Class-Switch Recombination Defects

Durandy, Anne; Kracker, Sven

doi:10.1016/b978-0-12-405546-9.00015-7

Cited by 2 publications

(15 citation statements)

References 112 publications

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“…Deficiencies in CD40L, CD40, AID, UNG, NEMO, IkBα, ATM, and PMS2 represent the previously identified forms of CSR/HIGM syndromes. While the clinical manifestations can be variable, the HIGM phenotype can be divided into those disorders that directly affect the CD40/CD40L pathway (B- and T-cells are impacted), and those like AID, UNG, NEMO, IkBα, ATM, and PMS2 where mainly B cells are affected in the CSR/HIGM defect ( 3 , 5 – 7 ). The more relevant and comparative characteristics of these diseases are summarized in Table 1 .…”

Section: Hyper-igm Syndromesmentioning

confidence: 99%

“…The inability of mutated CD40L protein to bind to CD40 affects CD4 T-cell and B-cell interactions, impairing CSR, SHM, T-cell co-stimulation, and development of memory B cells, resulting in a combined immunodeficiency. Patients with this disorder present in infancy with recurrent sinopulmonary infections, and opportunistic infections, such as Pneumocystis jirovecii pneumonia (PJP), or Cryptosporidium -induced diarrhea and sclerosing cholangitis, which may predispose patients to tumors of the liver, pancreas or biliary tree [reviewed in ( 3 – 8 , 22 )]. In addition to the characteristic immunoglobulin findings, neutrophils can also be low.…”

Section: Hyper-igm Syndromesmentioning

confidence: 99%

“…A normal number of mature B cells is typically observed, but class-switched memory B cells are usually very low to absent. Of note, upon in vitro activation, patients' B cells are able to undergo CSR ( 3 ). Class-switched CD27 − IgA + memory B cells can still be produced, although showing limited proliferation ( 24 ) and abnormal SHM ( 25 ).…”

Section: Hyper-igm Syndromesmentioning

confidence: 99%

“…Defective CSR results in an abnormal humoral pattern known as hyper-IgM syndrome (HIGM), characterized by normal or elevated serum levels of IgM in the context of low levels of switched IgG, IgA, and IgE isotypes. A heterogeneous group of primary immunodeficiencies (PID) underlies HIGM, collectively known as CSR defects ( 1 , 3 – 8 ).…”

Section: Introductionmentioning

confidence: 99%

“…This finding suggests that PI3K GOF defects disturb CSR and therefore might be part of CSR/HIGM syndromes. As most of the known biology related to the CSR process comes from studies of PID ( 3 , 7 ), a deeper look into new defects can be instructive to the field.…”

Section: Introductionmentioning

confidence: 99%

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Class-Switch Recombination (CSR)/Hyper-IgM (HIGM) Syndromes and Phosphoinositide 3-Kinase (PI3K) Defects

et al. 2018

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Antibody production and function represent an essential part of the immune response, particularly in fighting bacterial and viral infections. Multiple immunological phenotypes can result in dysregulation of the immune system humoral compartment, including class-switch recombination (CSR) defects associated with hyper-IgM (HIGM) syndromes. The CSR/HIGM syndromes are defined by the presence of normal or elevated plasma IgM levels in the context of low levels of switched IgG, IgA, and IgE isotypes. Recently described autosomal dominant gain-of-function (GOF) mutations in PIK3CD and PIK3R1 cause combined immunodeficiencies that can also present as CSR/HIGM defects. These defects, their pathophysiology and derived clinical manifestations are described in depth. Previously reported forms of CSR/HIGM syndromes are briefly reviewed and compared to the phosphoinositide 3-kinase (PI3K) pathway defects. Diseases involving the PI3K pathway represent a distinctive subset of CSR/HIGM syndromes, presenting with their own characteristic clinical and laboratory attributes as well as individual therapeutic approaches.

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Section: Hyper-igm Syndromesmentioning

confidence: 99%

Section: Hyper-igm Syndromesmentioning

confidence: 99%

Section: Hyper-igm Syndromesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Class-Switch Recombination (CSR)/Hyper-IgM (HIGM) Syndromes and Phosphoinositide 3-Kinase (PI3K) Defects

et al. 2018

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Pulmonary complications of predominantly antibody immunodeficiencies in a tertiary lung center

Mahdaviani

Darougar

Mansouri

et al. 2018

Interventional Medicine and Applied Science

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Background and aims Respiratory infections are expressed very soon in the life in humoral immunodeficiencies and often lead to chronic irreversible complications such as bronchiectasis and chronic airflow limitation. This study was conducted to evaluate the pulmonary complications of predominantly antibody immunodeficiencies to show the benefits of timely diagnosis and appropriate therapy. Patients and methods The information of 48 patients involved with a type of predominantly antibody immunodeficiencies, including sex, type of primary immunodeficiency, age at the onset of symptoms, age at diagnosis, recurrent infections, respiratory symptoms, and pulmonary radiological and functional abnormalities were recorded and analyzed. Results In 48 patients evaluated, the mean age at diagnosis was 25.63 years. The mean diagnostic delay was estimated to be 13.62 years. The most recurring clinical manifestations, sinusitis (69.6%), otitis (43.5%), and recurrent pneumonia were the cause of frequent admissions in 68.8% of these patients. Bronchiectasis was frequently found (58.3%) in these patients mostly involving the middle and lower lobes (48.8% and 41.5%, respectively). Conclusions Respiratory complications, infectious or non-infectious, determine the prognosis of the disease in patients with predominantly antibody immunodeficiencies. Timely diagnosis and appropriate management may improve life expectancy and the quality of life in these patients.

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Class-Switch Recombination Defects

Cited by 2 publications

References 112 publications

Class-Switch Recombination (CSR)/Hyper-IgM (HIGM) Syndromes and Phosphoinositide 3-Kinase (PI3K) Defects

Class-Switch Recombination (CSR)/Hyper-IgM (HIGM) Syndromes and Phosphoinositide 3-Kinase (PI3K) Defects

Pulmonary complications of predominantly antibody immunodeficiencies in a tertiary lung center

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