The Functional Role of IgA in the IgM/IgA-Enriched Immunoglobulin Preparation Trimodulin

Bohländer, Fabian; Weißmüller, Sabrina; Riehl, Dennis; Gutscher, Marcus; Schüttrumpf, Jörg; Faust, Stefanie

doi:10.3390/biomedicines9121828

Cited by 7 publications

(17 citation statements)

References 114 publications

(204 reference statements)

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“…Apart from the stronger immune activation by IgA-FcαRI ITAM-signaling, IgA can also mediate stronger immunomodulation via inhibitory ITAMi pathway compared and counteracting to IgG. Which was demonstrated using a neutrophil cell-line ( 123 , 124 ). These immunomodulatory properties have a great therapeutic potential in the treatment of inflammatory diseases ( 95 , 105 ).…”

Section: Iga As Therapeutic Antibodymentioning

confidence: 93%

“…However, as pure IgM and IgA controls were lacking in these studies, some effects could also be attributed to IgA. Recent data confirm that IgA can have important effector functions in such IgM/A-enriched immunoglobulin preparations ( 123 ).…”

Section: Iga As Therapeutic Antibodymentioning

confidence: 96%

“…The opsonization and clearance of causal pathogens was shown by a large repertoire of antigen binding activities, as IgM, IgA and IgG antibody titers against relevant bacteria, viruses and fungi were present in trimodulin. It was shown that the antibodies of trimodulin can opsonize and enhance phagocytosis in vitro ( 123 , 191 ). The trimodulin mediated phagocytosis and inflammatory activation of neutrophils was shown to be dependent on IgA-FcαRI and IgG-FcγR binding, highlighting the anti-pathogenic effects of IgA in this therapeutic antibody preparation ( 123 ).…”

Section: Iga As Therapeutic Antibodymentioning

confidence: 99%

“…It was shown that the antibodies of trimodulin can opsonize and enhance phagocytosis in vitro ( 123 , 191 ). The trimodulin mediated phagocytosis and inflammatory activation of neutrophils was shown to be dependent on IgA-FcαRI and IgG-FcγR binding, highlighting the anti-pathogenic effects of IgA in this therapeutic antibody preparation ( 123 ).…”

Section: Iga As Therapeutic Antibodymentioning

confidence: 99%

“…The immunomodulatory properties of trimodulin on the release of several cytokines and chemokines (e.g. TNF-α, IL-17a, IFN-γ, MCP-1, IL-8, IL-1ra and IL-10) were assessed in different cell-culture models and shown to be significantly stronger compared to IVIg ( 123 , 124 , 194 ). In a neutrophil-cell model, the endotoxin-induced IL-8 release was reduced via binding of the trimodulin IgA-component to FcαRI and subsequent ITAMi signaling ( 123 ).…”

Section: Iga As Therapeutic Antibodymentioning

confidence: 99%

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A new hope? Possibilities of therapeutic IgA antibodies in the treatment of inflammatory lung diseases

Bohländer

2023

Front. Immunol.

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Inflammatory lung diseases represent a persistent burden for patients and the global healthcare system. The combination of high morbidity, (partially) high mortality and limited innovations in the last decades, have resulted in a great demand for new therapeutics. Are therapeutic IgA antibodies possibly a new hope in the treatment of inflammatory lung diseases? Current research increasingly unravels the elementary functions of IgA as protector against infections and as modulator of overwhelming inflammation. With a focus on IgA, this review describes the pathological alterations in mucosal immunity and how they contribute to chronic inflammation in the most common inflammatory lung diseases. The current knowledge of IgA functions in the circulation, and particularly in the respiratory mucosa, are summarized. The interplay between neutrophils and IgA seems to be key in control of inflammation. In addition, the hurdles and benefits of therapeutic IgA antibodies, as well as the currently known clinically used IgA preparations are described. The data highlighted here, together with upcoming research strategies aiming at circumventing the current pitfalls in IgA research may pave the way for this promising antibody class in the application of inflammatory lung diseases.

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Section: Iga As Therapeutic Antibodymentioning

confidence: 93%

Section: Iga As Therapeutic Antibodymentioning

confidence: 96%

Section: Iga As Therapeutic Antibodymentioning

confidence: 99%

Section: Iga As Therapeutic Antibodymentioning

confidence: 99%

Section: Iga As Therapeutic Antibodymentioning

confidence: 99%

See 3 more Smart Citations

A new hope? Possibilities of therapeutic IgA antibodies in the treatment of inflammatory lung diseases

Bohländer

2023

Front. Immunol.

