Abstract:
BACKGROUND:Chronic granulomatous disease (CGD) is characterized by mutation in any one of the five genes coding NADPH oxidase components that leads to functional abnormality preventing the killing of phagocytosed microbes by affecting the progression of a respiratory burst. CGD patients have an increased susceptibility to infections by opportunistic and pathogenic organisms. Though initial diagnosis of CGD using a nitroblue tetrazolium (NBT) test or dihydrorhodamine (DHR) test is relatively easy, molecular diagnosis is challenging due to involvement of multiple genes, presence of pseudogenes, large deletions, and GC-rich regions, among other factors. The strategies for molecular diagnosis vary depending on the affected gene and the mutation pattern prevalent in the target population. There is a paucity of molecular data related to CGD for Indian population. METHOD:This report includes data for a large cohort of CGD patients (n = 90) from India, describing the diagnostic approach, mutation spectrum, and novel mutations identified. We have used mosaicism in mothers and the expression pattern of different NADPH components by flow cytometry as a screening tool to identify the underlying affected gene. The techniques like Sanger sequencing, next-generation sequencing (NGS), and Genescan analysis were used for further molecular analysis. RESULT:Of the total molecularly characterized patients (n = 90), 56% of the patients had a mutation in the NCF1 gene, 30% had mutation in the CYBB gene, and 7% each had mutation in the CYBA and NCF2 genes. Among the patients with NCF1 gene mutation, 82% of the patients had 2-bp deletion (DelGT) mutations in the NCF1 gene. In our cohort, 41 different mutations including 9 novel mutations in the CYBB gene and 2 novel mutations each in the NCF2, CYBA, and NCF1 genes were identified. CONCLUSION:Substantial number of the patients lack NCF1 gene on both the alleles. This is often missed by advanced molecular techniques like Sanger sequencing and NGS due to the presence of pseudogenes and requires a simple Genescan method for confirmation. Thus, the diagnostic approach may depend on the prevalence of affected genes in respective population. This study identifies potential gene targets with the help of flow cytometric analysis of NADPH oxidase components to design an algorithm for diagnosis of CGD in India. In Indian population, the Genescan method should be preferred as the primary molecular test to rule out NCF1 gene mutations prior to Sanger sequencing and NGS.
journal_name
J Clin Immunoljournal_title
Journal of clinical immunologyauthors
Kulkarni M,Hule G,de Boer M,van Leeuwen K,Kambli P,Aluri J,Gupta M,Dalvi A,Mhatre S,Taur P,Desai M,Madkaikar Mdoi
10.1007/s10875-018-0567-ysubject
Has Abstractpub_date
2018-11-01 00:00:00pages
898-916issue
8eissn
0271-9142issn
1573-2592pii
10.1007/s10875-018-0567-yjournal_volume
38pub_type
杂志文章abstract:PURPOSE:Adenosine deaminase (ADA) deficiency is a systemic disorder of purine metabolism. Deficiency of the purine salvage enzyme ADA leads to the build-up of the toxic metabolites, deoxyadenosine triphosphate and deoxyadenosine. ADA is ubiquitously expressed in all tissues of the body but most profoundly affects lymph...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/s10875-015-0158-0
更新日期:2015-05-01 00:00:00
abstract::The role of lymphocytes in the pathogenesis of bullous pemphigoid was examined by assaying the blister fluid obtained from bullous pemphigoid patients for the presence of the lymphokine, lymphotoxin. Blister fluids from six bullous pemphigoid were assayed on L-929 target cells for the presence of cytolytic molecules i...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/BF00915284
更新日期:1984-01-01 00:00:00
abstract::Cytokines are powerful mediator and communication molecules capable of regulating a wide spectrum of biologic functions, including immune responses. Although the role of cytokines in the pathogenesis of human disease is not yet understood, assays for cytokines have become a common feature in research and clinical labo...
journal_title:Journal of clinical immunology
pub_type: 杂志文章,评审
doi:10.1007/BF01546317
更新日期:1994-11-01 00:00:00
abstract::A patient affected with multiple myeloma displayed in the serum, urine, and cerebrospinal fluid a paraprotein with identical electrophoretic mobility. The paraprotein, which was polymeric, appeared in the serum and cerebrospinal fluid mainly as the dimer and tetramer, whereas in the urine the tetramer was predominant....
