ABSTRACT
TREX1 acts in the initial prevention of an autoimmune response, but it may contribute to the permissiveness of retrovirus infections. This study investigated the association between the levels of TREX1 gene expression with the polymorphisms TREX1 rs3135941 (T/C) and TREX1 rs3135945 (G/A), and the presence of antinuclear antibodies (ANA) in antiretroviral therapy (ART)-naïve individuals and after 1 year of treatment. Blood samples from 119 individuals with HIV-1 were subjected to genotyping of polymorphisms and quantification of TREX1 gene expression and HIV-1 viral load by qPCR. The concentration of IFN-α and the number of CD4+/CD8+ T lymphocytes were determined by ELISA and flow cytometry, respectively; ANA was investigated by immunofluorescence. A control group of 167 seronegative individuals was used for the comparison of genotypic frequencies. The frequency of the polymorphisms were not associated with HIV infection or with variations in the expression of TREX1 and IFN-α (p > 0.05). ART-naïve individuals exhibited higher TREX1 expression and lower IFN-α expression. After 1 year of ART, TREX1 levels were reduced, while IFN-α and CD4+ T lymphocytes were elevated (p < 0.05). Some individuals on ART presented ANA. These results suggest that ART-mediated restoration of immune competence is associated with a reduction in TREX1 expression, which may induce the development of ANA, regardless of the polymorphism investigated.
Subject(s)
Exodeoxyribonucleases , HIV Infections , HIV-1 , Immune Reconstitution , Phosphoproteins , Adult , Female , Humans , Male , Middle Aged , Antibodies, Antinuclear/blood , CD4-Positive T-Lymphocytes/immunology , Exodeoxyribonucleases/genetics , Exodeoxyribonucleases/metabolism , Genotype , HIV Infections/immunology , HIV Infections/drug therapy , HIV Infections/genetics , HIV Infections/virology , HIV-1/immunology , Immune Reconstitution/genetics , Immune Reconstitution/immunology , Interferon-alpha/blood , Interferon-alpha/metabolism , Phosphoproteins/genetics , Polymorphism, Single Nucleotide , Viral Load , Anti-Retroviral Agents/adverse effects , Anti-Retroviral Agents/therapeutic useABSTRACT
La tuberculosis es un factor de riesgo en los pacientes con sida, ya que una vez iniciado el tratamiento antirretroviral pueden de desarrollar un síndrome de reconstitución inmune, lo que favorecería el deterioro del su estado clínico. Se presenta el caso de un paciente masculino, de 24 años de edad, diagnosticado de sida hace 4 años, y tratamiento irregular con antirretrovirales. Acudió al Hospital Universitario Clínico Quirúrgico "Comandante Faustino Pérez Hernández" con fiebre elevada, acompañado de cuadro general, manifestaciones respiratorias y dolor inguinal derecho. En el examen físico se constató un cuadro adénico generalizado, fue hospitalizado para estudio y tratamiento. Se diagnosticó un síndrome de reconstitución inmune en un paciente de sida con una tuberculosis diseminada, el cual fallece a pesar de la terapéutica impuesta. Este síndrome se caracteriza por una restauración gradual de la inmunidad patógeno-específica, donde el sistema inmune es capaz de reconocer patógenos presentes pero clínicamente ocultos. Se asocia a otros factores de riesgo y puede ser letal; de ahí que el reconocimiento oportuno de los pacientes con alto riesgo de contraerlo, así como un adecuado manejo sobre cuándo iniciar la terapia antirretroviral en cada caso específico, es quizá la única forma de prevenir su desarrollo (AU).
Tuberculosis is a risk factor in patients with AIDS, because once the retroviral treatment begins they can develop an immune reconstitution syndrome that would favor the deterioration of their clinical status. The case of a male patient, aged 24 years is presented. He was diagnosed with AIDS four years ago, and was irregularly treated with antiretroviral. The patient assisted the Clinic-surgical University Hospital "Comandante Faustino Pérez Hernández" with high fever accompanied by general characteristics, respiratory manifestations and right inguinal pain. At the physical examination, generalized adenic characteristics were found. A syndrome of immune reconstitution was diagnosed in an AIDS patient with disseminated tuberculosis; the patient died in spite of the imposed therapy. This syndrome is characterized by the gradual restoration of the pathogen-specific immunity, where the immune system is able of recognizing the pathogens that are present but clinically hidden. It is associated to other risk facts and may be lethal; therefore the timely recognition of the patients at high risk of suffering it, and also an adequate management about when to begin the anti-retroviral therapy in each specific case, is the unique way of preventing its development (AU).
Subject(s)
Humans , Male , Tuberculosis/complications , Acquired Immunodeficiency Syndrome/complications , Immune Reconstitution/immunology , Tuberculosis/diagnosis , Tuberculosis/mortality , Medical Records , Acquired Immunodeficiency Syndrome/mortality , Acquired Immunodeficiency Syndrome/rehabilitation , Antiretroviral Therapy, Highly Active/mortality , Alcoholism/complicationsABSTRACT
INTRODUCTION: Chronic granulomatous disease is a primary immunodeficiency that results from mutations in proteins of the NADPH oxidase system that affect the microbicidal activity of phagocytes. Immune reconstitution by hematopoietic stem cell transplantation is currently the only curative therapy for this disease. OBJECTIVE: To describe the clinical and molecular characterization of a patient with X-linked chronic granulomatous disease and the successful immune reconstitution by means of a hematopoietic stem cell transplantation. METHODS: The respiratory burst was measured by flow cytometry using the dihydrorodamine 123 (DHR) oxidation test in neutrophils of peripheral blood. Mutational analysis of CYBB was performed by PCR amplification in complementary DNA, as well as sequencing and comparative genomic hybridization in genomic DNA. HLA-identical stem cells from the patient's younger brother were used for the transplantation and reduced intensity pre-transplantation conditioning was administered. Post-transplantation immune reconstitution was evaluated periodically by serial complete blood counts and DHR 123 in peripheral blood neutrophils. RESULTS: The diagnosis of X-linked chronic granulomatous disease resulted from a hemizygous deletion affecting Xp21.1 that included the entire CYBB. Post-transplantation engraftment was documented in platelets and peripheral blood neutrophils at days 10 and 11, respectively. Total hematological reconstitution was achieved by day 30 post-transplantation and no complications or infections have been observed in the three years since the transplantation. CONCLUSION: Hemopoietic stem cell transplantation allows for total reconstitution of the immune function related to microbicidal activity of phagocytic cells from patients with X-linked chronic granulomatous disease.