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Jordan S Orange,
Mark Ballow,
E Richard Stiehm,
Zuhair K Ballas, Javier Chinen,
Maite De La Morena,
Dinakantha Kumararatne,
Terry O Harville,
Paul Hesterberg,
Majed Koleilat,
Sean McGhee,
Elena E Perez,
Jason Raasch,
Rebecca Scherzer,
Harry Schroeder,
Christine Seroogy,
Aarnoud Huissoon,
Ricardo U Sorensen,
Rohit Katial
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ABSTRACT: A major diagnostic intervention in the consideration of many patients suspected to have primary immunodeficiency diseases (PIDDs) is the application and interpretation of vaccination. Specifically, the antibody response to antigenic challenge with vaccines can provide substantive insight into the status of human immune function. There are numerous vaccines that are commonly used in healthy individuals, as well as others that are available for specialized applications. Both can potentially be used to facilitate consideration of PIDD. However, the application of vaccines and interpretation of antibody responses in this context are complex. These rely on consideration of numerous existing specific studies, interpolation of data from healthy populations, current diagnostic guidelines, and expert subspecialist practice. This document represents an attempt of a working group of the American Academy of Allergy, Asthma & Immunology to provide further guidance and synthesis in this use of vaccination for diagnostic purposes in consideration of PIDD, as well as to identify key areas for further research.
The Journal of allergy and clinical immunology 09/2012; 130(3 Suppl):S1-24. · 9.17 Impact Factor
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ABSTRACT: Investigations of basic immunologic mechanisms and clinical studies of primary immunodeficiencies were most prevalent in 2011. Significant progress was achieved in the characterization of T(H)17 cell differentiation and associated cytokines in the setting of inflammatory disorders, HIV infection, and immunodysregulation disorders. The role of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) mutations in the pathogenesis of CVID was further described and reported to be likely mediated by impaired TACI expression affecting B-cell function. The frequency of autoimmunity in patients with partial DiGeorge syndrome was estimated at 8.5%, predominantly resulting in blood cytopenias and hypothyroidism. Several reports emphasized the presentation of neoplasias, most often lymphomas, as the first manifestation of several primary immunodeficiencies. Novel strategies for newborn screening of B-cell lymphopenia by measuring immunoglobulin κ chain-deletion recombinant excision circles and for adenosine deaminase deficiency using tandem mass spectrometry were demonstrated to be feasible at a large scale. Progress in the treatment of primary immunodeficiencies included increased success with unrelated HLA-compatible donors for hematopoietic stem cell transplantation and the development of new gene therapy approaches with improved safety features. Induced pluripotent stem cells were developed from patients with primary immunodeficiencies, providing a virtually unlimited resource for pathophysiology and gene correction studies. New findings in several of the uncommon immunodeficiencies, such as the increased susceptibility to severe viral infections caused by defects in the activation of the Toll-like receptor 3 pathway, overall contributed to the understanding of their immunologic basis and provided for the design of effective diagnostic and therapeutic strategies.
The Journal of allergy and clinical immunology 12/2011; 129(2):342-8. · 9.17 Impact Factor
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Caridad A Martinez,
Sweta Shah,
William T Shearer,
Howard M Rosenblatt,
Mary E Paul, Javier Chinen,
Kathryn S Leung,
Alana Kennedy-Nasser,
Malcolm K Brenner,
Helen E Heslop,
Hao Liu,
Meng-Fen Wu,
Imelda C Hanson,
Robert A Krance
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ABSTRACT: Matched related donor (MRD) hematopoietic stem cell transplantation (HSCT) is a successful treatment for chronic granulomatous disease (CGD), but the safety and efficacy of HSCT from unrelated donors is less certain.
We evaluated the outcomes and overall survival in patients with CGD after HSCT.
