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Biomedical subjects

Javier Chinen

Publications and source records attributed to Javier Chinen.

12 recordsLinked to original sources
PubMed2006

Use of intravenous immunoglobulin in human disease: a review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology.

Human immunoglobulin prepared for intravenous administration (IGIV) has a number of important uses in the treatment of disease. Some of these are in diseases for which acceptable treatment alternatives do not exist. In this review we have evaluated the evidence underlying a wide variety of IGIV uses and make specific recommendations on the basis of these data. Given the potential risks and inherent scarcity of IGIV, careful consideration of the indications for and administration of IGIV is warranted.

Asthma↗
PubMed2006

Advances in basic and clinical immunology.

This review comments on basic and clinical immunology articles that were published in 2005, with a focus on those that appeared in the Journal of Allergy and Clinical Immunology. In the area of basic immunology, mechanisms of the innate immune system and its interaction with the adaptive immune system were described, with special consideration to applications in biodefense strategies. T regulatory cells were further characterized in their role for the control of allergic, autoimmune, and neoplastic disorders. The function of the thymus Hassall's corpuscles was reported to be the generation of T regulatory cells. Flavonoid molecules obtained from medicinal herbs, including astilbin and epigallocatechin gallate, were discovered to have immunomodulatory properties. Advances in clinical immunology resulted from efforts to develop a newborn screening test for severe combined immunodeficiency and the elucidation of the crystal structure of the IL-2 receptor gamma chain. Mutations in the membrane receptor transmembrane activator and calcium modulator and cyclophilin ligand interactor were found in patients with common variable immunodeficiency. New therapeutic options are described, such as the use of infliximab for granulomas and GM-CSF for chronic ulcers in patients with common variable immunodeficiency. The importance of mucosal immunity in acute HIV infection is cited, as is the role of CD8+ T-cell activation in HIV disease progression in children.

Allergy and Immunology↗
PubMed2005

Basic and clinical immunology.

The authors selected articles published in the literature from January 2004 through December 2004 that were relevant to the areas of basic and clinical immunology. Several articles explored the development of TH1 or TH2 response and the role of the monocyte-T cell interaction. Others were articles describing the action of drugs commonly used in asthma to inhibit cytokine responses and the anti-inflammatory role of nonimmune pulmonary cells present in the lung. Several reports show how dendritic cells are being developed as vehicles for DNA vaccines aimed at stimulating cellular responses, an advance of great importance for HIV researchers working on vaccines, who are concerned about the different ways HIV evades the immune response. Other publications described Toll-like receptors in diverse cells, including mast cells and CD4+ T cells, for the recognition of viruses and bacteria. In the area of clinical immunology, an updated classification for primary immunodeficiencies with more than 100 identified genes responsible for these diseases and the report on the second clinical trial of gene therapy for X-linked severe combined immunodeficiency syndrome were published. Significant advances included the clinical prognosis in common variable immunodeficiency for patients presenting with lung pathology, the safety of live vaccines in partial DiGeorge syndrome, the report of patients with complete DiGeorge syndrome with the presence of peripheral blood T cells, the clinical spectrum of patients with NF-kappaB essential modifier (NEMO) gene deficiency, the publication of a consensus algorithm for the management of hereditary angioedema, and the report of immune restoration syndrome in pediatric HIV infection.

Animals↗
PubMed2004

Successes and risks of gene therapy in primary immunodeficiencies.

Several primary immunodeficiencies are under consideration for gene therapy approaches because of limitations of current standard treatment. Many primary immunodeficiencies are caused by defects in single genes expressed in blood cells; thus addition of a correct copy of the gene to hematopoietic stem cells (HSCs) can generate immune cells with restored function. HSCs can be removed from a patient, treated outside the body, and reinfused. In the last decade, significant improvements have been made in transferring genes by means of retroviruses to HSCs in vitro, and gene therapy trials for patients with X-linked severe combined immunodeficiency (XSCID) and adenosine deaminase-deficient severe combined immunodeficiency have restored immune competence. Gene therapy is actively being pursued in other immunodeficiency disorders, including chronic granulomatous disease and Wiskott-Aldrich syndrome. However, enthusiasm for the correction of XSCID by means of gene therapy has been tempered by the occurrence of 2 cases of leukemia in gene therapy recipients caused by insertion of the retroviral vector in or near the oncogene LMO2. The likelihood of retroviral insertional mutagenesis was estimated to be very low in the past on the basis of theoretic calculations and the absence of observed malignancies in animal studies and early clinical trials. Emerging new findings on retroviral integration both in the patients with XSCID and experimental animals now indicate that the insertion of retroviral sequences into the genome carries significant risk. Understanding the magnitude of risk is now a priority so that safety can be improved for future gene therapy clinical trials.

