Hallazgo de patrones para péptidos-vacuna con capacidad de acople universal en moléculas de HLA-II / Identification of patterns for peptide-vaccines in universal capacity coupling HLA-II molecules / Identificagáo de padroes para peptídeos-vacina com capacidade de acoplamento universal em moléculas HLA-II

Partiendo del alineamiento múltiple de secuencias proteicas humanas obtenidas de las bases de datos del National Center of Biotechnology Information (NCBI) y su posterior análisis espacial tridimensional, se estableció la existencia de un patrón de acople universal para péptidos presentados por las moléculas de histocompatibilidad HLA-II (DR, DP y DQ), siendo una base para el diseño de vacunas proteicas. Estos patrones espaciales fueron claramente exhibidos por los residuos altamente conservados de los tres tipos de moléculas de HLA-II. La aplicación de este nuevo hallazgo permitió diseñar péptidos con mejores valores de acople péptido-HLA-II, que los generados por el péptido de acople universal conocido como CLIP (class Il-associated invariant chain peptide).

Starting from the multiple alignment of human protein sequences obtained from the NCBI database (National Center of Biotechnology Information) and subsequent three-dimensional spatial analysis, the existence of a pattern of universal coupling to peptides presented by MHC molecules HLA-II (DR, DP and DQ) was established, being a basis for the design of protein vaccines. These spatial patterns were clearly exhibited by highly conserved residues of the three kinds of HLA-II molecules. The application of this new finding made it possible to design peptides with better Peptide -HLA-II coupling values than those generated by the universal coupling peptide called CLIP (class II-associated invariant chain peptide).

FA partir do alinhamento múltiplo de sequéncias de proteínas humanas obtidas a partir das bases de dados do NCBI (National Center of Biotechnology Information) e análise espacial tridimensional subsequente, estabeleceu-se a existéncia de um padráo de acoplamento universal para peptídeos apresentados pelas moléculas de histocompatibilidade HLA-II (DR, DP e DQ), sendo uma base para o desenho de vacinas proteicas. Estes padroes espaciais foram claramente exibidos pelos residuos altamente conservados dos trés tipos de moléculas de HLA-II. A aplicagáo deste novo achado permitiu desenhar peptídeos com melhores valores de acoplamento peptídeo-HLA-II, do que aqueles gerados pelo peptídeo de acoplamento universal conhecido como CLIP (classe II-peptídeo associado a cadeia invariante).

Use of PCR with Sequence-specific Primers for High-Resolution Human Leukocyte Antigen Typing of Patients with Narcolepsy

BACKGROUND: Narcolepsy is a neurologic disorder characterized by excessive daytime sleepiness, symptoms of abnormal rapid eye movement (REM) sleep, and a strong association with HLA-DRB1*1501, -DQA1*0102, and -DQB1*0602. Here, we investigated the clinico-physical characteristics of Korean patients with narcolepsy, their HLA types, and the clinical utility of high-resolution PCR with sequence-specific primers (PCR-SSP) as a simple typing method for identifying DRB1*15/16, DQA1, and DQB1 alleles. METHODS: The study population consisted of 67 consecutively enrolled patients having unexplained daytime sleepiness and diagnosed narcolepsy based on clinical and neurological findings. Clinical data and the results of the multiple sleep latency test and polysomnography were reviewed, and HLA typing was performed using both high-resolution PCR-SSP and sequence-based typing (SBT). RESULTS: The 44 narcolepsy patients with cataplexy displayed significantly higher frequencies of DRB1*1501 (Pc= 0.003), DQA1*0102 (Pc=0.001), and DQB1*0602 (Pc=0.014) than the patients without cataplexy. Among patients carrying DRB1*1501-DQB1*0602 or DQA1*0102, the frequencies of a mean REM sleep latency of less than 20 min in nocturnal polysomnography and clinical findings, including sleep paralysis and hypnagogic hallucination were significantly higher. SBT and PCR-SSP showed 100% concordance for high-resolution typing of DRB1*15/16 alleles and DQA1 and DQB1 loci. CONCLUSIONS: The clinical characteristics and somnographic findings of narcolepsy patients were associated with specific HLA alleles, including DRB1*1501, DQA1*0102, and DQB1*0602. Application of high-resolution PCR-SSP, a reliable and simple method, for both allele- and locus-specific HLA typing of DRB1*15/16, DQA1, and DQB1 would be useful for characterizing clinical status among subjects with narcolepsy.

