Current Perspectives on Primary Immunodeficiency Diseases

Kumar, Arvind; Teuber, Suzanne S.; Gershwin, M. Eric

doi:10.1080/17402520600800705

Cited by 35 publications

(56 citation statements)

References 105 publications

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“…26 In addition, monosomy or major structural abnormalities of the X chromosome, as seen in Turner's syndrome 27,28 and premature ovarian failure, 29 are often characterized by autoimmune features. Following our recent findings of an enhanced monosomy X in peripheral lymphocytes of women with PBC or other autoimmune diseases 8,9 and reports of a frequent skewed XCI in women with non hepatic autoimmune diseases, [30][31][32] we have now investigated the mechanisms of X loss and XCI in 166 women with PBC, 49 with CHC and 177 healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Preferential X chromosome loss but random inactivation characterize primary biliary cirrhosis

et al. 2007

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Recent work has demonstrated enhanced X monosomy in women with primary biliary cirrhosis (PBC) as well as two other female-predominant autoimmune diseases, systemic sclerosis and autoimmune thyroid disease. To further our understanding of these events, we have investigated the mechanisms of X chromosome loss and X chromosome inactivation (XCI) in 166 women with PBC and 226 rigorously age-matched healthy and liver disease controls. X chromosome analysis and determination of loss pattern was performed by quantitative fluorescent polymerase chain reaction (QF-PCR) with 4 X-linked short tandem repeats. Further definition of the XCI was based on analysis of methylation-sensitive restriction sites. Importantly, in PBC the X chromosome loss occurs not only more frequently but also in a preferential fashion. This observation supports our thesis that the enhanced X monosomy involves only one parentally derived chromosome and is not secondary to a constitutive non random pattern of XCI. In fact, in the presence of monosomy, the lost X chromosome is necessarily the inactive homologue. Conclusion: The finding that the X chromosome loss is preferential suggests the critical involvement of X chromosome gene products in the female predisposition to PBC and also emphasizes the need to determine the parental origin of the maintained chromosome to investigate the role of imprinting. (HEPATOLOGY 2007;46:456-462.)

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Section: Discussionmentioning

confidence: 99%

Preferential X chromosome loss but random inactivation characterize primary biliary cirrhosis

et al. 2007

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“…Leukocyte adhesion deficiency (LAD) includes a group of rare inherited conditions, characterized by defects in proteins involved in leukocyte rolling, adhesion and cytoskeletal regulation [81,87]. Four types are currently recognized: LAD1 is caused by a mutation of the gene encoding the common β 2 subunit, CD18, of integrin heterodimers, and thus resulting in lack of integrin β 2 adhesion molecules in the neutrophils; LAD2 is a defect of carbohydrate fucosylation, resulting in lack of fucosylated sialyl-Lewis-X on the leukocytes and subsequent impaired binding of the leukocytes to selectin molecules of endothelial cells; LAD3 is possibly due to abnormality of Rap1, a regulatory GTPase involved in integrin activation; and the fourth type is LAD with Rac2 deficiency.…”

Section: Leukocyte Adhesion Deficiencymentioning

confidence: 99%

“…Depending on the component of the immune system which is affected most, primary immunodeficiencies are divided into broad categories, including humoral, cellular, combined humoral and cellular, phagocytic, complement, and other, well characterized immunodeficiency syndromes [20,81,87] (Table 1). For each of these disorders, the pattern of infectious organisms (bacteria, viruses, fungi, protozoa) to which increased susceptibility is observed and, often, the clinical presentation of the infection, largely depend on the underlying immune deficit.…”

Section: Introductionmentioning

confidence: 99%

“…Primary immunodeficiencies are usually diagnosed during early life, with more than 80% of cases diagnosed before the age of 20 years [93]. Thus, pediatricians bear the responsibility for initial diagnosis and management of these immune disorders in the majority of cases, which usually present as recurrent, protracted or severe infections caused by common organisms or as infections caused by opportunistic pathogens [81].…”

Section: Introductionmentioning

confidence: 99%

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Fungal infections in primary immunodeficiencies

2007

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Patients with phagocytic, cellular, combined and other primary immunodeficiencies exhibit immune deficits that confer increased susceptibility to fungal infections. A number of yeasts and moulds, most commonly Candida and Aspergillus but also Cryptococcus, Histoplasma, Paecilomyces, Scedosporium, Trichosporon, Penicillium and other, rarely isolated, fungal organisms, have been variably implicated in causing disease in patients with chronic granulomatous disease, severe combined immunodeficiency, chronic mucocutaneous candidiasis, hyper-IgE syndrome, myeloperoxidase deficiency, leukocyte adhesion deficiency, defects in the interferon-gamma/interleukin-12 axis, DiGeorge syndrome, X-linked hyper-IgM syndrome, Wiskott-Aldrich syndrome and common variable immunodeficiency. Differences in the spectrum of fungal pathogens as well as in the incidence and clinical presentation of the infections may be observed among patients, depending upon different immune disorders. Fungal infections in these individuals may occasionally be the presenting clinical manifestation of a primary immunodeficiency and can cause significant morbidity and potentially fatal outcome if misdiagnosed or mistreated. A high degree of suspicion is needed and establishment of diagnosis should actively be pursued using appropriate imaging, mycological and histological studies. A number of antifungal agents introduced over the last fifteen years, such as the lipid formulations of amphotericin B, the second-generation triazoles, and the echinocandins, increase the options for medical management of these infections. Surgery may also be needed in some cases, while the role of adjunctive immunotherapy has not been systematically evaluated. The low incidence of primary immunodeficiencies in the general population complicates single-center prospective or retrospective clinical studies aiming to address diagnostic or therapeutic issues pertaining to fungal infections in these patients.

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“…X-linked agammaglobulinaemia (XLA) is an inherited immunodeficiency disease caused by mutations in the gene coding for Bruton's tyrosine kinase (BTK) and occurs with a frequency of 1 in 250 000 males [3] . Abnormal gene expression prevents B lymphocyte differentiation and maturation in the bone marrow leading to absence of circulating antibody-producing plasma cells [4] .…”

Section: Introductionmentioning

confidence: 99%

Sustained virologic response following HCV eradication in two brothers with X-linked agammaglobulinaemia

Houlihan¹,

Storan²,

Lee³

2009

WJG

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X-linked agammaglobulinaemia (XLA) is a humoral immunodeficiency syndrome characterized from childhood by the absence of circulating B lymphocytes, absent or reduced levels of serum immunoglobulin and recurrent bacterial infections. For many affected patients, regular treatment with immunoglobulin is life saving. Hepatitis C viral (HCV) infection acquired through contaminated blood products is widely described in this patient cohort. The natural history of HCV infection in patients with XLA tends to follow a more rapid and aggressive course compared to immunocompetent individuals. Furthermore, standard anti-viral therapy appears to be less efficacious in this patient cohort. Here we report the cases of two brothers with XLA who contracted HCV through contaminated blood products. They were treated with a six month course of Interferon alpha-2b and Ribavirin. We report a sustained virologic response five years after completing treatment.

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Current Perspectives on Primary Immunodeficiency Diseases

Cited by 35 publications

References 105 publications

Preferential X chromosome loss but random inactivation characterize primary biliary cirrhosis

Preferential X chromosome loss but random inactivation characterize primary biliary cirrhosis

Fungal infections in primary immunodeficiencies

Sustained virologic response following HCV eradication in two brothers with X-linked agammaglobulinaemia

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