Altered dendritic cell function in response to sera of common variable immunodeficiency patients

Nourizadeh, Maryam; Aghamohammadi, Asghar; Moazzeni, Seyed Mohammad; Mahdavi, Mehdi; Jalili, Ahmad; Rezaei, Nima; Hadjati, Jamshid

doi:10.1007/s00011-007-7081-7

Cited by 9 publications

(4 citation statements)

References 33 publications

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“…Thus, the observed T and B cell defects in CVID patients could be secondary to a functional DC defect. Several studies have suggested deficient maturation and function of DCs in CVID, but the functional studies have been performed mainly on monocyte‐derived DCs (moDC) , possibly representing the in‐vitro correlate to the inflammatory DC . Inflammatory DCs and the so‐called naturally occurring DCs have different haematopoietic ancestors and functions , making it necessary to study these cell types separately.…”

Section: Introductionmentioning

confidence: 99%

“…Numerous reports have demonstrated low numbers of naturally occurring DCs in the peripheral blood of CVID patients , and impaired production of IFN‐α by pDCs upon TLR‐9 activation has been suggested . However, although a number of papers implicate DC in the primary pathogenesis of CVID , it is still unclear if DC functionality is deficient at the single cell level. Furthermore, a potential underlying deficiency in bone marrow production, resulting in selectively low DC numbers in peripheral blood, has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

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Common variable immunodeficiency revisited: normal generation of naturally occurring dendritic cells that respond to Toll-like receptors 7 and 9

Taraldsrud

Fevang

Aukrust

et al. 2014

Clinical and Experimental Immunology

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SummaryPatients with common variable immunodeficiency (CVID) have reduced numbers and frequencies of dendritic cells (DCs) in blood, and there is also evidence for defective activation through Toll-like receptors (TLRs). Collectively, these observations may point to a primary defect in the generation of functional DCs. Here, we measured frequencies of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) in peripheral blood of 26 CVID patients and 16 healthy controls. The results show that the patients have reduced absolute counts of both subsets. However, the decreased numbers in peripheral blood were not reflected in reduced frequencies of CD34 + pDC progenitors in the bone marrow. Moreover, studies at the single cell level showed that DCs from CVID patients and healthy controls produced similar amounts of interferon-α or interleukin-12 and expressed similar levels of activation markers in response to human cytomegalovirus and ligands for TLR-7 and TLR-9. The study represents the most thorough functional characterization to date, and the first to assess bone marrow progenitor output, of naturally occurring DCs in CVID. In conclusion, it seems unlikely that CVID is secondary to insufficient production of naturally occurring DCs or a defect in their signalling through TLR-7 or TLR-9.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Common variable immunodeficiency revisited: normal generation of naturally occurring dendritic cells that respond to Toll-like receptors 7 and 9

Taraldsrud

Fevang

Aukrust

et al. 2014

Clinical and Experimental Immunology

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“…CVID has been associated with defective in vitro maturation of DCs from monocytes, at least in a subset of patients [16,17], and with disturbances in the monocyte responses upon LPS stimulation in vitro [18]. Additionally, CVID patients were shown to have reduced numbers of circulating DCs [19,20], with perturbed differentiation and function, namely reduced expression levels of the co‐stimulatory molecules CD86 and CD80, an impaired ability to produce interleukin (IL)‐12 upon stimulation [21–23], as well as lower antigen‐presenting capacity in mixed lymphocyte reactions [22,23].…”

Section: Introductionmentioning

confidence: 99%

Monocyte activation is a feature of common variable immunodeficiency irrespective of plasma lipopolysaccharide levels

Barbosa

Silva

Tendeiro

et al. 2012

Clinical and Experimental Immunology

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“…The allele and genotype frequencies of IL-12 at position –1188 were similar in patients and controls. In a study on dendritic cells cultured in the presence of CVID patient sera, there was no significant difference in the production of IL-12 between patients and controls [42]. …”

Section: Discussionmentioning

confidence: 99%

Cytokine Gene Polymorphisms in Common Variable Immunodeficiency

Rezaei

Aghamohammadi

Shakiba

et al. 2009

Int Arch Allergy Immunol

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Common variable immunodeficiency (CVID) is a heterogeneous group of disorders, characterized by hypogammaglobulinemia and an increased susceptibility to recurrent infections, autoimmunity and cancers. There are some conflicting results regarding the cytokine profile of CVID patients. While cytokine production could be associated with gene polymorphism, genetic profiles of a number of cytokines were analyzed in this study. The allele and genotype frequencies of the polymorphic genes coding for interleukin (IL)-2, IL-12, interferon-γ and transforming growth factor (TGF)-β were investigated in 30 patients with CVID in comparison with 140 controls. The genotype TGF-β CG at position +915 was significantly overrepresented in the patient group, while the frequencies of the genotypes TGF-β TT at +869 and GG at +915 were significantly decreased in the patient group in comparison with controls. TGF-β TC and IL-2 GT were the most frequent haplotypes in the patients, whereas the TGF-β TG haplotype was significantly decreased in the patient group. The allele and genotype frequencies of interferon-γ at position UTR +5644 and also IL-12 at position –1188 were similar in patients and controls. Cytokine single nucleotide polymorphisms could play a role in the pathophysiology of CVID. Considering the significantly lower frequency of the high production haplotype (TG) and the higher frequency of the low production halplotype (TC) of TGF-β, low production of this cytokine is expected in some CVID patients.

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Altered dendritic cell function in response to sera of common variable immunodeficiency patients

Cited by 9 publications

References 33 publications

Common variable immunodeficiency revisited: normal generation of naturally occurring dendritic cells that respond to Toll-like receptors 7 and 9

Common variable immunodeficiency revisited: normal generation of naturally occurring dendritic cells that respond to Toll-like receptors 7 and 9

Monocyte activation is a feature of common variable immunodeficiency irrespective of plasma lipopolysaccharide levels

Cytokine Gene Polymorphisms in Common Variable Immunodeficiency

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