RESUMEN
Human Immunodeficiency Virus (HIV) infection is among the most challenging issues in the healthcare system, presenting significant financial and hygiene problems with a wide range of clinical manifestations. Despite the hopeful outcomes of Antiretroviral Therapies (ARTs), the current strategies for the treatment of patients with HIV infection have not shown clinical significance for all subjects, which is mainly due to the complexity of the disease. Therefore, the need for collaborative and interdisciplinary research focused on deciphering the multifaceted cellular, and molecular immunopathogenesis of HIV remains essential in the development of innovative and more efficacious therapeutic approaches. T-regulatory (Treg) cells function as suppressors of effector T-cell responses contributing to the inhibition of autoimmune disorders and the limitation of chronic inflammatory diseases. Notably, these cells can play substantial roles in regulating immune responses, immunopathogenesis, viral persistence and disease progression, and affect therapeutic responses in HIV patients. In this review, we aim elucidating the role of T-regulatory cells (Tregs) in the immunopathogenesis of HIV, including immunological fatigue and seroconversion. In particular, the focus of the current study is exploration of novel immunotherapeutic approaches to target HIV or related co-infections.
RESUMEN
BACKGROUND: Fanconi anemia (FA) is a rare genetic syndrome characterized by developmental defects, bone marrow failure, and a high cancer risk. FA is usually inherited as an autosomal recessive condition. This disease is genetically heterogeneous and mutations in 16 different genes have been identified in FA patients to date. An accurate diagnosis needs detection of pathogenic variations in the FA genes along with positive results from chromosome breakage test. METHODS: In this study, 48 families with at least 2 affected FA patients and positive chromosome breakage test were enrolled from the Iranian population. Molecular analysis of FA genes was performed using Next Generation Sequencing (NGS) method and Multiple Ligation Dependent Probe Amplification (MLPA). RESULTS: Causal mutations for 30 (63%) patients were identified in homozygous or compound heterozygous forms. FANCA had the highest mutation frequency rate (83%) followed by FANCG (10%), FANCD2 (3%) and FANCL (3%). A significant proportion (44%) of FANCA mutations were large rearrangements. CONCLUSION: Genetic testing for FA patients improves the accuracy of diagnosis and also will be essential for genetic counselling and prenatal diagnosis for future pregnancies in the family. Availability of NGS technology has made the screening of all known FA genes at once more practical and affordable.
Asunto(s)
Proteínas del Grupo de Complementación de la Anemia de Fanconi/genética , Anemia de Fanconi/genética , Mutación , Adulto , Preescolar , Rotura Cromosómica , Análisis Mutacional de ADN , Anemia de Fanconi/diagnóstico , Femenino , Pruebas Genéticas , Humanos , Irán , MasculinoRESUMEN
BACKGROUND: We have investigated the efficacy of QF-PCR for the prenatal recognition of common aneuploidy and compared our findings with cytogenetic results in our laboratories. METHODS: A total of 4058 prenatal samples (4031 amniotic fluid and 27 chorionic villous samples) were analyzed by QF-PCR using several selected STR markers together with amelogenin. Results were compared to those obtained by conventional cytogenetic analysis. RESULTS: We detected 139 (3.42%) numerical abnormalities in our subjects by QF-PCR. Concordant QF-PCR and karyotype results were obtained in 4001 (98.59%) of the samples. An abnormal karyotype associated with adverse clinical outcome undetected by QF-PCR was found in 16.66% (n = 28) of samples. Using QF-PCR alone, we were able to detect abnormalities in 98.59% of all referred families; however the karyotyping results improved the detection rate to 99.85% of the referred cases. Individuals with neonatal screening result with 1:10 risk ratio showed 11.29% abnormal karyotype while this number was 2.16% in mothers with risk ratio of 1:250 or less. CONCLUSION: In countries where large scale conventional cytogenetic is hampered by its high cost and lack of technical expertise, QF-PCR may be used as the first line of screening for detection of chromosomal abnormalities. We also recommend QF-PCR for all the families that are seeking prenatal diagnosis of single gene disorders aneuploidies screening to be added to their work up.