IgA and FcαRI: Versatile Players in Homeostasis, Infection, and Autoimmunity

Gool, Melissa Maria Johanna van; Egmond, Marjolein van

doi:10.2147/itt.s266242

Cited by 37 publications

(44 citation statements)

References 257 publications

(240 reference statements)

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“…In humans, FcaRI is expressed on immune cells such as eosinophils, neutrophils and monocytes but not on mast cells. Serum IgA in humans is supposed to negatively regulate immune cell activation and degranulation via FcaRI (27,28). One could hypothesize that lower IgA in CSU would lead to increased activation of eosinophils, neutrophils and monocytes resulting in inflammation and autoimmunity.…”

Section: Discussionmentioning

confidence: 99%

Lower IgA Levels in Chronic Spontaneous Urticaria Are Associated With Lower IgE Levels and Autoimmunity

et al. 2021

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BackgroundThe pathogenesis of chronic spontaneous urticaria (CSU) is still insufficiently understood. Recent findings suggest that immunoglobulins, in particular IgE but also IgA, play a role in the development of CSU.ObjectiveOur aim was to assess differences in clinical and laboratory markers between CSU patients with and without lower levels of serum IgA and IgE.MethodsWe analyzed the data of 606 patients with CSU by dividing them into four groups based on their IgA and IgE levels. The groups were compared for their spectrum of symptoms, disease activity, concomitant autoimmunity and routine laboratory markers. Autoreactivity was assessed by basophil activation test (BAT). Moreover, IgE-anti-thyroid peroxidase (TPO) was measured.ResultsOf the patients with lower IgE levels, 66.5% also had lower IgA levels (r=0.316, p<0.001). Patients with lower IgA and lower IgE levels showed a higher prevalence of recurrent angioedema (p=0.03, p=0.04) and concomitant autoimmunity (p=0.006, p<0.001). Autoreactivity was also found more frequently in patients with lower IgA and lower IgE levels (p=0.003, p<0.001). Reduced basophil counts were linked to both, lower IgA and lower IgE levels (p<0.001), whereas low eosinophil counts were primarily present in patients with lower IgE levels (p=0.04, p<0.001). Patients with elevated IgE-anti-TPO levels had lower IgA (p=0.007) and IgE levels (p=0.001).ConclusionLower IgA levels in CSU are linked to lower IgE levels and features of autoimmune urticaria. Our findings encourage to screen CSU patients for serum IgA and IgE levels and to further assess their role as disease biomarkers.

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Section: Discussionmentioning

confidence: 99%

Lower IgA Levels in Chronic Spontaneous Urticaria Are Associated With Lower IgE Levels and Autoimmunity

et al. 2021

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“…IgA that is enriched in the respiratory system and intestinal tract is named mucosal IgA, as it participates in host-pathogen defense in the mucosal lumen. Mucosal IgA is dimeric IgA (linked by J chain) while circulating serum IgA is monomeric ( 98 ). Serum IgA elevation is reported in severe PH associated with primary Sjögren's syndrome ( 73 ), and IgA-producing plasma cells are found in the blood of patients with IPAH ( 51 ).…”

Section: Auto-antibodies Productionmentioning

confidence: 99%

Autoimmunity in Pulmonary Arterial Hypertension: Evidence for Local Immunoglobulin Production

Shu

Xing

Wang

2021

Front. Cardiovasc. Med.

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Pulmonary arterial hypertension (PAH) is a progressive life-threatening disease. The notion that autoimmunity is associated with PAH is widely recognized by the observations that patients with connective tissue diseases or virus infections are more susceptible to PAH. However, growing evidence supports that the patients with idiopathic PAH (IPAH) with no autoimmune diseases also have auto-antibodies. Anti-inflammatory therapy shows less help in decreasing auto-antibodies, therefore, elucidating the process of immunoglobulin production is in great need. Maladaptive immune response in lung tissues is considered implicating in the local auto-antibodies production in patients with IPAH. In this review, we will discuss the specific cell types involved in the lung in situ immune response, the potential auto-antigens, and the contribution of local immunoglobulin production in PAH development, providing a theoretical basis for drug development and precise treatment in patients with PAH.

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“…ITAMi-maintained immune homeostatic conditions by counteracting ITAM induced effector outcomes, like reduced reactive oxygen species (ROS) or inflammatory cytokine release ( 44 , 45 ). Further, immune modulation via monovalent targeting of IgA–Fc α RI-axis is known for several in vitro and in vivo models ( 31 , 45 , 106 – 108 ). Here we show for the first time immune modulation by IgA and IgM enriched immunoglobulin trimodulin via ITAMi signaling.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulation: Immunoglobulin Preparations Suppress Hyperinflammation in a COVID-19 Model via FcγRIIA and FcαRI

et al. 2021

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The rapid spread of SARS-CoV-2 has induced a global pandemic. Severe forms of COVID-19 are characterized by dysregulated immune response and “cytokine storm”. The role of IgG and IgM antibodies in COVID-19 pathology is reasonably well studied, whereas IgA is neglected. To improve clinical outcome of patients, immune modulatory drugs appear to be beneficial. Such drugs include intravenous immunoglobulin preparations, which were successfully tested in severe COVID-19 patients. Here we established a versatile in vitro model to study inflammatory as well as anti-inflammatory processes by therapeutic human immunoglobulins. We dissect the inflammatory activation on neutrophil-like HL60 cells, using an immune complex consisting of latex beads coated with spike protein of SARS-CoV-2 and opsonized with specific immunoglobulins from convalescent plasma. Our data clarifies the role of Fc-receptor-dependent phagocytosis via IgA-FcαRI and IgG-FcγR for COVID-19 disease followed by cytokine release. We show that COVID-19 associated inflammation could be reduced by addition of human immunoglobulin preparations (IVIG and trimodulin), while trimodulin elicits stronger immune modulation by more powerful ITAMi signaling. Besides IgG, the IgA component of trimodulin in particular, is of functional relevance for immune modulation in this assay setup, highlighting the need to study IgA mediated immune response.

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IgA and FcαRI: Versatile Players in Homeostasis, Infection, and Autoimmunity

Cited by 37 publications

References 257 publications

Lower IgA Levels in Chronic Spontaneous Urticaria Are Associated With Lower IgE Levels and Autoimmunity

Lower IgA Levels in Chronic Spontaneous Urticaria Are Associated With Lower IgE Levels and Autoimmunity

Autoimmunity in Pulmonary Arterial Hypertension: Evidence for Local Immunoglobulin Production

Immunomodulation: Immunoglobulin Preparations Suppress Hyperinflammation in a COVID-19 Model via FcγRIIA and FcαRI

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