We report the outcomes for 11 children undergoing HSCT from an MRD (n = 4) or an HLA-matched unrelated donor (MUD) (n = 7); 9 children were boys, and the median age was 3.8 years (range, 1-13 years). We treated both X-linked (n = 9) and autosomal recessive (n = 2) disease. Nine children had serious clinical infections before transplantation. The conditioning regimens contained busulfan, cyclophosphamide, cytarabine, or fludarabine according to the donor used. All patients received alemtuzumab (anti-CD52 antibody). Additional graft-versus-host disease (GvHD) prophylaxis included cyclosporine and methotrexate for MUD recipients and cyclosporine and prednisone for MRD recipients.
Neutrophil recovery took a median of 16 days (range, 12-40 days) and 18 days (range, 13-24 days) for MRD and MUD recipients, respectively. Full donor neutrophil engraftment occurred in 9 patients, and 2 had stable mixed chimerism; all patients had sustained correction of neutrophil oxidative burst defect. Four patients had grade I skin acute GVHD responding to topical treatment. No patient had grade II to IV acute GvHD or chronic GvHD. All patients are alive between 1 and 8 years after HSCT.
For CGD, equivalent outcomes can be obtained with MRD or MUD stem cells, and HSCT should be considered an early treatment option.
The Journal of allergy and clinical immunology 11/2011; 129(1):176-83. · 9.17 Impact Factor
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The Journal of allergy and clinical immunology 08/2011; 128(5):1115-7.e1-3. · 9.17 Impact Factor
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Javier Chinen,
Monica Martinez-Gallo,
Wenli Gu,
Montserrat Cols,
Andrea Cerutti,
Lin Radigan,
Li Zhang,
Lorraine Potocki,
Marjorie Withers,
James R Lupski,
Charlotte Cunningham-Rundles
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ABSTRACT: Heterozygous deleterious mutations in the gene encoding the tumor necrosis factor receptor superfamily member 13b (TNFRSF13B), or transmembrane activator and CAML interactor (TACI), have been associated with the development of common variable immunodeficiency. Smith-Magenis syndrome (SMS) is a genetic disorder characterized by developmental delay, behavioral disturbances, craniofacial anomalies, and recurrent respiratory tract infections. Eighty percent of subjects have a chromosome 17p11.2 microdeletion, which includes TACI. The remaining subjects have mutations sparing this gene.
We examined TACI protein expression and function in patients with SMS to define the role of TACI haploinsufficiency in B-cell function.
We studied TACI expression and function in a cohort of 29 patients with SMS.
In patients with SMS with only 1 TACI allele, we found decreased B-cell extracellular and intracellular expression of TACI, reduced binding of a proliferation-inducing ligand, and decreased TACI-induced expression of activation-induced cytidine deaminase mRNA, but these were normal for cells from patients with SMS and 2 TACI alleles. Impaired upregulation of B-cell surface TACI expression by a Toll-like receptor 9 agonist was also observed in cells from patients with 1 TACI allele. Gene sequence analysis of the remaining TACI allele revealed common polymorphisms, with the exception of 1 patient with an amino acid change of uncertain significance. Patients with SMS with the lowest TACI expression had significantly reduced antibody responses to pneumococcal vaccine serotypes.
Our findings suggest that haploinsufficiency of the TACI gene results in humoral immune dysfunction, highlighting the role of genomic copy number variants in complex traits.
