[Molecular mimicry between Plasmodium sp and Guillain-Barre syndrome antigens]. / Mimetismo molecular entre el Plasmodium sp y los antígenos del síndrome de Guillain-Barre.

OBJECTIVE: Analyze the molecular mimicry between Plasmodium spp. and autoantigens associated with GBS, identifying possible antigenic epitopes. METHODS: PSI-Blast, Praline, Emboss, Protein Data Bank, Swiss Model Server, AlphaFold 2, Ellipro and PyMol 2.3 were used to search for homologies, perform alignments, obtain protein structures, and predict epitopes. RESULTS: 17 autoantigens and seven immunological targets of the peripheral nervous system were included, identifying 72 possible epitopes associated with GBS. From the proteome of Plasmodium spp. (298 proteins), only two showed similarities close to 30% with TRIM21 and BACE1, generating seven possible epitopes. CONCLUSION: No significant homologies were observed between the proteome of GBS and Plasmodium spp. The exploration of other mechanisms such as immune-mediated capillary damage, Epitope Spreading or Bystander Activation is suggested to explain the mentioned association. These findings underscore the need to clarify the etiology of autoimmune diseases and the role of pathogens. The need for experimental studies to validate these results is emphasized.

OBJETIVO: Analizar el mimetismo molecular entre Plasmodium spp. y autoantígenos asociados al SGB, identificando posibles epítopos antigénicos. MÉTODOS: Se emplearon PSI-Blast, Praline, Emboss, Protein Data Bank, Swiss Model Server, AlphaFold 2, Ellipro y PyMol 2.3 para buscar homologías, realizar alineamientos, obtener estructuras proteicas y predecir epítopos. RESULTADOS: Se incluyeron 17 autoantígenos y siete objetivos inmunológicos del sistema nervioso periférico, identificándose 72 posibles epítopos asociados al SGB. Del proteoma de Plasmodium spp. (298 proteínas), solo dos mostraron similitud cercana al 30% con TRIM21 y BACE1, generando siete posibles epítopos. CONCLUSIÓN: No se observaron homologías significativas entre el proteoma de SGB y Plasmodium spp. Se sugiere la exploración de otros mecanismos como el daño capilar inmunomediado, Epitope Spreading o Bystander Activation para explicar la asociación mencionada. Estos hallazgos subrayan la necesidad de aclarar la etiología de las enfermedades autoinmunes y el papel de los patógenos. Se enfatiza la necesidad de estudios experimentales para validar estos resultados.

Treatment of recalcitrant vitiligo by autologous non-cultured and trypsinized melanocyte grafting in the west of Iran.

BACKGROUND: Vitiligo is a common disease with a high burden, and its recalcitrant type is unresponsive to current medical treatments. Autologous non-cultured and trypsinized melanocyte grafting, which is a simple and experience-based procedure, has been suggested for the treatment of vitiligo. OBJECTIVE: To assess autologous non-cultured and trypsinised melanocyte grafting in recalcitrant vitiligo. METHODS: This clinical trial was done on 28 patients (20 females and 8 males). After demarcation and preparation of both donor and recipient sites, both sites were shaved by a curette. The materials harvested from the donor site were trypsinized and centrifuged. The resulting suspension was mixed with hyaluronic acid gel and was spread over the shaved recipient area. RESULTS: Twenty-eight patients with a total of 108 lesions and a mean age of 25.93 ± 7.11 years were included in the present study. Generalized vitiligo (57.1%) was the most common clinical type and the face and neck regions (38%) were the most frequent treated sites. Good to excellent repigmentation was seen in the face and neck, trunk, upper extremity, and genitals in 31 (57.4%), 11 (20.4%), 9 (16.7%) and 3 (5.5%) patients, respectively. Face and neck showed significantly better results (p < 0.05). STUDY LIMITATIONS: Low sample size and single-center study. CONCLUSION: Autologous non-cultured and trypsinized melanocyte grafting is a safe method with satisfactory outcomes in recalcitrant vitiligo. Appropriate training of physicians and proper use of specialists' experiences can be effective in increasing the improvement rate.

The relationship between chronic immune response and neurodegenerative damage in long COVID-19.

