The association of IgA deficiency on infection rate, self‐perceived health, and levels of C‐reactive protein in healthy blood donors

Hauge, Sabina Chaudhary; Jensen, Charlotte Kaestel; Nielsen, Leif Kofoed; Pedersen, Ole Birger; Sørensen, Erik; Thørner, Lise Wegner; Hjalgrim, Henrik; Erikstrup, Christian; Nielsen, Kaspar René; Kaspersen, Kathrine Agergård; Didriksen, Maria; Dziegiel, Morten Hanefeld; Ullum, Henrik

doi:10.1111/apm.12807

Cited by 3 publications

(4 citation statements)

References 34 publications

(36 reference statements)

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“…However, SIgM targeted a broader range of microbes and showed less specificity for microbes compared to SIgA (124). Patients can have increased C reactive protein levels, which is indicative for enhanced inflammation, along with an increased risk of death 10–15 years after initial diagnosis (126, 127). In a recent study no risk association was found between IgA deficiency and hospital infections (127).…”

Section: Iga-associated Diseasesmentioning

confidence: 99%

“…Patients can have increased C reactive protein levels, which is indicative for enhanced inflammation, along with an increased risk of death 10–15 years after initial diagnosis (126, 127). In a recent study no risk association was found between IgA deficiency and hospital infections (127). IgA deficiency was also not more common among hospitalized individuals compared to healthy blood donors (123).…”

Section: Iga-associated Diseasesmentioning

confidence: 99%

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IgA and FcαRI: Pathological Roles and Therapeutic Opportunities

2019

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Immunoglobulin A (IgA) is the most abundant antibody class present at mucosal surfaces. The production of IgA exceeds the production of all other antibodies combined, supporting its prominent role in host-pathogen defense. IgA closely interacts with the intestinal microbiota to enhance its diversity, and IgA has a passive protective role via immune exclusion. Additionally, inhibitory ITAMi signaling via the IgA Fc receptor (FcαRI; CD89) by monomeric IgA may play a role in maintaining homeostatic conditions. By contrast, IgA immune complexes (e.g., opsonized pathogens) potently activate immune cells via cross-linking FcαRI, thereby inducing pro-inflammatory responses resulting in elimination of pathogens. The importance of IgA in removal of pathogens is emphasized by the fact that several pathogens developed mechanisms to break down IgA or evade FcαRI-mediated activation of immune cells. Augmented or aberrant presence of IgA immune complexes can result in excessive neutrophil activation, potentially leading to severe tissue damage in multiple inflammatory, or autoimmune diseases. Influencing IgA or FcαRI-mediated functions therefore provides several therapeutic possibilities. On the one hand (passive) IgA vaccination strategies can be developed for protection against infections. Furthermore, IgA monoclonal antibodies that are directed against tumor antigens may be effective as cancer treatment. On the other hand, induction of ITAMi signaling via FcαRI may reduce allergy or inflammation, whereas blocking FcαRI with monoclonal antibodies, or peptides may resolve IgA-induced tissue damage. In this review both (patho)physiological roles as well as therapeutic possibilities of the IgA-FcαRI axis are addressed.

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Section: Iga-associated Diseasesmentioning

confidence: 99%

Section: Iga-associated Diseasesmentioning

confidence: 99%

IgA and FcαRI: Pathological Roles and Therapeutic Opportunities

2019

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“…Consistent with the previously described anti-inflammatory functions of IgA, many IgA-deficient individuals have an increased incidence of autoimmune disease, recurrent mucosal infections, and an increased incidence of allergy, 38 although others do not seem to suffer from any significant negative health effects. 39 Interestingly, despite the lack of IgA, CD89 remains expressed on cells in these individuals. 40 It is therefore thought that in the absence of mIgA interactions with CD89, anti-inflammatory IgA immune modulation does not occur, thus favoring autoimmunity in the majority of IgA-deficient individuals.…”

Section: Fcari (Cd89): a Bifunctional Regulator Of Iga Responsesmentioning

confidence: 98%

The Multifaceted Nature of Immunoglobulin A and Its Complex Role in HIV

López

Shattock

Kent

et al. 2018

AIDS Research and Human Retroviruses

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IgA is the most abundant immunoglobulin in mucosal secretions, and understanding the role of IgA in both protection from HIV acquisition and modulation of HIV disease progression is a field of considerable controversy and renewed research interest. Analysis of the RV144 clinical trial associated plasma HIV envelope-specific monomeric IgA from vaccines with reduced vaccine efficacy. The RV144 trial, however, only assessed for plasma IgA, which was not further subclassed, and the role of mucosal IgA was not addressed as mucosal samples were not collected. On the other hand, several studies have detected envelope-specific IgA in mucosal secretions of highly exposed persistently seronegative cohorts, while recent macaque simian-HIV passive immunization studies have suggested a potentially protective role for mucosal IgA. It is well established that total IgA in serum appears to correlate with HIV disease progression. In contrast, a selective deficit of anti-HIV IgA responses in HIV infection is apparent, with a number of recent studies beginning to elucidate the mechanisms behind these dysfunctional IgA responses. In this review, we highlight the dichotomy that exists in the literature as to whether anti-HIV IgA is protective or harmful to the host. Herein, we emphasize the importance of distinguishing between monomeric, multimeric, and isoforms of IgA and review what is known about the complex and diverse interactions of various molecular forms of IgA with HIV in both the systemic circulation and mucosal compartments.

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“…Dennoch manifestiert sich die Erkrankung bei 50 % der PatientInnen erst im Erwachsenenalter [35]. Auch im Erwachsenenalter sind die häufigsten PID-Antikörpermangelerkrankungen [36]. Tatsächlich gibt es z.…”

Section: Pid Bei Erwachsenenunclassified