The Journal of allergy and clinical immunology 06/2011; 127(6):1579-86. · 9.17 Impact Factor
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Clinical Immunology 06/2011; 139(3):360-2. · 4.05 Impact Factor
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ABSTRACT: Reports in basic and clinical immunology in 2010 reflected the use of state-of-the-art genetic and immunologic tools to characterize the pathogenesis of immunologic diseases and the development of novel therapies directed to these conditions. B-cell biology has been explained in greater detail, significantly with lessons from the genetic defects found in the humoral immunodeficiencies. Therapeutic mAbs are given for an increasing number of indications, such as anti-CD20 antibodies or rituximab, which was initially developed for non-Hodgkin lymphomas and is currently used in diverse autoimmune and inflammatory disorders. The report of an infant with severe combined immunodeficiency (SCID) in Massachusetts detected by means of newborn screening and successfully treated with hematopoietic stem cell transplantation validated recent efforts toward newborn screening for SCID. Improvement of survival outcomes for patients with primary immunodeficiencies treated with hematopoietic stem cell transplantation was demonstrated in a large European cohort, with significant appreciation of the type of donor graft, particularly the use of HLA-matched unrelated donors for patients with non-SCID. Progress in cellular mechanisms of drug hypersensitivity included the characterization of nitroso-modified drug metabolites as potent T-cell activators and the identification of the relocation of plasmacytoid dendritic cells from blood to skin as a potential risk factor for reactivation of viral disease.
The Journal of allergy and clinical immunology 02/2011; 127(2):336-41. · 9.17 Impact Factor
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Jolan E. Walter,
Francesca Rucci,
Laura Patrizi,
Mike Recher,
Stephan Regenass,
Tiziana Paganini,
Marton Keszei,
Itai Pessach,
Philipp A. Lang,
Pietro Luigi Poliani, [......],
Hamid M. Alenezi, Javier Chinen,
Ghassan Dbaibo,
Gehad ElGhazali,
Adriano Fontana,
Srdjan Pasic,
Cynthia Detre,
Cox Terhorst,
Frederick W. Alt,
Luigi D. Notarangelo
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ABSTRACT: The contribution of B cells to the pathology of Omenn syndrome and leaky severe combined immunodeficiency (SCID) has not been
previously investigated. We have studied a mut/mut mouse model of leaky SCID with a homozygous Rag1 S723C mutation that impairs, but does not abrogate, V(D)J recombination activity. In spite of a severe block at the pro–B
cell stage and profound B cell lymphopenia, significant serum levels of immunoglobulin (Ig) G, IgM, IgA, and IgE and a high
proportion of Ig-secreting cells were detected in mut/mut mice. Antibody responses to trinitrophenyl (TNP)-Ficoll and production of high-affinity antibodies to TNP–keyhole limpet
hemocyanin were severely impaired, even after adoptive transfer of wild-type CD4+ T cells. Mut/mut mice produced high amounts of low-affinity self-reactive antibodies and showed significant lymphocytic infiltrates in peripheral
tissues. Autoantibody production was associated with impaired receptor editing and increased serum B cell–activating factor
(BAFF) concentrations. Autoantibodies and elevated BAFF levels were also identified in patients with Omenn syndrome and leaky
SCID as a result of hypomorphic RAG mutations. These data indicate that the stochastic generation of an autoreactive B cell repertoire, which is associated with
defects in central and peripheral checkpoints of B cell tolerance, is an important, previously unrecognized, aspect of immunodeficiencies
associated with hypomorphic RAG mutations.
Journal of Experimental Medicine 07/2010; 207(7):1541-1554. · 13.85 Impact Factor
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ABSTRACT: In 2009, reports on basic and clinical immunology had an increased focus on human disease mechanisms and management. The molecular pathogenesis of familial angioedema associated with estrogen was further explored to find possible factors affecting severity, including polymorphisms in enzymes and receptors related to bradykinin pathways. A placebo-controlled clinical trial of C1 esterase inhibitor concentrate in patients with hereditary angioedema demonstrated the safety of its use and its efficacy to reduce the duration of angioedema attacks. The interaction of innate immunity and adaptive responses was further examined in several reports, establishing the significant role of Toll-like receptor stimulation for the development of optimal specific antibody responses. The 2009 update of the classification of primary immunodeficiencies introduced more than 15 new genetic defects related to the immune response, including of dedicator of cytokinesis 8 (DOCK8) mutations, which are responsible for the autosomal recessive form of the hyper-IgE syndrome. Other reports expanded the clinical spectrum of disease and improved the characterization of conditions such as warts, hypogammaglobulinemia, and myelokathexis syndrome or the occurrence of mucormycosis and Serratia species infections in patients with chronic granulomatous disease. The frequent presentation of gastrointestinal disorders in patients with humoral immunodeficiencies was recognized, and recommendations for management were reviewed. Clinical research focused on severe combined immunodeficiency included the development and implementation of a state-wide newborn screening program for this condition, a desired goal considering the significant reduction of mortality rate when the diagnosis is made early before opportunistic infections occur.