In the past two years, the world has faced the pandemic caused by the severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2), which by August of 2022 has infected around 619 million people and caused the death of 6.55 million individuals globally. Although SARS-CoV-2 mainly affects the respiratory tract level, there are several reports, indicating that other organs such as the heart, kidney, pancreas, and brain can also be damaged. A characteristic observed in blood serum samples of patients suffering COVID-19 disease in moderate and severe stages, is a significant increase in proinflammatory cytokines such as interferon-α (IFN-α), interleukin-1ß (IL-1ß), interleukin-2 (IL-2), interleukin-6 (IL-6) and interleukin-18 (IL-18), as well as the presence of autoantibodies against interferon-α (IFN-α), interferon-λ (IFN-λ), C-C motif chemokine ligand 26 (CCL26), CXC motif chemokine ligand 12 (CXCL12), family with sequence similarity 19 (chemokine (C-C motif)-like) member A4 (FAM19A4), and C-C motif chemokine ligand 1 (CCL1). Interestingly, it has been described that the chronic cytokinemia is related to alterations of blood-brain barrier (BBB) permeability and induction of neurotoxicity. Furthermore, the generation of autoantibodies affects processes such as neurogenesis, neuronal repair, chemotaxis and the optimal microglia function. These observations support the notion that COVID-19 patients who survived the disease present neurological sequelae and neuropsychiatric disorders. The goal of this review is to explore the relationship between inflammatory and humoral immune markers and the major neurological damage manifested in post-COVID-19 patients.

Treatment of recalcitrant vitiligo by autologous non-cultured and trypsinized melanocyte grafting in the west of Iran

Abstract Background Vitiligo is a common disease with a high burden, and its recalcitrant type is unresponsive to current medical treatments. Autologous non-cultured and trypsinized melanocyte grafting, which is a simple and experience-based procedure, has been suggested for the treatment of vitiligo. Objective To assess autologous non-cultured and trypsinised melanocyte grafting in recalcitrant vitiligo. Methods This clinical trial was done on 28 patients (20 females and 8 males). After demarcation and preparation of both donor and recipient sites, both sites were shaved by a curette. The materials harvested from the donor site were trypsinized and centrifuged. The resulting suspension was mixed with hyaluronic acid gel and was spread over the shaved recipient area. Results Twenty-eight patients with a total of 108 lesions and a mean age of 25.93 ± 7.11 years were included in the present study. Generalized vitiligo (57.1%) was the most common clinical type and the face and neck regions (38%) were the most frequent treated sites. Good to excellent repigmentation was seen in the face and neck, trunk, upper extremity, and genitals in 31 (57.4%), 11 (20.4%), 9 (16.7%) and 3 (5.5%) patients, respectively. Face and neck showed significantly better results (p < 0.05). Study limitations Low sample size and single-center study. Conclusion Autologous non-cultured and trypsinized melanocyte grafting is a safe method with satisfactory outcomes in recalcitrant vitiligo. Appropriate training of physicians and proper use of specialists' experiences can be effective in increasing the improvement rate.

Oral Dysbiosis and Autoimmunity: From Local Periodontal Responses to an Imbalanced Systemic Immunity. A Review.

The current paradigm of onset and progression of periodontitis includes oral dysbiosis directed by inflammophilic bacteria, leading to altered resolution of inflammation and lack of regulation of the inflammatory responses. In the construction of explanatory models of the etiopathogenesis of periodontal disease, autoimmune mechanisms were among the first to be explored and historically, for more than five decades, they have been described in an isolated manner as part of the tissue damage process observed in periodontitis, however direct participation of these mechanisms in the tissue damage is still controversial. Autoimmunity is affected by genetic and environmental factors, leading to an imbalance between the effector and regulatory responses, mostly associated with failed resolution mechanisms. However, dysbiosis/infection and chronic inflammation could trigger autoimmunity by several mechanisms including bystander activation, dysregulation of toll-like receptors, amplification of autoimmunity by cytokines, epitope spreading, autoantigens complementarity, autoantigens overproduction, microbial translocation, molecular mimicry, superantigens, and activation or inhibition of receptors related to autoimmunity by microorganisms. Even though autoreactivity in periodontitis is biologically plausible, the associated mechanisms could be related to non-pathologic responses which could even explain non-recognized physiological functions. In this review we shall discuss from a descriptive point of view, the autoimmune mechanisms related to periodontitis physio-pathogenesis and the participation of oral dysbiosis on local periodontal autoimmune responses as well as on different systemic inflammatory diseases.

