Como entender a nomenclatura e os mecanismos de associação entre os antígenos e os alelos de histocompatibildade com as doenças

Devido ao elevado grau de polimorfismo das moléculas e genes do Complexo Principal de Histocompatibilidade e às grandes mudanças ocorridas, recentemente, nos métodos de tipificação desses marcadores, tem havido muita confusão para o não especialista, em relação ao entendimento da nomenclatura do sistema. Além disso, devido ao crescente conhecimento acerca do papel das moléculas de histocompatibilidade na função imune, os mecanismos de associação das moléculas HLA com as doenças ainda constituem tópicos bastante complexos. Esta revisão abrange esses aspectos, tentando facilitar o entendimento da nomenclatura e a relevância desses marcadores imunogenéticos na determinação de susceptibilidade ou resistência às doenças.Due to the extensive degree of polymorphism of histocompatibility molecules and alleles, the continued changing of HLA nomenclature, the large recent developments for HLA typing methods at molecular level, and the growing knowledge of the function of HLA molecules in the immune response, the issue regarding the mechanisms of HLA and disease association have yielded much confusion between the HLA non-specialists. The aim of this revision is to facilitate the comprehension of the nomenclature of the Major Histocompatibility Complex, and to overview the current status of the topic HLA and disease association

HLA-DR and HLA-DQ typing: a comparative study using serology and restriction fragment length polymorphism (RFLP) analysis

Embora as tipificações sorológicas dependam da expressão adequada de moléculas HLA de classe II, nas superfícies celulares, da viabilidade celular e da presença de um painel adequado de anti-soros, esse método tem sido utilizado há muitos anos e as tipificações por biologia molecular têm suplantado os problemas. A avaliação do polimorfismo dos genes HLA por intermédio da variação do tamanho dos fragmentos gerados pós digestão com enzimas de restrição (RFLP) foi o primeiro método molecular a ser utilizado para esse fim. A sorologia e o método utilizando RFLP definem os alelos HLA sem muita resolutividade, no entanto, o método utilizando RFLP tem sido considerado melhor do que a sorologia. Assim, neste estudo, fizemos análise das tipificações dos antígenos/alelos HLA de classe II (HLA-DR e HL-DQ), comparando os dois métodos.Serology has been used for HLA typing for many decades; however, serological typing of histocompatibility class II molecules depends on the adequate expression of these molecules on the surface of B lymphocytes, the availability of viable cells and a complete set of antisera. HLA typing at the genomic level has supplanted these pitfalls. The utilization of restriction fragment length polymorphism (RFLP) was the first approach to the HLA typing at molecular level. Although serology and RFLP methods define HLA specificities at low resolution level, RFLP has been considered to be better than serology. In this study, we performed HLA class II (HLA-DR and DQ) typing comparing these two methods

Pityriasis lichenoides: clinical and immunogenetic studies

Type of study: Prevalence study. Objectives: Despite pityriasis lichenoides is an uncommon dermatosis, we observed 12 cases in the last 3 years. By this means, we review clinical and histopathologic findings of all patients with pityriasis lichenoides seen at our Division. Furthermore, since pathogenic features of the disease are unknown, we performed HLA class I and II typings to search for possible immunogenetic markers for pityriasis lichenoides. Methods: Twenty-one patients with biopsy-proven diagnosis of pityriasis lichenoides were evaluated. HLA class I and II antigens were typed using conventional serological procedures. Results: Children and young adults were predominantly affected. Most of the cases were seen in fall and winter time. Typical disseminated lesions were observed more frequently. Both acute and chronic patterns were observed at histology. Compared to controls, the HLA-B17 antigen was overrepresented in patients (P< 0.005). Conclusions: Although pityriasis lichenoides remains a cutaneous disease of undetermined origin, our findings show that the disease is associated with the HLA-B17 antigen. .Modelo de estudo:Estudo de prevalência. Objetivos: Embora a pitiríase liquenóide seja uma dermatose incomum, 12 casos foram por nós observados nos últimos três anos. Assim, neste estudo, avaliamos os perfis clínicos e histopatológicos dos pacientes com pitiríase liquenóide, atendidos na Divisão de Dermatologia. Além disso, tipificamos os antígenos HLA de classes I e II nesses pacientes.Metodologia: Foram estudados 21 pacientes com diagnóstico clínico e histopatológico de pitiríase liquenóide. As tipificações dos antígenos de histocompatibilidade de classes I e II foram realizadas, utilizando-se métodos sorológicos. Resultados: A maioria dos casos ocorreu entre crianças e ou adultos jovens, no outono e inverno. As lesões típicas de forma disseminada foram as mais freqüentes. Os achados histopatológicos mostraram lesões dos tipos agudo e crônico. O antígeno HLA-B17 estava significantemente aumentado nos pacientes em relação aos controles (P<0,005).Conclusões: Embora a etiologia da pitiríase liquenóide não seja conhecida, os achados aqui relatados mostram que o marcador HLA-B17 é prevalente entre os doentes