The Journal of allergy and clinical immunology 03/2010; 125(3):563-8. · 9.17 Impact Factor
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Harry R Hill,
Nancy H Augustine,
Robert J Pryor,
Gudrun H Reed,
Joshua D Bagnato,
Anne E Tebo,
Jeffrey M Bender,
Brian M Pasi, Javier Chinen,
I Celine Hanson,
Martin de Boer,
Dirk Roos,
Carl T Wittwer
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ABSTRACT: High-resolution melting analysis was applied to X-linked chronic granulomatous disease, a rare disorder resulting from mutations in CYBB. Melting curves of the 13 PCR products bracketing CYBB exons were predicted by Poland's algorithm and compared with observed curves from 96 normal individuals. Primer plates were prepared robotically in batches and dried, greatly simplifying the 3- to 6-hour workflow that included DNA isolation, PCR, melting, and cycle sequencing of any positive products. Small point mutations or insertions/deletions were detected by mixing the hemizygous male DNA with normal male DNA to produce artificial heterozygotes, whereas detection of gross deletions was performed on unmixed samples. Eighteen validation samples and 22 clinical kindreds were analyzed for CYBB mutations. All blinded validation samples were correctly identified. The clinical probands were identified after screening for neutrophil oxidase activity. Nineteen different mutations were found, including seven near intron-exon boundaries predicting splicing defects, five substitutions within exons, three small deletions predicting premature termination, and four gross deletions of multiple exons. Ten novel mutations were found, including (c.) two missense (730T>A, 134T>G), one nonsense (90C>A), four splice site defects (45 + 1G>T, 674 + 4A>G, 1461 + 2delT, and 1462-2A>C), two small deletions (636delT, 1661_1662delCT), and one gross deletion of exons 6 to 8. High-resolution melting can provide timely diagnosis at low cost for effective clinical management of rare, genetic primary immunodeficiency disorders.
The Journal of molecular diagnostics: JMD 03/2010; 12(3):368-76. · 3.48 Impact Factor
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ABSTRACT: Extrinsic factors can adversely affect immune responses, producing states of secondary immunodeficiency and consequent increased risk of infections. These immunodeficiencies, which can be encountered in routine clinical practice, arise from a number of conditions, such as treatment with glucocorticoids and immunomodulatory drugs, surgery and trauma, extreme environmental conditions, and chronic infections, such as those caused by HIV. The most common cause of immunodeficiency is malnutrition, affecting many communities around the world with restricted access to food resources. Protein-calorie deficiency and micronutrient deficiencies have been shown to alter immune responses; of note, recent progress has been made in the influence of vitamin D deficiency in causing failure of immune activation. Other categories of disease that might present with secondary immunodeficiency include metabolic diseases and genetic multisystemic syndromes. The immune defects observed in secondary immunodeficiency are usually heterogeneous in their clinical presentation, and their prognosis depends on the severity of the immune defect. Management of the primary condition often results in improvement of the immunodeficiency; however, this is sometimes not possible, and the risk of infections can be reduced with prompt antimicrobial treatment and prophylaxis.