Selective migration of the human helper/inducer T-cell subset CD4+ in BCG induced arthritis

SMs were stained with a panel of monoclonal antibodies [mAbs] directed against mononuclear cellular infiltrates [MNC] and HLA DR expressing ce11s. A large number of T-cells, particularly CD4 helper/inducer subset, was detected in the perivascular areas. Mature macrophages were observed mainly in the lining layer. B-cells were detected in a small percentage in perivascular aggregate and occasional cells in connective tissue areas. Moreover, HLA-DR expressing cells were detected in a large number in perivascular and connective tissue areas. In conclusion, BCG-induced arthritis is an immune-mediated process. T-cells, especially CD4+ helper/inducer subset which showed a selective migration to SMs, are likely to have the main role immediating this type of arthritis which is regulated by HLA-DR expression

HLA-DR expression in synovial memberane of juvenile rheumatoid arthritis versus osteoarthritis

The objective of this study is to compare, by immunohistochemistry, the HLA-DR expressing cells in juvenile rheumatoid arthritis [JRA] and the early osteoarthritis [OA] synovial membranes [SMs]. Synovium was obtained by blind needle biopsy from knee joints of 13 patients with JRA and 15 with early OA. Synovial membranes were stained with a RDFR2 and ML30 monoclonal antibodies [mAbs]to assess the intensity of HLA-DR expressing cells. Significantly greater percentages of HLA-DR expressing cells were detected in rheumatoid SMs when compared with osteoarthritic SMs

Expression of human-leukocyte antigen [HLA-DR] in some salivary gland neoplasm

Twenty-one cases of benign and malignant salivary gland tumors [6 cases of pleomorphic adenoma, 3 cases of carcinoma ex-mixed tumors, 3 cases of adenoid cystic carcinoma, 2 cases of epimyoepithelial carcinoma and 4 of mucoepidermoid carcinoma were screened for anti HLA-DR using monoclonal antibody immunoperoxidase method. The current study showed that benign tumor [pleomorphic adenoma] was negative in reaction, except mild focal reaction in both epithelial and stromal elements. Malignant mixed tumors, adenoid cystic carcinoma as well as low grade mucoepidermoid carcinoma showed moderate reaction. Intermediate and high grade mucoepidermoid carcinoma expressed strong HLA-DR reaction. Such findings suggested that there is a proportional relation between the malignancy and expression of HLA-DR in the epithelial cells

¿Existe un gen específico en la fibrosis intersticial familiar? / Is there a specific gen for familiar interstitial fibrosis?

La fibrosis interstical pulmonar difusa es una enfermedads poco frecuente que ha tenido un incremento substancial en los últimos años, sin embargo, existe una forma familiar con características autosómaticas dominantes sin que hasta el momento se haya encontrado un gen específico en su transmisión. El objeto del presente trabajo es el reportar en análisis de tres generaciones en donde existieron características comunes e identificándose sistemas genéticos especificos. Se trató de una familia integrada por tres generaciones, dos de las cuales resultaron con datos clínicos radiológicos, funcionales y anatomopatológicos de fibrosis interstical difusa, los antígenos de histocompartibles clase I y II compartieron alelos parecidos (A28, Bw26, Cw3, DR4 y DQ3) en los pacientes analizados, el estudio genético denterminó un carácter autosómico dominante con penetrancia variable de lo que se concluye que lis alotipos axpresados en el sistema HLA juega un papel determinante en el desarrollo de la enfermedad.