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Comparison of Crude and Wine-Steamed Corni Fructus Based on UPLC-Q-TOF-MS Combined With Pharmacodynamics Screening

Jia,

Lv,

Yang

et al. 2023

Natural Product Communications

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Introduction: The dry ripe sarcocarp of Cornus officinalis Sieb.et Zucc (in Chinese Shanyurou) has the properties of tonifying the liver and kidney. Wine-steamed Corni Fructus, as the main processed product from Corni Fructus, is widely used in traditional Chinese clinical medicine. This article aims to study the Corni Fructus composition changes when wine-steamed processed and to discuss the optimal processing technology of Corni Fructus combined with pharmacological experiments. Methods: The differences between Corni Fructus and wine-steamed Corni fructus constituents were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. The effects of Corni Fructus and wine-steamed Corni Fructus with different processing times were studied from the aspects of immune activity, liver protection, and kidney yin deficiency. Results: A total of 132 compounds were identified in the wine-steamed process of Corni Fructus. There were no significant differences in immune function, liver protection, and kidney yin deficiency of Corni Fructus with different processing times. However, the effects of Corni Fructus processed by wine-steaming were significantly enhanced in all aspects. Conclusion: The wine-steamed Corni Fructus chemical composition may be the material basis for enhancing liver and kidney function. After processing, Corni Fructus can enhance immune function, liver protection function, and liver and kidney toning function.

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The immunomodulating activity of trimodulin (polyvalent IgM, IgA, IgG solution): a post hoc analysis of the phase II CIGMA trial

Singer,

Torres,

Heinz

et al. 2023

Crit Care

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Background The phase II CIGMA trial performed in 160 patients with severe community-acquired pneumonia (sCAP) found treatment with trimodulin (human polyvalent immunoglobulin [Ig]: ~ 23% IgM, ~ 21% IgA, ~ 56% IgG) was associated with a lower mortality in those patients with elevated baseline serum levels of C-reactive protein (CRP) and/or subnormal IgM. Methods In this post hoc analysis, the pharmacodynamic effects of trimodulin treatment (182.6 mg/kg/day for 5 days) were investigated on Ig replenishment, cellular markers of inflammation (absolute neutrophil [ANC] and lymphocyte [ALC] count, neutrophil-to-lymphocyte ratio [NLR]), and soluble markers of inflammation (procalcitonin [PCT] and CRP). The impact of these pharmacodynamic effects on mortality was also evaluated. Results Compared with healthy subjects, baseline serum levels of IgM, IgG, and ALC were significantly lower, and ANC, NLR, PCT and CRP significantly higher in sCAP patients (p < 0.0001). Low Ig concentrations increased with trimodulin. Normalization of ANC (analysis of variance [ANOVA] p = 0.016) and PCT (ANOVA p = 0.027) was more rapid with trimodulin compared with placebo. These and other effects were more evident in patients with low baseline IgM levels. Normalization of PCT and CRP levels was both steadier and faster with trimodulin treatment. In patients with low baseline ALC, trimodulin was associated with a lower 28-day all-cause mortality rate (14.5% vs 32.1% in placebo, p = 0.043) and more ventilator-free days ([VFD]; median VFD: 3.5 vs 11 in placebo, p = 0.043). These numerical differences were greater if baseline IgM was also low (low ALC, low IgM: 8.1% mortality vs 34.1% placebo, p = 0.006; 3 VFD vs 15 VFD, p = 0.009, respectively). Results were consistent in patients with high baseline CRP (low ALC, high CRP: 10.9% mortality vs 34.1% placebo, p = 0.011). Conclusions This post hoc pharmacodynamic analysis of a blinded phase II trial suggests that trimodulin compensates for, and more rapidly modifies, the dysregulated inflammatory response seen in sCAP patients. Trimodulin was associated with significantly lower mortality and more VFD in subgroups with high CRP and low ALC. This effect was particularly marked in patients who also had low baseline IgM values. These findings require confirmation in prospective trials.

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The Functional Role of IgA in the IgM/IgA-Enriched Immunoglobulin Preparation Trimodulin

Cited by 7 publications

References 114 publications

A new hope? Possibilities of therapeutic IgA antibodies in the treatment of inflammatory lung diseases

A new hope? Possibilities of therapeutic IgA antibodies in the treatment of inflammatory lung diseases

Comparison of Crude and Wine-Steamed Corni Fructus Based on UPLC-Q-TOF-MS Combined With Pharmacodynamics Screening

The immunomodulating activity of trimodulin (polyvalent IgM, IgA, IgG solution): a post hoc analysis of the phase II CIGMA trial

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