The Journal of allergy and clinical immunology 02/2010; 125(2 Suppl 2):S195-203. · 9.17 Impact Factor
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ABSTRACT: Development of the field of organ and tissue transplantation has accelerated remarkably since the human MHC was discovered in 1967. Matching of donor and recipient for MHC antigens has been shown to have a significant positive effect on graft acceptance. The roles of the different components of the immune system involved in the tolerance or rejection of grafts and in graft-versus-host disease have been clarified. These components include antibodies, antigen-presenting cells, helper and cytotoxic T-cell subsets, immune cell-surface molecules, signaling mechanisms, and cytokines. The development of pharmacologic and biological agents that interfere with the alloimmune response has had a crucial role in the success of organ transplantation. Combinations of these agents work synergistically, leading to lower doses of immunosuppressive drugs and reduced toxicity. Reports of significant numbers of successful solid-organ transplantations include those of the kidneys, liver, heart, and lung. The use of bone marrow transplantation for hematologic diseases, particularly hematologic malignancies and primary immunodeficiencies, has become the treatment of choice in many of these conditions. Other sources of hematopoietic stem cells are also being used, and diverse immunosuppressive drug regimens of reduced intensity are being proposed to circumvent the mortality associated with the toxicity of these drugs. Gene therapy to correct inherited diseases by means of infusion of gene-modified autologous hematopoietic stem cells has shown efficacy in 2 forms of severe combined immunodeficiency, providing an alternative to allogeneic tissue transplantation.
The Journal of allergy and clinical immunology 02/2010; 125(2 Suppl 2):S324-35. · 9.17 Impact Factor
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Niraj C Patel, Javier Chinen,
Howard M Rosenblatt,
I Celine Hanson,
Robert A Krance,
Mary E Paul,
Stuart L Abramson,
Lenora M Noroski,
Carla M Davis,
Filiz O Seeborg,
Samuel B Foster,
Kathryn S Leung,
Betty S Brown,
Jerome Ritz,
William T Shearer
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ABSTRACT: The effect of pretransplantation conditioning on the long-term outcomes of patients receiving hematopoietic stem cell transplantation for severe combined immunodeficiency (SCID) has not been completely determined.
We sought to assess the outcomes of 23 mostly conditioned patients with SCID and compare their outcomes with those of 25 previously reported nonconditioned patients with SCID who underwent transplantation.
In the present study we reviewed the medical records of these 23 consecutive, mostly conditioned patients with SCID who underwent transplantation between 1998 and 2007.
Eighteen patients (median age at transplantation, 10 months; range, 0.8-108 months) received haploidentical mismatched related donor, matched unrelated donor, or mismatched unrelated donor transplants, 17 of whom received pretransplantation conditioning (with 1 not conditioned); 13 (72%) patients engrafted with donor cells and survive at a median of 3.8 years (range, 1.8-9.8 year); 5 (38%) of 13 patients require intravenous immunoglobulin; and 6 of 6 age-eligible children attend school. Of 5 recipients (median age at transplantation, 7 months; range, 2-23 months) of matched related donor transplants, all 5 engrafted and survive at a median of 7.5 years (range, 1.5-9.5 year), 1 recipient requires intravenous immunoglobulin, and 3 of 3 age-eligible children attend school. Gene mutations were known in 16 cases: mutation in the common gamma chain of the IL-2 receptor (IL2RG) in 7 patients, mutation in the alpha chain of the IL-7 receptor (IL7RA) in 4 patients, mutation in the recombinase-activating gene (RAG1) in 2 patients, adenosine deaminase deficiency (ADA) in 2 patients, and adenylate kinase 2 (AK2) in 1 patient. Early outcomes and quality of life of the previous nonconditioned versus the present conditioned cohorts were not statistically different, but longer-term follow-up is necessary for confirmation.
Hematopoietic stem cell transplantation in patients with SCID results in engraftment, long-term survival, and a good quality of life for the majority of patients with or without pretransplantation conditioning.
