The Journal of allergy and clinical immunology · 2014
Classification of common variable immunodeficiencies using flow cytometry and a memory B-cell functionality assay.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Rösel Amelia L, Scheibenbogen Carmen, Schliesser Ulrike, Sollwedel André, Hoffmeister Bodo, Hanitsch Leif, von Bernuth Horst, Krüger Renate, Warnatz Klaus, Volk Hans-Dieter, Thomas Sybill
Аннотация
BACKGROUND: The population of patients with common variable immunodeficiency (CVID) comprises a heterogeneous group of patients with different causes of hypogammaglobulinemia predisposing to recurrent infections, higher incidence of autoimmunity, and malignancy. Although memory B cells (memBcs) are key players in humoral defense and their numbers are commonly reduced in these patients, their functionality is not part of any current classification.
OBJECTIVE: We established and validated a memBc enzyme-linked immunosorbent spot (ELISpot) assay that reveals the capacity of memBcs to develop into antibody-secreting cells and present an idea for a new classification based on this functional capacity.
METHODS: The memBc ELISpot assay, combined with flow cytometry, was applied to patients with confirmed CVID in comparison with age-matched healthy control subjects.
RESULTS: Ex vivo frequency of IgG-, IgM-, and IgA-secreting plasmablasts was significantly diminished by 27.2-, 2.4-, and 23.3-fold, respectively, compared with that seen in healthy control subjects. Moreover, in vitro differentiation of memBcs into antibody-secreting cells was 6.1-, 2.6-, and 3.7-fold significantly reduced for IgG-, IgM-, and IgA-secreting cells, respectively. Proliferation of memBcs correlates inversely to immunoglobulin-secreting capacity, suggesting compensatory hyperproliferation. Furthermore, patients with no serum IgA can still have a detectable IgA ELISpot assay result in vitro. Most importantly, the large heterogeneity of memBc function in patients with CVID homogenously grouped by means of fluorescence-activated cell sorting allowed additional subclassification based on memBc/plasmablast function.
CONCLUSION: These data suggest almost normal memBc/immunoglobulin-secreting plasmablast functionality in some patients if sufficient stimulatory signals are delivered, which might open up opportunities for new therapeutic approaches.
OBJECTIVE: We established and validated a memBc enzyme-linked immunosorbent spot (ELISpot) assay that reveals the capacity of memBcs to develop into antibody-secreting cells and present an idea for a new classification based on this functional capacity.
METHODS: The memBc ELISpot assay, combined with flow cytometry, was applied to patients with confirmed CVID in comparison with age-matched healthy control subjects.
RESULTS: Ex vivo frequency of IgG-, IgM-, and IgA-secreting plasmablasts was significantly diminished by 27.2-, 2.4-, and 23.3-fold, respectively, compared with that seen in healthy control subjects. Moreover, in vitro differentiation of memBcs into antibody-secreting cells was 6.1-, 2.6-, and 3.7-fold significantly reduced for IgG-, IgM-, and IgA-secreting cells, respectively. Proliferation of memBcs correlates inversely to immunoglobulin-secreting capacity, suggesting compensatory hyperproliferation. Furthermore, patients with no serum IgA can still have a detectable IgA ELISpot assay result in vitro. Most importantly, the large heterogeneity of memBc function in patients with CVID homogenously grouped by means of fluorescence-activated cell sorting allowed additional subclassification based on memBc/plasmablast function.
CONCLUSION: These data suggest almost normal memBc/immunoglobulin-secreting plasmablast functionality in some patients if sufficient stimulatory signals are delivered, which might open up opportunities for new therapeutic approaches.