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/BF00917333
更新日期:1986-07-01 00:00:00
abstract::Persistent, generalized lymphadenopathy (PGL) is a recognized component of human immunodeficiency virus (HIV) infection. We conducted longitudinal studies of B and T cell function in seven homosexual men with HIV infection and PGL. All seven had abnormal antibody-mediated immunity as studied by sequential assessment o...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/BF00915157
更新日期:1988-01-01 00:00:00
abstract:OBJECTIVES:Gastrointestinal manifestations are frequent in patients with common variable immunodeficiency (CVID), and some of the patients present with celiac-like features. Diagnosing celiac disease (CD) in CVID however is challenging, as autoantibody detection and histopathology of the small intestine cannot reliably...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/s10875-013-9892-3
更新日期:2013-07-01 00:00:00
abstract::The acquired immunodeficiency syndrome (AIDS) is defined in clinical terms by the development of Kaposi's sarcoma and/or severe opportunistic infections in persons without predisposing conditions. A hallmark of the syndrome has been a decrease in the number of CD4+ T helper cells. The reduction in the frequency of the...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/BF00916950
更新日期:1988-11-01 00:00:00
abstract::Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency due to a defect in one of the NADPH oxidase complex subunits; 70 % of cases are X-linked, due to a CYBB mutation, resulting in defective production of gp91PHOX. Female carriers of X-linked CGD have previously been considered to be unaffected. It is...
journal_title:Journal of clinical immunology
pub_type: 杂志文章,评审
doi:10.1007/s10875-013-9939-5
更新日期:2013-11-01 00:00:00
abstract::Liver infiltrating lymphocytes (LIL) were isolated from HCV-positive (+) and HCV-negative (-) end-stage livers. Phenotypic analysis and functional studies using proliferative and lymphocytotoxic assays were performed with the isolated LIL. Two CD3+ lymphocyte populations were found in LIL using FITC anti-CD3 monoclona...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1023/a:1027326415164
更新日期:1997-03-01 00:00:00
abstract::Various factors seem to be etiologic in the susceptibility to sinopulmonary infections in ataxia-telangiectasia (A-T) patients, i.e., low serum and salivary IgA, low serum IgG2, and even aspiration of saliva. S. pneumoniae is a common pathogen responsible from pulmonary infections and impaired antibody response to pol...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1023/a:1020599810261
更新日期:1999-09-01 00:00:00
abstract::This review describes a series of studies performed in our laboratory which have focused on the activation and subsequent proliferation and differentiation of human B lymphocytes. Utilizing polyclonal signals which activate B cells by interacting with their surface membrane Ig, we have examined the events in the trans...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/BF00917136
更新日期:1984-09-01 00:00:00
abstract::Evidence for the presence of multiple shared epitopes on the target cellular antigens was found when 290 anti-Sm and anti-U1-RNP lupus sera were analyzed by immunoblotting. Forty-eight different immunoblot patterns were observed with the sera. Studies with selected antigen-affinity-purified antibodies confirmed the pr...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/BF00916822
更新日期:1989-05-01 00:00:00
abstract:PURPOSE:To assess the serum profile of factors involved in endothelial, T-cell, and fibroblast interplay in patients with Raynaud's phenomenon (RP) associated with nailfold vodeocapillaroscopy (NVC) scleroderma findings and/or systemic sclerosis (SSc) marker autoantibodies, recently labeled as early SSc patients. METH...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/s10875-014-0037-0
更新日期:2014-08-01 00:00:00
abstract::This is the second report on the continuing efforts of LAGID to increase the recognition and registration of patients with primary immunodeficiency diseases in 12 Latin American countries: Argentina, Brazil, Chile, Colombia, Costa Rica, Honduras, Mexico, Panama, Paraguay, Peru, Uruguay, and Venezuela. This report reve...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/s10875-006-9052-0
更新日期:2007-01-01 00:00:00
abstract:PURPOSE:The dysregulated expression of miRNAs in the immune system may be critical for immune responses to pathogens and evolve into the inflammation seen in sepsis. The aim of this study is to explore the important role of miRNAs in the regulation of the immune response during neonatal sepsis. METHODS:Using a microar...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/s10875-014-0004-9
更新日期:2014-04-01 00:00:00
abstract::Emotional stress is often followed by increased susceptibility to infections. One major role in the immediate immune response to infection is played by natural killer (NK) cells. This study was designed to establish whether acute psychological stress influences cellular immune functions and to elucidate the role of en...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/BF00919268
更新日期:1993-03-01 00:00:00
abstract::Severe congenital neutropenia (SCN), originally described by the Swedish pediatrician Rolf Kostmann, constitutes a heterogeneous disorder associated with a dramatic decrease of peripheral neutrophil granulocytes. Patients suffer from life-threatening bacterial infections unless treated by recombinant human granulocyte...
