IL-10 and IL-4 co-operate to normalize<i>in vitro</i>IgA production in IgA-deficient (IgAD) patients

Marconi, Massimo; Plebani, Alessandro; Avanzini, Maria Antonietta; Maccario, Rita; Pistorio, Angela; Duse, Marzia; Stringa, M; Monafò, V.

doi:10.1046/j.1365-2249.1998.00589.x

Cited by 41 publications

(41 citation statements)

References 27 publications

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“…Patients with IgA deficiency are usually defined by serum IgA levels of Ͻ0.05 g/liter (normal levels are 0.5 to 3.5 g/liter), but many, if not most, IgA-deficient patients have low but detectable levels of serum IgA antibodies (9,30) and can produce IgA antibodies at near-normal levels in vitro (8,23). This is in contrast to the complete lack of IgA production in IgA-deficient mice, which lack crucial gene segments for expressing IgA heavy chains (17).…”

Section: Discussionmentioning

confidence: 99%

Central Importance of Immunoglobulin A in Host Defense againstGiardiaspp

Housley²,

et al. 2002

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The protozoan pathogen Giardia is an important cause of parasitic diarrheal disease worldwide. It colonizes the lumen of the small intestine, suggesting that effective host defenses must act luminally. Immunoglobulin A (IgA) antibodies are presumed to be important for controlling Giardia infection, but direct evidence for this function is lacking. B-cell-independent effector mechanisms also exist and may be equally important for antigiardial host defense. To determine the importance of the immunoglobulin isotypes that are transported into the intestinal lumen, IgA and IgM, for antigiardial host defense, we infected gene-targeted mice lacking IgA-expressing B-cells, IgM-secreting B-cells, or all B-cells as controls with Giardia muris or Giardia lamblia GS/M-83-H7. We found that IgA-deficient mice could not eradicate either G. muris or G. lamblia infection, demonstrating that IgA is required for their clearance. Furthermore, although neither B-cell-deficient nor IgA-deficient mice could clear G. muris infections, IgA-deficient mice controlled infection significantly better than B-cell-deficient mice, suggesting the existence of B-cell-dependent but IgA-independent antigiardial defenses. In contrast, mice deficient for secreted IgM antibodies cleared G. muris infection normally, indicating that they have no unique functions in antigiardial host defense. These data, together with the finding that B-cell-deficient mice have some, albeit limited, residual capacity to control G. muris infection, show that IgA-dependent host defenses are central for eradicating Giardia spp. Moreover, B-cell-dependent but IgAindependent and B-cell-independent antigiardial host defenses exist but are less important for controlling infection.

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Section: Discussionmentioning

confidence: 99%

Central Importance of Immunoglobulin A in Host Defense againstGiardiaspp

Housley²,

et al. 2002

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“…[5][6][7] Several authors have demonstrated that B cells from IgAdeficient subjects and CVID patients undergo class-switch recombination (CSR) when stimulated through CD40 (TNFRSF5) together with interleukin-4 (IL-4) or interleukin-10 (IL-10), leading to reconstitution of IgG and IgA production ex vivo. [8][9][10][11][12] However, these effects have not yet been established in vivo and it remains to be seen whether targeting of the CD40 molecule and stimulation with IL-4 and IL-10 are tolerated and therapeutically effective in humans. 13,14 Immunomodulatory intervention with low doses of IL-2 has shown promise in vivo, despite insufficient evidence and proof of safety to support its routine use.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-21 restores immunoglobulin production ex vivo in patients with common variable immunodeficiency and selective IgA deficiency

Borte

Pan‐Hammarström

Liu

et al. 2009

Blood

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“…The clinical picture of SIgAD may vary from absence of clinical manifestations to fully symptomatic form (16). A variety of pathologic mechanisms of SIgAD have been postulated, which include the occurrence of IgA-specific T suppressor cells, inadequate T helper (Th) cell function, an intrinsic B-cell defects (17), or decreased expression of CD40 on monocytes (18). In most cases, the molecular defect is unknown, although in some patients with SIgAD, mutations in TACI gene have been identified (11,12).…”

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The B-cell Compartment in the Peripheral Blood of Children With Different Types of Primary Humoral Immunodeficiency

et al. 2009

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ABSTRACT:The aim of this study was to evaluate the B-cell compartment in the peripheral blood of children with different types of hipogammaglobulinemia: common variable immunodeficiency (CVID), transient hypogammaglobulinemia of infancy (THI), and selective IgA deficiency (SIgAD). We analyzed by flow cytometry the changes in the B-cell subsets with age and showed that children with an early-onset CVID develop similar pattern of B-cell subsets as adult patients with CVID with age, as the levels of memory B cells (CD19 ϩ /CD27 ϩ ) and class-switched memory B cells (, in contrast to age-matched control group, did not increase with age. Children with SIgAD displayed similar changes as patients with CVID only within the class-switched memory B-cell subpopulation. No significant differences in the level of memory B cells and class-switched memory B cells in children with THI in comparison to age-matched control group were observed. There were no differences in the percentage of immature B cells (CD19 ϩ /CD21 low ) among all studied groups. As B-cell subsets in children with THI were normal during entire period of hypogammaglobulinemia, the persistence of low levels of memory B-cell subsets in some children may facilitate the diagnosis of CVID. (5), or primary B-cell defects (6,7) have been reported. In some patients with CVID, defects in B-cell receptors signaling and B cell development have been described, especially mutations in CD19 (8), B-cell activating factor of the tumor necrosis factor family receptor (BAFF-R) (9), inducible costimulator of activated T cells (ICOS) (10), and transmembrane activator and CAML interactor (TACI) (11-14), which are required for maturation of B cells and generation of antibody diversity. Disease is usually diagnosed in the second or third decade of life after a history of recurrent pyogenic sinopulmonary infections (15), but some cases of CVID are diagnosed in the childhood as an early-onset CVID.Selective IgA deficiency (SIgAD) is the most prevalent primary humoral immunodeficiency. The clinical picture of SIgAD may vary from absence of clinical manifestations to fully symptomatic form (16). A variety of pathologic mechanisms of SIgAD have been postulated, which include the occurrence of IgA-specific T suppressor cells, inadequate T helper (Th) cell function, an intrinsic B-cell defects (17), or decreased expression of CD40 on monocytes (18). In most cases, the molecular defect is unknown, although in some patients with SIgAD, mutations in TACI gene have been identified (11,12). SIgAD is considered to be genetically linked with CVID, as the latter may develop from SIgAD (19 -21) and occasionally vice versa (22). Familial studies have implicated the existence of an allelic relationship between SIgAD and CVID, indicating that these disorders have the same molecular defect (23).Transient hypogammaglobulinemia of infancy (THI) is defined by decreased level of IgG (below 2 SD for the agematched healthy children) and in some cases low level of IgA and intact cell-mediated immunity. Prod...

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IL-10 and IL-4 co-operate to normalizein vitroIgA production in IgA-deficient (IgAD) patients

Cited by 41 publications

References 27 publications

Central Importance of Immunoglobulin A in Host Defense againstGiardiaspp

Central Importance of Immunoglobulin A in Host Defense againstGiardiaspp

Interleukin-21 restores immunoglobulin production ex vivo in patients with common variable immunodeficiency and selective IgA deficiency

The B-cell Compartment in the Peripheral Blood of Children With Different Types of Primary Humoral Immunodeficiency

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