The influence of human papillomavirus type and HIV status on the lymphomononuclear cell profile in patients with cervical intraepithelial lesions of different severity

Abstract\ud \ud \ud \ud Background\ud \ud Immunological alterations are implicated in the increased prevalence of high-grade squamous intraepithelial lesions (HG-SIL) and persistent human papillomavirus (HPV) infection. This study evaluated the expression of CD4, CD8, CD25 (IL-2Rα) and CD28 antigens from SIL biopsies, stratified by HIV status and HPV-type. Biopsies specimens from 82 (35 HIV+) women with a normal cervix, low-grade (LG-SIL) or high-grade lesions (HG-SIL) were studied. CD molecule expression was evaluated by immunohistochemistry and HPV detection/typing performed using PCR techniques.\ud \ud \ud \ud Results\ud \ud CD4 stromal staining was increased in patients with HPV18. Women with HPV16 infection showed decreased: a) CD8 and CD25 stromal staining, b) CD25 staining in LG-SIL epithelium and in HG-SIL stroma. In HIV- women samples, CD28 epithelial staining and CD8 stromal staining surrounding metaplastic epithelium were less intense and even absent, as compared to HIV+ women. Both epithelial and stromal CD8 staining was more intense in the HG-SIL/HIV+ group than in the HG-SIL/HIV- group. Positive correlations were observed between CD4/CD25, CD4/CD28 and CD25/CD28 in the stroma and CD25/CD28 in the epithelium.\ud \ud \ud \ud Conclusion\ud \ud HIV status and HPV-type may influence the lymphomononuclear cell profile present in the spectrum of cervical lesions. The knowledge of the infiltrating cell profile in cervical tumours may help the development of specific anti-tumoural strategies.We wish to thank Ana Maria Anselmi Dorigan for excellent technical assistance.We wish to thank Ana Maria Anselmi Dorigan for excellent technical assistance.Financial support: FAPESP (01/029082 – MA Gonçalves).Financial support: FAPESP (01/02908-2 – MA Gonçalves)

Transcriptional and Posttranscriptional Regulations of the HLA-G

HLA-G has a relevant role in immune response regulation. The overall structure of the HLA-G coding region has been maintained during the evolution process, in which most of its variable sites are synonymous mutations or coincide with introns, preserving major functional HLA-G properties. The HLA-G promoter region is different from the classical class I promoters, mainly because (i) it lacks regulatory responsive elements for IFN-γ and NF-κB, (ii) the proximal promoter region (within 200 bases from the first translated ATG) does not mediate transactivation by the principal HLA class I transactivation mechanisms, and (iii) the presence of identified alternative regulatory elements (heat shock, progesterone and hypoxia-responsive elements) and unidentified responsive elements for IL-10, glucocorticoids, and other transcription factors is evident. At least three variable sites in the 3′ untranslated region have been studied that may influence HLA-G expression by modifying mRNA stability or microRNA binding sites, including the 14-base pair insertion/deletion, +3142C/G and +3187A/G polymorphisms. Other polymorphic sites have been described, but there are no functional studies on them. The HLA-G coding region polymorphisms might influence isoform production and at least two null alleles with premature stop codons have been described. We reviewed the structure of the HLA-G promoter region and its implication in transcriptional gene control, the structure of the HLA-G 3′UTR and the major actors of the posttranscriptional gene control, and, finally, the presence of regulatory elements in the coding region

Development of Type 1 Diabetes Mellitus in Nonobese Diabetic Mice Follows Changes in Thymocyte and Peripheral T Lymphocyte Transcriptional Activity