Genetic Therapy↗
PubMed2004

Advances in asthma, allergy and immunology series 2004: basic and clinical immunology.

This review highlights some of the most significant advances in basic and clinical immunology that were published from August 2002 to December 2003, focusing on manuscripts that appeared in the Journal. Articles selected were those considered most relevant to Journal readers. With regard to basic immunology, this report includes articles describing FcepsilonRI expression in mucosal Langerhans cells and type II dendritic cells, mechanisms of TH1 and TH2 regulation, the role of Foxp3 in the development of CD4+CD25+ regulatory T cells, and the increasing importance of Toll receptors in immunity. Articles related to clinical immunology that were selected include the first report of lymphocyte subsets values from a large cohort of normal children; the description of new genetic defects in primary immunodeficiencies; a description of the complications of gene therapy for X-linked severe combined immunodeficiency; a report of 79 patients with hyper-IgM syndrome; a report of the mechanism of action and complications of intravenous immunoglobulin; a report of new approaches for immunotherapy; and an article on advances in HIV infection and management, including a report of defensins, small molecules with anti-HIV properties. Also summarized is an article that studied the immune system during a prolonged stay in the Antarctic, a model for human studies on the effect of environmental conditions similar to space expeditions.

Allergy and Immunology↗
PubMed2004

Perspectives of gene therapy for primary immunodeficiencies.

PURPOSE OF REVIEW: Standard therapies for patients with severe primary immunodeficiencies include bone marrow transplantation and, for adenosine deaminase deficiency, enzyme replacement. In the last decade, gene therapy has been developed as an alternative for these conditions. We summarize the recent advances in gene therapy for primary immunodeficiencies and discuss the unexpected occurrence of leukemia in a gene therapy trial for X-linked severe combined immunodeficiency. RECENT FINDINGS: Eight of 10 infants with X-linked severe combined immunodeficiency who received autologous hematopoietic stem cells transduced with a retroviral vector carrying the IL2RG complementary DNA achieved immune reconstitution. However, the two youngest patients developed leukemic expansions of gene-corrected cells. The first case had proliferation of a gamma delta T cell clone, and the second case had three alpha beta T cell clones derived from a single transduced progenitor. Leukemic cells in both patients aberrantly expressed the LIM domain only-2 transcription factor due to retroviral vector insertions in this locus. After receiving anti-leukemic treatment one patient achieved a lasting remission, but the other relapsed. Four adenosine deaminase deficient severe combined immunodeficiency patients also developed functional immunity after receiving autologous hematopoietic stem cells transduced with the adenosine deaminase gene complementary DNA following submyeloablative chemotherapy. Chronic granulomatous disease, Wiskott-Aldrich syndrome, JAK3 deficiency and RAG2 deficiency are other immunodeficiencies being studied as candidates for gene therapy. SUMMARY: Gene therapy is a promising therapeutic option for some primary immunodeficiencies, especially when cells expressing the correct gene have a selective advantage. More clinical trials with closer patient monitoring are under way to define which patients may benefit from this approach, and strategies are being developed to understand and ultimately reduce the risk of leukemia secondary to retroviral vector insertion.

Adenosine Deaminase↗
PubMed2003

Trichosporon pullulans infection in 2 patients with chronic granulomatous disease: an emerging pathogen and review of the literature.

BACKGROUND: Chronic granulomatous disease is a genetically determined primary immunodeficiency disease in which phagocytic cells are unable to kill certain bacteria and fungi after ingestion. Manifestations include recurrent pyogenic infections caused by catalase-positive microbes. Trichosporon species are emerging as opportunistic agents that cause systemic disease in immunocompromised patients. Typically disease has been described in association with T beigelii in patients with secondary immunodeficiency, such as underlying malignancy. OBJECTIVE: The objective was to report the first 2 cases of T pullulans infection in 2 male children with chronic granulomatous disease. METHODS: The records of the 2 patients were reviewed. In addition, all cases of T pullulans infection reported in the English language literature are presented. RESULTS: This report brings to 7 the total number of cases of T pullulans reported and the first in patients with chronic granulomatous disease, one with invasive pneumonia and the other with an infected paronychium and localized cellulitis. In the 5 additional cases malignancy was the principal risk factor. CONCLUSION: T pullulans has rarely been reported as a fungal pathogen. The most prominent risk factor for the development of trichosporonosis is immunocompromise, most notably with neutropenia. Abnormally functioning neutrophils, such as with chronic granulomatous disease, may also predispose individuals to this opportunistic pathogen.