Fundamentos fisiopatológicos para el diagnóstico de la anemia hemolítica autoinmune / Pathophysiological basics for the diagnosis of autoimmune hemolytic anemia

RESUMEN Introducción: la anemia hemolítica autoinmune es producida por anticuerpos que reaccionan con los eritrocitos propios del paciente, demostrables a través de la positividad del test de antiglobulina o prueba de Coombs directa. La clasificación de la enfermedad se basa en dos parámetros fundamentales: su etiología y las características térmicas del funcionamiento de los autoanticuerpos. Objetivo: actualizar la información científica sobre las causas y la fisiopatología de la anemia hemolítica autoinmune. Métodos: se realizó una revisión de los principales libros de texto y los artículos más recientes publicados en las principales revistas hematológicas e inmunológicas, para lograr una guía práctica del diagnóstico de la enfermedad. Discusión: debido a que existe una amplia gama de protocolos para su diagnóstico basados en parámetros no siempre coincidentes, se expone una metodología para el trabajo de los médicos que atienden enfermos con diferentes tipos de anemia hemolítica autoinmune, sobre la base de los conocimientos acerca de las causas y la fisiopatología de la enfermedad. Conclusiones: la comprensión de la fisiopatología y los criterios de clasificación de la anemia hemolítica autoinmune es un requisito para el diagnóstico de este trastorno, y la utilización de las nuevas opciones terapéuticas en el manejo de estos enfermos.

ABSTRACT Introduction: autoimmune hemolytic anemia is produced by antibodies that react with the patient's own erythrocytes provable through the positivity of the antiglobulin test or direct Coombs test. The classification of the disease is based on two fundamental parameters: its etiology and the thermal characteristics of the functioning of the auto antibodies accounts. Objective: to update scientific information on the causes and pathophysiological autoimmune hemolytic anemia. Methods: a review of the main textbooks and the most recent articles published in the main hematological and immunological journals was carried out, bringing together the knowledge to achieve a practical guide to the diagnosis of this disease. Discussion: due to the fact that there is a wide range of protocols for its diagnosis, based on parameters that do not always coincide, a methodology is presented for the work of physicians who treat patients with different types of autoimmune hemolytic anemia based on knowledge about the causes and the pathophysiological characteristics of this disease. Conclusions: understanding the physiopathology and classification criteria of autoimmune hemolytic anemia is a requirement for the diagnosis of this disorder and the use of new therapeutic options in the management of these patients.

Artritis reumatoide, autoanticuerpos y enzimas PADs / Rheumatoid arthritis, autoantibodies, and PAD enzymes

Resumen: La artritis reumatoide es una enfermedad inflamatoria sistémica que se caracteriza por sinovitis crónica y producción de autoanticuerpos. Los factores de riesgo incluyen genes HLA-DRῘβ1 con epítope compartido, periodontitis y tabaquismo. Al menos cinco diferentes sistemas de anticuerpos contra autoantígenos están implicados en la patogénesis de la enfermedad: 1) el factor reumatoide; 2) los anticuerpos a péptidos/proteínas citrulinadas (ACPAs); 3) los anticuerpos a proteínas carbamiladas (anti-Pcar); 4) los anticuerpos contra enzimas peptidilarginina desaminasas (anti-PAD2/4) y 5) los anticuerpos contra fibrinógeno citrulinado. La existencia de ACPA ha dividido a los sujetos con artritis reumatoide en dos subclases: artritis reumatoide positiva a ACPA y negativa a ACPA. Solamente los pacientes con artritis reumatoide positiva a ACPA están estrechamente relacionados con alelos HLA-DRβ1 con epítope compartido y son reconocidos por antígenos específicos de células T y células B.

Abstract: Rheumatoid arthritis is a systemic, inflammatory disease characterized by chronic synovitis and presence of autoantibodies. Risk factors include HLA-DRβ1 genes, periodontal disease and smoking. At least 5 different autoantibodies to autoantigens are implicated in the pathogenesis of this disorder: 1) rheumatoid factor; 2) autoantibodies directed against citrullinated peptides/proteins (ACPA); 3) anti-carbamilated protein antibody (anti-carP); 4) anti-peptidylarginine deiminase antibody (anti-PAD2/4), and 5) anti-citrullinated fibrinogen antibody. Patients with rheumatoid arthritis have been divided into two disease subsets: ACPA-positive rheumatoid arthritis and ACPA- negative rheumatoid arthritis. ACPA-positive rheumatoid arthritis is associated with HLA-DRβ1 shared epitope alleles and is recognized by antigen-specific T cells and B cells.

The anti-thrombotic effects of vitamin D and their possible relationship with antiphospholipid syndrome.

