Recurrent respiratory tract infections (RRTI) in the elderly: from phenotypic and immunological characterizaton to a mechanistic unravelling of a potential primary immunodeficiency (PID).

Recurrent respiratory tract infections (RRTI) in the elderly: from phenotypic and immunological characterizaton to a mechanistic unravelling of a potential primary immunodeficiency (PID). - Recurrent respiratory tract infections (RRTI) in the elderly.

Status

Active, not recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON42241

Enrollment

Registered

2015-05-04

Start date

2015-05-21

Completion date

Unknown

Last updated

2024-08-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

humoral deficiency

Interventions

None listed

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: - > 45 years old AND - two or more documented invasive bacterial or viral sino-, and/or pulmonary infections over the previous year - no RRTI in early adulthood, adolescence or childhood AND/OR - an atypical microbial aetiology, an atypical course of infection or a belated response or early relapse on antibiotic treatments

Exclusion criteria

Exclusion criteria: - secundary immunodeficiency (for example HIV, immunesuppresiva, malignancy)

Design outcomes

Primary

Measure	Time frame
Innate Immunity 1. integrity of the NADPH-oxidase pathway in granulocytes using the DHR123 assay. 2. cytokine production (IL-1β, IL-10, IL-12p40, IL-18, TNF, IFN-a, IFN-γ and IFN-β) in whole blood stimulated with TLR ligands (+/- IFN-γ) using Bioplex assays (Luminex). 3. complement activation (classical, alternative and MBL pathways) by Sandwich Elisa. Analyses of B cell subsets and function: 1. baseline gammaglobulin levels and subgroup analysis. 2. total number and percentages of total B cells (CD19+), naïve B cells (IgG-IgA-/CD27-), IgMmemory B cells (IgG-IgA-/CD27+), switch memory B cells (IgG+IgA+CCD27+), transitional B cells (CD21+) and B1a cells (IgM+CD20+CD27+CD43+CD5+/-) by 16-color FACS on PBMCs. NB: depending on abberant B cell subset: a. gene-expression in subset of B cells using microarray techniques. b. Somatic Hypermutation in B cells with the IGH somatic hypermutation assay. c. surface expression of receptors for BAFF and APRIL (BAFF-R, BCMA, TACI), B7/PD-L1 and CD40 on B cells using flowcytometry, and B cell proliferation after stimulation with BAFF and anti-human IgM. d. antibody responses after stimulation of B cells with pneumococci of serotypes 3 and 4 with and without covalent binding to C3, in the presence of CD40L and IL-10 by ELISA. 3. quantity of KREC*s using real-time qPCR. 4. antibody responses to PnPs antigens after vaccination with 23-valent Pneumovax by multiplexed bead assay (Luminex), one month and one year after vaccination. 5. antibody responses to vaccination with conjugated Prevenar (subsequent to Pneumovax23). Analyses of T cell subsets and function: 1. numbers of various lymphocyte subsets, such as: naïve CD4+/CD8+ T cells (CD45RA+), memory CD4+/CD8+ T cells (CD45RO+), and effector T cells (CD8+CD28-). Within the CD4+ population: Th1, Th2, Th17, FOXP3+T-regs (CD4+CD25+), by 16-color FACS. 2. T-cell proliferation in response to PHA, PMA/ionomycin, high dose anti-CD3 and	—

Measure

Time frame

Innate Immunity 1. integrity of the NADPH-oxidase pathway in granulocytes using the DHR123 assay. 2. cytokine production (IL-1β, IL-10, IL-12p40, IL-18, TNF, IFN-a, IFN-γ and IFN-β) in whole blood stimulated with TLR ligands (+/- IFN-γ) using Bioplex assays (Luminex). 3. complement activation (classical, alternative and MBL pathways) by Sandwich Elisa. Analyses of B cell subsets and function: 1. baseline gammaglobulin levels and subgroup analysis. 2. total number and percentages of total B cells (CD19+), naïve B cells (IgG-IgA-/CD27-), IgMmemory B cells (IgG-IgA-/CD27+), switch memory B cells (IgG+IgA+CCD27+), transitional B cells (CD21+) and B1a cells (IgM+CD20+CD27+CD43+CD5+/-) by 16-color FACS on PBMCs. NB: depending on abberant B cell subset: a. gene-expression in subset of B cells using microarray techniques. b. Somatic Hypermutation in B cells with the IGH somatic hypermutation assay. c. surface expression of receptors for BAFF and APRIL (BAFF-R, BCMA, TACI), B7/PD-L1 and CD40 on B cells using flowcytometry, and B cell proliferation after stimulation with BAFF and anti-human IgM. d. antibody responses after stimulation of B cells with pneumococci of serotypes 3 and 4 with and without covalent binding to C3, in the presence of CD40L and IL-10 by ELISA. 3. quantity of KREC*s using real-time qPCR. 4. antibody responses to PnPs antigens after vaccination with 23-valent Pneumovax by multiplexed bead assay (Luminex), one month and one year after vaccination. 5. antibody responses to vaccination with conjugated Prevenar (subsequent to Pneumovax23). Analyses of T cell subsets and function: 1. numbers of various lymphocyte subsets, such as: naïve CD4+/CD8+ T cells (CD45RA+), memory CD4+/CD8+ T cells (CD45RO+), and effector T cells (CD8+CD28-). Within the CD4+ population: Th1, Th2, Th17, FOXP3+T-regs (CD4+CD25+), by 16-color FACS. 2. T-cell proliferation in response to PHA, PMA/ionomycin, high dose anti-CD3 and

—

Secondary

Measure	Time frame
nvt	—

Countries

Netherlands

Outcome results