Details

Autor(en) / Beteiligte

• Dulau Florea, Alina E., MD
• Braylan, Raul C., MD
• Schafernak, Kristian T., MD, MPH
• Williams, Kelli W., MD, MPH
• Daub, Janine, MSN
• Goyal, Rakesh K., MD
• Puck, Jennifer M., MD
• Rao, V. Koneti, MD
• Pittaluga, Stefania, MD, PhD
• Holland, Steven M., MD
• Uzel, Gulbu, MD
• Calvo, Katherine R., MD, PhD

Titel

Abnormal B-cell maturation in the bone marrow of patients with germline mutations in PIK3CD

Ist Teil von

• Journal of allergy and clinical immunology, 2017-03, Vol.139 (3), p.1032-1035.e6

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• To the Editor: Class IA phosphoinositide 3-kinases (PI3Ks) are lipid kinases that transduce signals received from receptor tyrosine kinases, resulting in activation of downstream effectors including AKT, mammalian target of rapamycin, and Bruton tyrosine kinase and regulation of multiple cellular processes.1 PI3K heterodimers are composed of a catalytic p110 subunit and a regulatory subunit p85.2 p110δ, 1 of 3 isoforms of the catalytic subunit, encoded by the PIK3CD gene, is preferentially expressed in leukocytes and plays a critical role in signaling via the B-cell receptor, IL-4R, and, Toll-like receptors and is therefore critical in B-cell development, activation, proliferation, differentiation, and B-cell-mediated immunity.3 Overexpression of p110δ confers oncogenic potential.4 Recently, patients were described with germline gain-of-function (GOF) mutations in PIK3CD leading to immunodeficiency, lymphoproliferation, and increased incidence of B-cell lymphomas, termed p110 delta-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency5 or activated PI3Kdelta syndrome.6 Clinical and laboratory findings in these patients include recurrent sinopulmonary bacterial infections, bronchiectasis, cytomegalovirus and EBV viremia, lymphoproliferation in tissues, progressive lymphopenia in peripheral blood, autoimmune cytopenias, and variable but mostly abnormal immunoglobulin levels with reduced total and class-switched memory B cells.