop Lichen planus or lichen nitidus and there is no logical explanation why. It is also not clear why single patients initially develop ulcerative lesions in the area of the mucosa and only in a few of them these lesions affect the skin. Antigen Mimicry and Epitope Spreading could be the possible pathogenic inductor in cases of lichenoid dermatoses, as well as the cause for their transition into ulcerative, exanthematous or other rare forms. The Epitope Spreading is probably not the leading pathogenetic factor in lichen planus but a phenomenon which occurs later. This manuscript analyzes some basic pathogenic aspects and presents some possible medical hypotheses regarding the heterogenic clinical picture and pathogenesis of lichen planus and lichenoid like pathologies of the skin which, in the near future should be analyzed in details in order to clarify several dilemmas the clinical dermatologist has to face.

Análises das informações disponíveis na literatura que forneçam uma explicação precisa sobre a patogênese do Líquen Plano, assim como sobre sua transição para outras formas raras da doença, como Ceratose Liquenóide Crônica ou Síndrome de Graham-Little-Piccardi- Lassueur , são raras ou inexistentes. O curso cronológico da doença, conhecida na literatura como Líquen Plano, varia. Alguns pacientes desenvolvem Líquen Plano ou Líquen Nítido e não ha uma explicação lógica do por quê. Também não está claro por que alguns pacientes inicialmente desenvolvem lesões ulcerativas na área da mucosa e em apenas alguns deles essas lesões afetam a pele. Mimetismo Antigênico ou Espalhamento de Epítopos poderiam ser fatores patogênicos indutores em casos de Dermatoses Liquenóides, e também fatores responsáveis pela transição para a forma ulcerativa, exantematosa ou outras formas raras da doença. Espalhamento de Epítopos provavelmente não é o principal fator patogênico envolvido no Líquen Plano, mas um fenômeno de ocorrência posterior.Esse manuscrito analisa alguns aspectos patogênicos básicos e apresenta algumas hipóteses médicas sobre o quadro clínico heterogênico e a patogênese do Líquen Plano e de patologias da pele do tipo liquenóide. Essas patologias devem, em um futuro próximo, ser analisadas minuciosamente a fim de esclarecer vários dilemas que o dermatologista clínico tem de enfrentar.

Identification and Characterization of Peptide Mimics of Blood Group A Antigen / 华中科技大学学报（医学）（英德文版）

In order to investigate peptide mimics of carbohydrate blood group A antigen, a phage display 12-met peptide library was screened with a monoclonal antibody against blood group A antigen, NaM87-1F6. The antibody-binding properties of the selected phage peptides were evaluated by phage ELISA and phage capture assay. The peptides were co-expressed as glutathione S-transferase (GST) fusion proteins. RBC agglutination inhibition assay was performed to assess the natural blood group A antigen-mimicking ability of the fusion proteins. The results showed that seven phage clones selected bound to NaM87-1F6 specifically, among which, 6 clones bore the same peptide sequence, EYWYCGMNRTGC and another harbored a different one QIWYERTLPFrF. The two peptides were successfully expressed at the N terminal of GST protein. Both of the fusion proteins inhibited the RBC agglutination mediated by anti-A serum in a concentration-dependent manner. These results suggested that the fusion proteins based on the selected peptides could mimic the blood group A an- tigen and might be used as anti-A antibody-adsorbing materials when immunoabsorption was applied in ABO incompatible transplantation.

Pacientes chagásicos crônicos portadores de disfunção do nódulo sinusal: a presença de anticorpos IgG com ação agonista muscarínica independe da disfunção ventricular esquerda? / Chronic Chagas disease patients with sinus node dysfunction: is the presence of IgG antibodies with muscarinic agonist action independent of left ventricular dysfunction?

Estudos mostram que anticorpos IgG agonistas muscarínicos, de pacientes chagásicos, alteram a atividade elétrica de células cardíacas in vitro. Outros consideram sua presença, e a da síndrome do nódulo sinusal, conseqüências da lesão cardíaca progressiva. Objetivou-se avaliar a relação entre os anticorpos e as disfunções nodal e ventricular esquerda, em 65 pacientes chagásicos crônicos divididos em grupo I, composto de 31 pacientes portadores da síndrome do nódulo sinusal, e grupo II, de não portadores. A análise dos dados, pelo modelo log linear, mostrou uma interdependência entre a disfunção do nódulo sinusal e os anticorpos (p=0,0021) e entre a disfunção nodal e a ventricular (p=0,0005), mas não houve relação entre esta última e os anticorpos. Idade e sexo não tiveram influência sobre as outras variáveis. Chagásicos crônicos com a síndrome do nódulo sinusal têm maior prevalência de anticorpos agonistas muscarínicos, independentemente da presença de disfunção miocárdica.

Studies have shown that muscarinic agonist IgG antibodies from Chagas disease patients alter the electrical activity of cardiac cells in vitro. Others have considered their presence, along with sinus node dysfunction, to be consequences of progressive cardiac lesions. The aim of this study was to evaluate the relationship between these antibodies and sinus node and left ventricular dysfunction in 65 chronic Chagas disease patients. These patients were divided into group I, composed of 31 patients with sinus node dysfunction, and group II, composed of the patients without this syndrome. Data analysis using the log linear model showed interdependence between sinus node dysfunction and the antibodies (p = 0.0021) and between nodal and ventricular dysfunction (p = 0.0005). However, no relationship was found between the antibodies and ventricular function. Age and sex did not influence any other variables. The chronic Chagas disease patients with sinus node dysfunction had higher prevalence of muscarinic agonist antibodies, independent of the presence of myocardial dysfunction.

Guillian-Barre Syndrome after Preceding Shingles

Guillain-Barre Syndrome (GBS) has been known to be preceded by various infections such as Campylobacter jejuni, cytomegalovirus, and so on. We have experienced a case of GBS after a preceding herpes zoster, which was complicated by GBS, which is rare. Some circumstantial and experimental clues suggest a possible causal relationship between those two. Here we report the case along with a literature review.

Detecting antibody against candida albicans mycelial-phase protein using surrogate peptides from phage display library / 中华检验医学杂志

Objective To use phage display for generating surrogate peptides of candida albicans mycelial-phase protein as mimic antigen to develop an enzyme-linked immunosorbent assay (ELISA) assay for detection of candida albicans antibodies.Methods A monoclonal antibody against candida albicans mycelial-phase protein P47, was used in this study for selecting immunoreactive peptides, mimotopes, from a 12 mer phage library.The peptides were characterized immunologically and used for coating antigen in ELISA to detect antibodies against candida albicans in the patients' serum.Results The sensitivity, specificity and replication of the ELISA assay was good enough for clinical use. The antibody was positive in all of 10 samples of patients with confirmed systemic candida albicans infection and the results were same to those obtained with the purified mycelial-phase protein P47; The positive rates in patients receiving immunosuppressive drug cyclosporin A are 33% and the healthy 2% respectively.Conclusion The surrogate peptides from a 12 mer phage library can be used in ELISA for detecting the antibodies of candida albicans P47.