The Unexplored Roles of Human Serum IgA

Leong, Ka Wai; Ding, Jeak Ling

doi:10.1089/dna.2014.2639

Cited by 93 publications

(81 citation statements)

References 65 publications

(73 reference statements)

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“…Another explanation for the increase of IgA levels conceivably lies in a shifted balance of IgA production and degradation that arises during aging, implied by the increase of IgA nephropathy (the deposition of IgA antibody in the glomeruli of kidneys) with age48. Apart from reinforcing immune responses during infections, IgA under normal conditions has a role as an anti-inflammatory antibody that maintains homeostasis4950; hence high IgA levels in elderly do not necessarily signify a higher level of protection against infections. More research on the role of serum IgA in the protection against B. pertussis is entailed.…”

Section: Discussionmentioning

confidence: 99%

Impact of age and vaccination history on long-term serological responses after symptomatic B. pertussis infection, a high dimensional data analysis

Twillert

Marinović

Kuipers

et al. 2017

Sci Rep

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Capturing the complexity and waning patterns of co-occurring immunoglobulin (Ig) responses after clinical B. pertussis infection may help understand how the human host gradually loses protection against whooping cough. We applied bi-exponential modelling to characterise and compare B. pertussis specific serological dynamics in a comprehensive database of IgG, IgG subclass and IgA responses to Ptx, FHA, Prn, Fim2/3 and OMV antigens of (ex-) symptomatic pertussis cases across all age groups. The decay model revealed that antigen type and age group were major factors determining differences in levels and kinetics of Ig (sub) classes. IgG-Ptx waned fastest in all age groups, while IgA to Ptx, FHA, Prn and Fim2/3 decreased fast in the younger but remained high in older (ex-) cases, indicating an age-effect. While IgG1 was the main IgG subclass in response to most antigens, IgG2 and IgG3 dominated the anti-OMV response. Moreover, vaccination history plays an important role in post-infection Ig responses, demonstrated by low responsiveness to Fim2/3 in unvaccinated elderly and by elevated IgG4 responses to multiple antigens only in children primed with acellular pertussis vaccine (aP). This work highlights the complexity of the immune response to this re-emerging pathogen and factors determining its Ig quantity and quality.

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Section: Discussionmentioning

confidence: 99%

Impact of age and vaccination history on long-term serological responses after symptomatic B. pertussis infection, a high dimensional data analysis

Twillert

Marinović

Kuipers

et al. 2017

Sci Rep

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“…The additional antiinflammatory roles of secretory IgA have been extensively reviewed by others [11,12]. Serum IgA is a monomeric molecule, which has either anti-or pro-inflammatory roles depending on the circumstances [13,14]. During homoeostasis, serum IgA is hypothesized to bind FcaRI and to induce inhibitory signalling, thereby downregulating cell activation [15].…”

Section: Iga and Fcarimentioning

confidence: 99%

Immunoglobulin A: magic bullet or Trojan horse?

Heineke

Egmond

2017

Eur J Clin Investigation

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Background Neutrophils participate in the first line of defense by executing several killing mechanisms, including phagocytosis, degranulation and the release of neutrophil extracellular traps. Additionally, they can orchestrate the adaptive immune system by secreting cytokines and chemokines. Opsonization with antibodies aids in the recognition of pathogens, via binding to Fc receptors on the neutrophil surface. Immunoglobulin A (IgA) is the most abundant antibody at mucosal sites and has multiple functions in homeostasis and immunity. Neutrophils and IgA can interact via the IgA Fc receptor FcRI (CD89), leading to pro-or anti-inflammatory responses.

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“…Both mucosal and serum IgA can have either proinflammatory or anti-inflammatory effects in vitro although the function of serum IgA has not yet been fully defined 4 . These effects are in part mediated by binding of IgA to the immunoglobulin Fc-α receptor (also known as CD89) on cells of the innate immune system; mIgA binding to CD89 typically has anti-inflammatory effects, whereas pIgA binding to CD89 is proinflammatory 5 .…”

mentioning

confidence: 99%

The mucosa–kidney axis in IgA nephropathy

2015

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Links between IgA nephropathy (IgAN) and the mucosa have been recognized since the 1970s. In particular, the observation of visible haematuria induced by respiratory infections in patients with IgAN and the association of IgAN with diseases in which the mucosa plays a part, especially coeliac disease, have been taken as evidence of a mucosa-kidney axis. Here, we review current evidence that links the mucosa, in particular the gastrointestinal mucosa, and IgA produced by the bone marrow with IgAN. Genome-wide association studies in patients with IgAN have identified risk loci in genes involved in the intestinal mucosal integrity and immune network. Furthermore, the systemic immune response to mucosal antigens in IgAN is increased. Moreover, patients with IgAN have an increased reactivity to dietary proteins associated with subclinical intestinal mucosal inflammation. Associations between IgAN and gastrointestinal diseases have also been reported in a small number of patients, but whether these diseases share a common pathogenesis or whether gastrointestinal inflammation exacerbates IgAN is uncertain. Indeed, mucosal alterations such as infections could activate the innate immune system, aggravate a pre-existing IgAN and promote disease manifestations such as macrohaematuria. Various clinical interventions and trials targeting the mucosa or presumed mucosa-associated mechanisms have so far not yielded consistent findings and the results of ongoing trials are eagerly awaited.

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The Unexplored Roles of Human Serum IgA

Cited by 93 publications

References 65 publications

Impact of age and vaccination history on long-term serological responses after symptomatic B. pertussis infection, a high dimensional data analysis

Impact of age and vaccination history on long-term serological responses after symptomatic B. pertussis infection, a high dimensional data analysis

Immunoglobulin A: magic bullet or Trojan horse?

The mucosa–kidney axis in IgA nephropathy

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