Classification of common variable immunodeficiencies using flow cytometry and a memory B-cell functionality assay

Rösel, Amelia L.; Scheibenbogen, Carmen; Schliesser, Ulrike; Sollwedel, André; Hoffmeister, Bodo; Hanitsch, Leif G.; Bernuth, Horst von; Krüger, Renate; Warnatz, Klaus; Volk, Hans‐Dieter; Thomas, Sheila

doi:10.1016/j.jaci.2014.06.022

Cited by 27 publications

(21 citation statements)

References 49 publications

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“…[24][25][26][27]44,45 However, the plethora of immunological abnormalities and their unequal distribution among different cohorts have made it challenging to uniformly identify subgroups in the CVID population.…”

Section: A B C Dmentioning

confidence: 99%

The immunophenotypic fingerprint of patients with primary antibody deficiencies is partially present in their asymptomatic first-degree relatives

et al. 2016

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T he etiology of primary antibody deficiencies is largely unknown. Beside rare monogenic forms, the majority of cases seem to have a more complex genetic basis. Whereas common variable immunodeficiency has been investigated in depth, there are only a few reports on milder primary antibody deficiencies such as idiopathic primary hypogammaglobulinemia and IgG subclass deficiency. We performed flow cytometric immunophenotyping in 33 patients with common variable immunodeficiency, 23 with idiopathic primary hypogammaglobulinemia and 21 with IgG subclass deficiency, as well as in 47 asymptomatic first-degree family members of patients and 101 unrelated healthy controls. All three groups of patients showed decreased memory B-and naïve T-cell subsets and decreased B-cell activating factor receptor expression. In contrast, circulating follicular helper T-cell frequency and expression of inducible T-cell costimulator and chemokine receptors were only significantly altered in patients with common variable immunodeficiency. Asymptomatic firstdegree family members of patients demonstrated similar, albeit intermediate, alterations in naïve and memory B-and T-cell subsets. About 13% of asymptomatic relatives had an abnormal peripheral B-cell composition. Furthermore, asymptomatic relatives showed decreased levels of CD4 + recent thymic emigrants and increased central memory T cells. Serum IgG and IgM levels were also significantly lower in asymptomatic relatives than in healthy controls. We conclude that, in our cohort, the immunophenotypic landscape of primary antibody deficiencies comprises a spectrum, in which some alterations are shared between all primary antibody deficiencies whereas others are only associated with common variable immunodeficiency. Importantly, asymptomatic first-degree family members of patients were found to have an intermediate phenotype for peripheral Band T-cell subsets.

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Section: A B C Dmentioning

confidence: 99%

The immunophenotypic fingerprint of patients with primary antibody deficiencies is partially present in their asymptomatic first-degree relatives

et al. 2016

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“…cluding susceptibility to sinopulmonary infections, granulomatous disease, lymphoproliferation, and autoimmunity (in subsets of patients) (88)(89)(90). Attempts have been made over the past decade or longer to classify CVID patients based on differences in peripheral B cell subsets, and some of these have provided clinical correlations, which may have prognostic value in subgroups of patients (91)(92)(93)(94)(95)(96)(97)(98). B cell subset analysis, in particular evaluation of memory B cells and switched memory B cells, has been incorporated into the newer diagnostic criteria as an accessory criterion (88), as the majority of CVID patients have impaired peripheral B cell differentiation and reduced class-switched memory B cells.…”

Section: Cellular Immunophenotyping In Pidsmentioning

confidence: 99%

Flow Cytometry, a Versatile Tool for Diagnosis and Monitoring of Primary Immunodeficiencies

Abraham

Aubert

2016

Clin Vaccine Immunol

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bGenetic defects of the immune system are referred to as primary immunodeficiencies (PIDs). These immunodeficiencies are clinically and immunologically heterogeneous and, therefore, pose a challenge not only for the clinician but also for the diagnostic immunologist. There are several methodological tools available for evaluation and monitoring of patients with PIDs, and of these tools, flow cytometry has gained prominence, both for phenotyping and functional assays. Flow cytometry allows real-time analysis of cellular composition, cell signaling, and other relevant immunological pathways, providing an accessible tool for rapid diagnostic and prognostic assessment. This minireview provides an overview of the use of flow cytometry in disease-specific diagnosis of PIDs, in addition to other broader applications, which include immune phenotyping and cellular functional measurements.

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“…Rösel et al 46 examined the memory B cell ELISPOT assay in fifteen CVID patients as another tool to characterize antibody response and B cell function and concluded that this test might be useful to help identify patients who might benefit from treatment with B cell stimulating cytokines. Mousalleum and collaborators 47 reported their experience of using whole genome sequencing (WES) to diagnose molecular defects in six patients with unidentified PIDs.…”

Section: Diagnostic Testing Of Primary Immunodeficienciesmentioning

confidence: 99%

Advances in clinical immunology in 2015

Chinen

Notarangelo

Shearer

2016

Journal of Allergy and Clinical Immunology

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Advances in clinical immunology in the past year included the report of practice parameters for the diagnosis and management of primary immune deficiencies (PIDs) to guide the clinician in the approach to these relatively uncommon disorders. We have learned of new gene defects causing immunodeficiency and of new phenotypes expanding the spectrum of conditions caused by mutations found in one gene, such as a specific RTEL1 mutation causing isolated NK cell deficiency, and mutations in RAB27 resulting in immunodeficiency without albinism. Advances in diagnosis included the increasing use of whole exome sequencing to identify gene defects, and the measurement of serum free light chains to identify secondary hypogammaglobulinemias. For several PIDs, improved outcomes have been reported after definitive therapy with hematopoietic stem cell transplantation and gene therapy.

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Classification of common variable immunodeficiencies using flow cytometry and a memory B-cell functionality assay

Cited by 27 publications

References 49 publications

The immunophenotypic fingerprint of patients with primary antibody deficiencies is partially present in their asymptomatic first-degree relatives

The immunophenotypic fingerprint of patients with primary antibody deficiencies is partially present in their asymptomatic first-degree relatives

Flow Cytometry, a Versatile Tool for Diagnosis and Monitoring of Primary Immunodeficiencies

Advances in clinical immunology in 2015

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