The Journal of allergy and clinical immunology 11/2009; 124(5):1062-9.e1-4. · 9.17 Impact Factor
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The Journal of allergy and clinical immunology 03/2009; 123(4):960-2.e2. · 9.17 Impact Factor
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ABSTRACT: We reviewed selected reports in the field of basic and clinical immunology published in 2008. Research progress in the immunologic mechanisms of allergic disease included the modulation of T(H)2 responses by specific transcription factors and receptors associated with the innate immunity, underscoring the importance of the interactions between adaptive and innate immune mechanisms. Investigations of the pathophysiology of hereditary angioedema included a variety of host factors with roles in bradykinin metabolism and vasomotor activity, explaining the variable severity of the clinical presentation. The research focus in HIV infection has shifted from control of disease progression to the barriers for viral eradication, and the search for vaccine designs that provide immunity in the short window between infection and establishment of viral reservoirs. HIV-infected individuals who receive antiviral treatment develop a high incidence of asthma, resembling the inflammatory processes associated with immunoreconstitution. The correlation of molecular diagnosis and clinical presentation was analyzed in 4 relatively rare primary immunodeficiencies: hyper-IgE syndrome; immune dysfunction, polyendocrinopathy, enteropathy, X-linked disease; cartilage-hair hypoplasia; and nuclear factor-kappaB essential modulator deficiency. Studies of patients with partial DiGeorge syndrome and chronic granulomatous disease unveiled subclinical deficiencies that might have an impact in their care. Long-term outcomes from patients with severe combined immunodeficiency who received bone marrow transplants were considered successful compared with the alternative of no intervention. However, the occurrence of adverse events reinforces the need for coordinate efforts to develop optimal protocols for hematopoietic stem cell transplantation for severe immune defects.
The Journal of allergy and clinical immunology 03/2009; 123(2):328-32. · 9.17 Impact Factor
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ABSTRACT: Between 1981 and 1995, 20 children with severe combined immunodeficiency (SCID; median age at transplant, 6.5 [range, 0.5-145] mo, 12 with serious infection) were treated with haploidentical T cell-depleted (anti-CD6 antibody) bone marrow (median number of 5.7 [0.8-18.8] x 10(8) nucleated cells/kg) from mismatched related donors (MMRDs), and 5 children with SCID (median age at transplant, 1.8 [0.5-5.0] mo, 1 with serious infection) were given unmanipulated bone marrow from matched related donors (MRDs). No conditioning or graft-versus-host disease (GvHD) prophylaxis was used.
To assess the outcomes of patients with SCID who received bone marrow from MMRDs or MRDs.
We reviewed the medical records of these 25 consecutive patients with SCID (4 with Omenn syndrome).
Of the 20 patients who received bone marrow from MMRDs, 12 engrafted, 10 survived at a median age of 15.2 [10.0-19.1] years, 4 had chronic GvHD (lung, intestine, skin), 5 required intravenous immunoglobulin, and 8 attended school or college. Two of 5 patients who died had chronic GvHD, and 2 developed lymphoproliferative disease. Of the 5 patients who received bone marrow from MRDs, 5 engrafted, 5 survived at a median age of 23.3 [18.5-26] years, 1 had chronic GvHD (lung, skin), 2 required intravenous immunoglobulin, and 4 attended school or college.
Treatment of critically ill patients with SCID with anti-CD6 antibody T cell-depleted MMRD marrow resulted in an overall 50% long-term survival of patients (83% survival of those engrafted). The principal barriers to long-term survival were delay in diagnosis, life-threatening infection, failure to engraft, and chronic GvHD. Educational goals were achieved in most of the survivors.
The Journal of allergy and clinical immunology 01/2009; 122(6):1185-93. · 9.17 Impact Factor
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ABSTRACT: Partial DiGeorge syndrome (pDGS) presents with thymic hypoplasia and a variable decrease in T-cell numbers. Although lymphocyte proliferation to mitogens is generally preserved, it is uncertain whether the development of specific cellular immunity in pDGS is similarly preserved.
We sought to study the development of antigen-specific T-cell responses in patients with pDGS with regard to their initial CD3 T-cell counts.