Child↗
PubMed2003

Basic and clinical immunology.

Progress in immunology continues to grow exponentially every year. New applications of this knowledge are being developed for a broad range of clinical conditions. Conversely, the study of primary and secondary immunodeficiencies is helping to elucidate the intricate mechanisms of the immune system. We have selected a few of the most significant contributions to the fields of basic and clinical immunology published between October 2001 and October 2002. Our choice of topics in basic immunology included the description of T-bet as a determinant factor for T(H)1 differentiation, the role of the activation-induced cytosine deaminase gene in B-cell development, the characterization of CD4(+)CD25(+) regulatory T cells, and the use of dynamic imaging to study MHC class II transport and T-cell and dendritic cell membrane interactions. Articles related to clinical immunology that were selected for review include the description of immunodeficiency caused by caspase 8 deficiency; a case series report on X-linked agammaglobulinemia; the mechanism of action, efficacy, and complications of intravenous immunoglobulin; mechanisms of autoimmunity diseases; and advances in HIV pathogenesis and vaccine development. We also reviewed two articles that explore the possible alterations of the immune system caused by spaceflights, a new field with increasing importance as human space expeditions become a reality in the 21st century.

Animals↗
PubMed2003

Long-term assessment of T-cell populations in DiGeorge syndrome.

BACKGROUND: Patients with DiGeorge syndrome present with a broad range of T-cell deficiency. Partial DiGeorge syndrome (pDGS) is a preferred designation for patients with detectable T-cell function. Among immunology experts, there is no uniform opinion on the necessity of T-cell precautions for pDGS patients. Few studies have addressed the natural course of their immune function over time. OBJECTIVE: The objective of this study was to describe the natural history of immune parameters in pDGS. METHODS: We reviewed the medical records of 45 pDGS patients. Peripheral blood T-cell subsets counts and percentages were recorded at 1, 6, 12, 18, 24, 30, 48, 60, 72, 96, and 120 months of age, and the rates of change of T-cell measurements over the follow-up period (slopes) were calculated for each individual. Humoral immunity was evaluated by quantification of immunoglobulins and by testing antibody titers to recall antigens. RESULTS: T-cell subsets counts from pDGS patients were generally lower than those of age-matched normal populations but were not severely depressed (ie, CD4+ T-cell percentage less than 15%). The median of the slopes for CD3+, CD4+, and CD8+ T-cell percentages were -0.7%, -0.8%, and -0.1%/month, respectively, in the first year of age and 0.1%/month for each subpopulation from 12 to 120 months of age. Lymphoproliferative responses to phytohemagglutinin were adequate at all ages. Immunoglobulin deficiencies or inadequate production of specific antibodies were not detected. CONCLUSIONS: In our pDGS patient cohort, a significant deterioration of T-cell number or function did not occur over time. Clinical implications of this finding include the possibility of discontinuing T-cell deficiency precautions and frequency of reevaluations of pDGS patients with stable and adequate immune function.

CD3 Complex↗
PubMed2002

Molecular virology and immunology of HIV infection.

Great progress has been made with respect to our understanding of the immunopathogenesis of AIDS and the infectious agent, HIV, that causes the disease. HIV, a human retrovirus with tropism for CD4(+) T cells and monocytes, induces a decrease of T-cell counts, T-cell dysfunction, and, ultimately, immunodeficiency. HIV also causes B-cell dysfunction characterized by polyclonal activation, hypergammaglobulinemia, and lack of specific antibody responses. Chemokine receptors-mainly CCR5 and CXCR4-have been found to be necessary for viral entry into the host cell, a step that can be inhibited by chemokine-related molecules that are ligands for those receptors. After HIV infection, a strong cellular immunity develops and partially controls viral replication. It can take several years for HIV infection to become clinically evident. Studies in long-term nonprogressors have shown the determinant roles of both helper and cytotoxic T cells in the control of HIV disease. Advances in HIV immunology research are currently being applied in the development of prophylactic and therapeutic vaccines.

AIDS Vaccines↗