journal_title:Journal of clinical immunology
pub_type: 历史文章,杂志文章,评审
doi:10.1007/s10875-016-0358-2
更新日期:2017-02-01 00:00:00
abstract::We investigated the humoral (antigen-specific immunoglobulin isotypes, IgG subclasses, and avidity maturation) and cellular (antigen-specific in vitro proliferation) immune response in 18 healthy adult volunteers, following a primary and a single booster vaccination with the T-cell dependent neoantigen rabies administ...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1023/b:joci.0000010429.36461.6b
更新日期:2003-11-01 00:00:00
abstract::The effects of the addition of indomethacin and interleukin-2 (IL-2) to phytohemagglutinin (PHA)-stimulated lymphocytes from patients with untreated squamous-cell carcinoma of the lung and with chronic obstructive pulmonary disease and from normal individuals were studied. In 13 of 21 patients with lung carcinoma, the...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/BF00915506
更新日期:1985-05-01 00:00:00
abstract::Rat T lymphoblasts arrested in the G1 phase of the cell cycle by interleukin-2 (IL-2) deprivation can be forced to proceed to the S phase when they are stimulated with IL-2 or the phorbol ester phorbol 12,13-dibutyrate (PDBu). When PDBu is used as a stimulus, extracellular regulated kinase 2 (ERK2) is activated by thr...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1023/a:1027375828134
更新日期:1997-11-01 00:00:00
abstract:PURPOSE:Poikiloderma with neutropenia (PN) is a genodermatosis currently described in 77 patients, all presenting with early-onset poikiloderma, neutropenia, and several additional signs. Biallelic loss-of-function mutations in USB1 gene are detected in all molecularly tested patients but genotype-phenotype correlation...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/s10875-018-0508-9
更新日期:2018-05-01 00:00:00
abstract::The present study analyzes the role of CD28-B7-mediated costimulation during in vitro human peripheral blood memory T cell activation by influenza A virus. Inhibition studies using the B7-binding fusion protein CTLA4Ig and antibodies against CD80 and CD86 demonstrate that CTLA4Ig and anti-CD86 inhibited influenza-spec...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1023/a:1010987426835
更新日期:2001-07-01 00:00:00
abstract::IgD production by short-term human peripheral blood mononuclear cell (PBM) cultures was studied to establish the in vitro correlates of low serum IgD expression. Cells of persons with less than 3 micrograms/ml IgD in the serum, referred to as the low-serum IgD phenotype (LISP), were analyzed. Advantage was taken of re...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/BF00916005
更新日期:1987-03-01 00:00:00
abstract::Rapidly progressive glomerulonephritis (RPGN) is characterized by rapid and progressive loss of renal function and the presence of crescentic glomerulonephritis (CGN). Early diagnosis and appropriate treatment is mandatory to prevent death and/or renal failure. We have evaluated an ANCA-GBM dot-blot diagnostic test in...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1023/B:JOCI.0000029115.79266.ae
更新日期:2004-07-01 00:00:00
abstract:PURPOSE:Patients affected by primary immunodeficiency usually undergo a wide range of infections, including reactivation of latent ones. Here we report two cases suffering from late-onset combined immunodeficiency in which ulcerative enteritis due to human Cytomegalovirus caused a life-threatening malabsorption syndrom...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/s10875-014-0060-1
更新日期:2014-08-01 00:00:00
abstract::Interferon-γ receptor 1 (IFN-γR1) deficiency is one of the primary immunodeficiencies conferring Mendelian Susceptibility to Mycobacterial Disease (MSMD). Some cases of neoplasms have been recently reported in patients with MSMD, underlying the already known link between immunodeficiency and carcinogenesis. We report ...
journal_title:Journal of clinical immunology
pub_type: 杂志文章,评审
doi:10.1007/s10875-014-0098-0
更新日期:2014-11-01 00:00:00
abstract::Immune complexes and 1-O-alkyl-2-acetyl-SN-glycero-3-phosphorylcholine (AGEPC) are potent platelet-activating factors which interact with distinct receptors on human platelets. The mechanisms of platelet activation by these two stimuli were investigated by examining the effects of AGEPC on human platelets which had be...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/BF00915365
更新日期:1986-01-01 00:00:00
abstract::To compare the efficacy of immunoglobulin replacement therapy given intravenously versus subcutaneously to prevent infections in patients with primary antibody deficiency syndromes, an international, multicenter, open label, crossover study was designed. Forty patients were randomized to receive either subcutaneous or...
journal_title:Journal of clinical immunology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1023/a:1006678312925
更新日期:2000-03-01 00:00:00
abstract::Treatment decisions made in clinical practice, based on current guidelines, often conflict with decisions by third-party payors that restrict the ability of patients with primary immunodeficiency disease (PI) to adhere to appropriate treatment. This is seen by many physicians as potentially placing the health of patie...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/s10875-012-9723-y
更新日期:2012-09-01 00:00:00
abstract::MECP2 (methyl CpG binding protein 2) duplication causes syndromic intellectual disability. Patients often suffer from life-threatening infections, suggesting an additional immunodeficiency. We describe for the first time the detailed infectious and immunological phenotype of MECP2 duplication syndrome. 17/27 analyzed ...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/s10875-015-0129-5
更新日期:2015-02-01 00:00:00