As early as one month of age, nonobese diabetic (NOD) mice feature pancreatic infiltration of autoreactive T lymphocytes, which destruct insulin-producing beta cells, producing autoimmune diabetes mellitus (T1D) within eight months. Thus, we hypothesized that during the development of T1D, the transcriptional modulation of immune reactivity genes may occur as thymocytes mature into peripheral T lymphocytes. The transcriptome of thymocytes and peripheral CD3+ T lymphocytes from prediabetic or diabetic mice analyzed through microarray hybridizations identified 2,771 differentially expressed genes. Hierarchical clustering grouped mice according to age/T1D onset and genes according to their transcription profiling. The transcriptional activity of thymocytes developing into peripheral T lymphocytes revealed sequential participation of genes involved with CD4+/CD8+ T-cell differentiation (Themis), tolerance induction by Tregs (Foxp3), and apoptosis (Fasl) soon after T-cell activation (IL4), while the emergence of T1D coincided with the expression of cytotoxicity (Crtam) and inflammatory response genes (Tlr) by peripheral T lymphocytes

Clinical manifestations of systemic lupus erythematosus: diagnostic and therapeutic approach in the emergency room

O Lúpus Eritematoso Sistêmico (LES) é uma doença auto-imune, que cursa com variado conjunto de manifestações clínicas. Entre estas, algumas podem levar o paciente a procurar um serviço de urgência. É importante que o clínico geral saiba realizar a abordagem inicial do tipo de paciente, principalmente nos casos em que manifestações graves do LES constituem ameaça imediata à vida do doente. O objetivo desta revisão é discutir o diagnóstico clínico e laboratorial das manifestações dessa patologia,que exigem conduta de urgência. São descritas as formas graves de lesões cutâneas, renais, neuropsiquiátricas, gastrointestinais, pulmonares, cardíacas e hematológicas pelo LES. A terapêutica de tais manifestações é delineada a seguir, bem como todos os cuidados necessários no seguimento inicial. A abordagem do LES, na sala de urgência, apresenta-se como um dos maiores problemas pela dificuldade de diferenciação entre a atividade da doença e o quadro infeccioso subjacente. Descartar infecção é condição indispensável para que se possa iniciar o tratamento do LES, principalmente com medicação imunossupressora. Assim, não devem ser poupados esforços para se alcançar um diagnóstico acurado das manifestações do LES, na urgência, evitando-se erros de julgamento que possam ter conseqüências desastrosas.Systemic Lupus Erythematosus (SLE) is an autoimmune disease with a diverse array of clinical manifestations. Some of them can bring the patient to urgency medical attention. It is important that the general clinician knows how to carry out the initial approach in this kind of patient, mainly in the cases with life-threatening manifestations of SLE. The purpose of this review is to discuss the manifestations of SLE that require urgency care. We describe severe forms of skin, renal, neuropsychiatry, gastrointestinal, pulmonary, cardiac and hematological involvements in SLE. The therapeutic aspects are described as well as the necessary care procedures in the initial follow-up of the patient. The principal difficulty of the management of SLE in the emergency room is differentiate disease activity from underlying infection. It is necessary to rule out infection before initiate immunosuppressive treatment. Thus, we should make an effort to obtain correct diagnosis of SLE manifestations in the emergency room, avoiding judgment mistakes that could be disastrous

Antígenos HLA na febre reumática

Antígenos HLA de classe I (HLA-A e HLA-B) e II (HLA-DR) foram tipificados em um grupo de 91 pacientes com as principais formas de apresentação da febre reumática, ou seja, coréia, cardite ou artrite. Desses pacientes, 33 tinham apenas coréia, 26 apenas cardite, 16 apenas artrite e 16 cardite e artrite. Os antígenos HLA foram tipificados, utilizando-se o teste de microlinfocitotoxicidade dependente de complemento. As freqüências dos antígenos HLA-B49 e HLA-DR1 estavam significantemente aumentadas nos pacientes, quando considerados como um todo, e, ainda, em todos os subgrupos estudados, excetuando-se aquele com coréia, no qual a freqüência do antígeno HLA-DR1 não estava aumentada. Esses resultados indicam que a susceptibilidade imunogenética à febre reumática pode variar de acordo com as manifestações clínicas, apresentadas pelos pacientes.In this study we typed HLA class I and II antigens in a series of patients presenting with the distinct major clinical manifestations of rheumatic fever (RF), i.e, chorea, carditis or arthritis. Ninety-one patients with RF were evaluated for HLA-A, -B and -DR antigens. Thirty- three had pure chorea, 26 pure carditis, 16 pure arthritis, and 16 carditis plus arthritis. HLA antigens were typed by a complement-dependent microlymphocytotoxicity assay. HLA-B49 and HLA-DR1 antigens were overrepresented in the total group of patients with RF and in all the subgroups studied, excluding the chorea subgroup in which the frequency of HLA-DR1 antigen was not increased. The results reported here indicate that immunogenetic susceptibility to RF may vary according to the major clinical manifestation presented by the patient