The importance of the immunomodulatory effects of vitamin D has recently been associated with autoimmune and chronic inflammatory diseases. Vitamin D deficiency has been linked to the development of autoimmune conditions. Antiphospholipid syndrome is an autoimmune disease characterized by thrombotic events and obstetric complications in patients with antiphospholipid antibodies. Current data show that patients with antiphospholipid syndrome have a high prevalence of vitamin D deficiency even without classic risk factors. Several studies have suggested vitamin D may have anti-thrombotic functions. In antiphospholipid syndrome, low vitamin D serum levels have been associated with thrombotic manifestations, suggesting a possible protective role of vitamin D in antiphospholipid syndrome. This literature review presents current evidence on the haemostatic functions of vitamin D and their possible relationship with the clinical manifestations of antiphospholipid syndrome.

Alopecia areata difusa e a teoria dos autoantígenos associada a melanogênese / Diffuse alopecia areata and the autoantigens-melanogenesis association theory

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

Autoinmunidad y receptores tipo Toll / Autoimmunity and toll-like receptors

La respuesta inmune innata está conformada por un conjunto de mecanismos que permiten reconocer los componentes propios del organismo y diferenciarlos de los microorganismos invasores para generar una primera línea de defensa. Este reconocimiento está mediado por diferentes receptores presentes en la superficie y en el interior de células inmunes y no inmunes; entre ellos se encuentran los siguientes: receptores tipo Toll (RTT), receptores de lectinas tipo C, receptores tipo GIR (genes inducibles por ácido retinoico) y receptores tipo Nod y NALP, que reconocen patrones moleculares asociados a microorganismos (PMAM). Gracias a esta capacidad de discriminación, adquirida evolutivamente por la inmunidad innata, se ha aceptado tradicionalmente que los procesos autoinmunes no están relacionados con esta sino con la inmunidad adquirida. Sin embargo, varios estudios han demostrado que esa teoría no es totalmente cierta y que algunos mecanismos efectores de la inmunidad innata participan en la generación de las enfermedades autoinmunes o en la potenciación de su fisiopatología. En esta revisión se estudia la contribución de la inmunidad innata a la autoinmunidad con énfasis en el papel de los receptores tipo Toll.

Autoimmunity and toll-like receptors Innate immune response consists of a set of mechanisms allowing the body to recognize its own components and to differentiate them from invasive microorganisms in order to generate a first line of defense. Such recognition is mediated by several receptors present both on the surface and inside immune and non-immune cells, among them: Toll-like receptors, C-type lectin receptors, RIG receptors (retinoic acid induciblegenes), and Nod-like and NALP receptors, all of which recognize microbe-associated molecular patterns (MAMP). Due to this discriminative ability, acquired by innate immunity in the course of evolution, it has been traditionally accepted that autoimmune processes are not related to innate immunity but to the acquired one. However, several studies have demonstrated that this theory is not entirely true and that some mechanisms of innate immunity either participate in the generation of autoimmune diseases or enhance its physiopathology. This review examines the contribution of innate immunity to autoimmunity emphasizing on the role of Toll-like receptors.

Immune system markers of neuroinflammation in patients with clinical diagnose of neuromyelitis optica / Marcadores imunológicos em pacientes com diagnóstico de neuromielite óptica

Neuromyelitis optica (NMO) is an inflammatory, demyelinating disease of the central nervous system characterized by the association of a serious myelitis and unilateral or bilateral optic neuritis. The present study aimed to analyze the immunological parameters of NMO patients with diagnosis established based on Wingerchuck et al. (1999) criteria. Production of IgG and IgA antibodies to antigens of MBP, PLP 95-116, MOG 92-106, and the cytokines interleukin-4 (IL-4) and interferon-γ (INF-γ) were assessed by Elisa assay. The cohort was formed by 28 NMO patients and a matched healthy control group. NMO patients had significant high levels of IgG to MOG (p<0.0001), PLP (p=0.0002) and MBP (p<0.0001), and solely IgA to MBP (p<0.0001). INF-γ (p=0.61) levels were similar to healthy controls. Increased production of IL-4 (p=0.0084) indicates an important role for this cytokine in the activation of Th2 regulatory cells and of the IgA producers B lymphocyte indicating activation of humoral immunity.

A neuromielite óptica (NMO) é doença inflamatória do sistema nervoso central, caracterizada por mielite aguda ou subaguda grave e neurite óptica unilateral ou bilateral. Este estudo objetiva analisar parâmetros imunológicos de pacientes com critérios de Wingerchuck et al. (1999) para NMO. O método de ELISA avaliou a produção de IgG e IgA para antígenos da proteína básica da mielina (MBP), o proteolipídeo (PLP) 95-116, a glicoproteina associada ao oligodendrócito (MOG) 92-106 e as citocinas interleucina-4 (IL-4) e interferon-gama (INF-γ). Foram incluνdos 28 pacientes com NMO pareados com controles saudáveis. Pacientes com NMO apresentaram níveis significativamente elevados de imunoglobulinas reativas dos isotipos IgG para MOG (p<0,0001), PLP (p=0,0002) e MBP (p<0,0001) e IgA somente para MBP (p<0,0001). Os níveis de INF-γ (p=0,61) foram semelhantes aos controles. A produção elevada de IL-4 (p=0,0084) indica papel importante na ativação de células regulatórias Th2 e linfócitos B produtores de IgA e da ativação da imunidade humoral.