A retrospective review of 93 patients with pDGS followed at Texas Children's Hospital Allergy and Immunology Clinic from 1991 to 2006 was performed. Serial lymphocyte proliferation to Candida and tetanus antigens was longitudinally analyzed. Antigen-specific lymphoproliferation was compared with initial patient CD3 T-cell counts of less than the 10th percentile (n = 63), the 10th to 50th percentile (n = 20), and greater than the 50th percentile (n = 10) of age-matched normal control values. Tetanus-specific IgG levels and the number of tetanus immunizations were also studied.
The median CD3 T-cell counts at baseline in all 3 groups were as follows: 10th percentile, 1188 cells/mm(3) (range, 168-3272 cells/mm(3)); 10th to 50th percentile, 2816 cells/mm(3) (range, 1484-4155 cells/mm(3)); greater than 50th percentile, 4246 cells/mm(3) (range, 2573-6481 cells/mm(3)). Thirty-one (46%) of 68 patients with pDGS who received at least 3 tetanus vaccines had persistent Candida and tetanus-specific cellular immunity, and 24 (35%) did not have immunity to either antigen. Most (22/24) of these patients had CD3 T-cell counts at presentation of less than the 10th percentile of normal values. Protective tetanus-specific IgG titers (>0.10 IU/mL) were detected in all patients tested from the age of 2 to 85 months (n = 72).
Some patients with pDGS with low CD3 T-cell counts might not have specific Candida and tetanus cellular immunity.
The Journal of allergy and clinical immunology 10/2008; 122(6):1194-9. · 9.17 Impact Factor
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The Journal of allergy and clinical immunology 09/2008; · 9.17 Impact Factor
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ABSTRACT: In 2007, there was significant progress in the area of basic immunology, including investigations that led to a better understanding of the function of antigen-presenting cells, such as the secretion of cytokines that inhibit or induce allergic inflammation on antigen stimulation. Mechanisms of IgE function were better characterized, and the clonality of IgE-producing B cells in allergic responses of monosensitized patients was demonstrated. The hygiene hypothesis was re-examined, with most of the evidence suggesting that the increase of atopy prevalence is best explained by the absence of T(H)1 responses rather than the absence of regulatory T cells. The effects of the environment in the allergic inflammation of the lung received new emphasis. Similar progress took place in the area of clinical immunology. Immune adverse reactions to drugs, such as the toxicity of carbamazepine-specific T cells and the safety and efficacy of drugs for the treatment of hereditary angioedema, were better characterized. There were advances in the molecular characterization of primary immunodeficiencies and their management, remarkably the discovery of signal transducer and activator of transcription 3 gene mutations as the cause of hyper-IgE syndrome. Long-term outcomes of bone marrow transplantation for severe combined immunodeficiencies confirmed the efficacy of this therapy.
The Journal of allergy and clinical immunology 08/2008; 122(1):36-41. · 9.17 Impact Factor
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ABSTRACT: The immune system can be adversely affected by a variety of extrinsic factors, including immunosuppressive drugs, exposure to harsh environmental conditions, hereditary disorders other than primary immunodeficiencies, and acquired metabolic disorders such as diabetic mellitus, with all of these resulting in conditions known as secondary immunodeficiencies. Perhaps the most well known secondary immunodeficiency is caused by HIV infection; however, the most prevalent cause of immunodeficiency worldwide is severe malnutrition, which affects as much as 50% of the population in some impoverished communities. The abnormalities of the immune system induced by secondary immunodeficiencies affect both the innate and the adaptive immunity, may be subtle, and are usually heterogeneous in their clinical manifestations. Treatment of the primary condition often results in the improvement of the compromised immune components of the disease complex. This article updates the concepts of some of the major categories of conditions that can potentially suppress the immune response, including HIV disease, to provide a conceptual frame to assess patients with suspected secondary deficiencies of the immune system.
The Journal of allergy and clinical immunology 03/2008; 121(2 Suppl):S388-92; quiz S417. · 9.17 Impact Factor