Sclera-Specific and non-sclera-specific autoantibodies in the serum of patients with non-infectious anterior scleritis

OBJECTIVES: to study the frequency and specificity of sclera-specific and non-sclera-specific autoantibodies in the sera of patients with anterior non-infectious scleritis. METHODS: prospective study involving 25 patients examined at the sector of Cornea and External Disease of the Department of Ophthalmology and Immuno-Rheumatology Laboratory at Federal University of São Paulo/Paulista Medicine School, during one year. The diagnosis of scleritis was according to Watson and Hayreh's (1976) classification criteria. The exclusion criterion was infectious scleritis. All the patients underwent a full clinical and ophthalmologic evaluation, including serological tests for syphilis and tuberculosis investigation. The following autoantibodies were tested: rheumatoid factor, antinuclear antibodies, anticardiolipin antibodies, ANCA (anti-neutrophil cytoplasmic antibodies), anti-SS-A/Ro, anti-SS-B/La, anti-Sm, anti-DNA and anti-APF (antiperinuclear factor). For sclera-specific autoantibodies, sera of all patients were subjected to indirect immunofluorescence and Western blot assays, using human sclera from eye banks as a substrate. Sera from 25 healthy individuals were used as a normal control in the immunologic assays. RESULTS: as non-sclera-specific autoantibodies we detected one patient with positive rheumatoid factor, two patients with positive antinuclear antibodies, two patients with positive anticardiolipin antibody and two patients with positive anti-APF. Sclera-specific autoantibodies were detected by Western blot and immunofluorescence in the serum of two patients with scleritis. The two patients with sclera-specific autoantibodies did not show non-sclera-specific autoantibodies and also presented no evidence of autoimmune rheumatic disease. Normal controls were negative for all tested autoantibodies. CONCLUSIONS: Sclera-specific autoantibodies were detected solely in the serum of patients with isolated non-infectious anterior scleritis. Non-sclera-specific...

OBJETIVOS: estudar a freqüência e especificidade de auto-anticorpos contra antígenos específicos e não específicos da esclera no soro de pacientes com esclerite anterior não infecciosa. MÉTODOS: foi realizado estudo prospectivo envolvendo 25 pacientes examinados no Setor de Córnea e Doenças Externas do Departamento de Oftalmologia da Unifesp-EPM e no Laboratório de Imuno-Reumatologia da Unifesp-EPM, durante um ano. Os critérios de esclerite foram estabelecidos conforme a classificação de Watson e Hayreh (1976). Os critérios de exclusão foram as esclerites infecciosas. Todos os pacientes tiveram avaliações clínica e oftalmológica completas, incluindo exames laboratoriais para afastar doenças infecciosas como a sífilis e a tuberculose. Os seguintes auto-anticorpos foram testados: fator reumatóide, anticorpos antinucleares, anticorpos anticardiolipina, ANCA (anticorpos anticitoplasmáticos de neutrófilos), anti-SS-A/Ro, anti-SS-B/La, anti-Sm, anti-DNA e anti-APF (anticorpos antifator perinuclear). Para a pesquisa de auto-anticorpos contra antígenos específicos da esclera, o soro dos pacientes foi submetido à técnica de imunofluorescência indireta e Western-blot utilizando esclera humana obtida em banco de olhos, como substrato. Os soros de 25 pacientes hígidos foram utilizados como grupo controle nos testes imunológicos. RESULTADOS: auto-anticorpos contra antígenos não específicos da esclera foram detectados: um paciente com fator reumatóide positivo, dois pacientes com fator antinúcleo positivos, dois pacientes com anticorpos anticardiolipina positivos e dois pacientes com anti-APF. Auto-anticorpos contra antígenos específicos da esclera pela técnica de imunofluorescência indireta e Western-blot foram detectados no soro de dois pacientes com esclerite. Os dois pacientes com auto-anticorpos contra antígenos específicos da esclera não apresentavam auto-anticorpos contra antígenos não específicos da esclera nem tinham doença reumática auto-imune. Os controles...