The complement cascade in lung injury and disease

Detsika, M. G.; Palamaris, K.; Dimopoulou, I.; Kotanidou, A.; Orfanos, S. E.

doi:10.1186/s12931-023-02657-2

Cited by 7 publications

(1 citation statement)

References 153 publications

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“…Numerous studies have demonstrated the potential effectiveness of the application of monoclonal antibodies that target complement in treating lung diseases [ 68 , 69 ]. The involvement of the complement system in both acute and chronic lung conditions, such as asthma, underscores the opportunity for novel approaches aimed at targeting complement factors to address lung diseases.…”

Section: Discussionmentioning

confidence: 99%

Role of Complement Components in Asthma: A Systematic Review

Tornyi,

Horváth

2024

JCM

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Background: Asthma is a chronic inflammatory airway disease characterized by recurrent symptoms in response to a wide range of external stimuli, including allergens, viral infections, and air pollution together with internal host-derived danger signals. The disease is traditionally associated with adaptive immune responses; recent research emphasizes the critical role of innate immunity in its pathogenesis. The complement system, activated as part of the defense mechanisms, plays a crucial role in bridging innate to adaptive immunity. While experimental models demonstrate complement cascade activation in asthma, human studies remain limited. Methods: This systematic review summarizes existing literature on the complement system in asthma patients, gathering data from PubMed, Web of Science, Scopus, and Google Scholar. The protocol was registered in the OSF. Results: Out of 482 initially identified articles, only 24 met the eligibility criteria, revealing disparities in sample origin, methodologies, and populations. Despite observed heterogeneity, a consistent result was found in the elevation of complement regulatory proteins, such as complement Factor H, in samples from patients with asthma compared to those from healthy subjects. Conclusions: The increased level of regulatory proteins, such as Factor H and I highlight that these may influence asthma pathophysiology. The role of complement factors as potential biomarkers of asthma activity and severity needs further evaluation.

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Section: Discussionmentioning

confidence: 99%

Role of Complement Components in Asthma: A Systematic Review

Tornyi,

Horváth

2024

JCM

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Novel therapeutic receptor agonists and antagonists in allergic conjunctivitis

Abu,

Hehar,

Chigbu

2024

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of review Allergic conjunctivitis is characterized by the development of pathophysiological changes to the ocular surface, which occurs when pro-allergic and pro-inflammatory mediators interact with their cognate receptors expressed on immune and nonimmune cells. Traditional treatments with antihistamines and corticosteroids provide relief, but there is a need for more efficacious and tolerable long-term therapy with a better safety profile. This article aims to provide an overview of the mode of action and clinical application of agonist therapies targeting glucocorticoid, melanocortin, and toll-like receptors, as well as antagonist therapies targeting cytokine, chemokine, integrin, and histamine receptors. Recent findings There has been considerable advancement in immunology and pharmacology, as well as a greater understanding of the cellular and molecular mechanisms of allergic conjunctivitis. Recent research advancing therapy for allergic conjunctivitis has focused on developing synthetic molecules and biologics that can interfere with the process of the allergic immune reaction. Summary This review discusses novel therapeutic receptors being explored agonistically or antagonistically to develop alternative treatment options for allergic conjunctivitis. These novel approaches hold promise for improving the management of allergic eye diseases, offering patients hope for more effective and safer treatment options in the future.

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Transcriptome-Wide Root Causal Inference

Strobl,

Gamazon

2024

Preprint

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Root causal genes correspond to the first gene expression levels perturbed during pathogenesis by genetic or non-genetic factors. Targeting root causal genes has the potential to alleviate disease entirely by eliminating pathology near its onset. No existing algorithm discovers root causal genes from observational data alone. We therefore propose the Transcriptome-Wide Root Causal Inference (TWRCI) algorithm that identifies root causal genes and their causal graph using a combination of genetic variant and unperturbed bulk RNA sequencing data. TWRCI uses a novel competitive regression procedure to annotate cis and trans-genetic variants to the gene expression levels they directly cause. The algorithm simultaneously recovers a causal ordering of the expression levels to pinpoint the underlying causal graph and estimate root causal effects. TWRCI outperforms alternative approaches across a diverse group of metrics by directly targeting root causal genes while accounting for distal relations, linkage disequilibrium, patient heterogeneity and widespread pleiotropy. We demonstrate the algorithm by uncovering the root causal mechanisms of two complex diseases, which we confirm by replication using independent genome-wide summary statistics.

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The complement cascade in lung injury and disease

Cited by 7 publications

References 153 publications

Role of Complement Components in Asthma: A Systematic Review

Role of Complement Components in Asthma: A Systematic Review

Novel therapeutic receptor agonists and antagonists in allergic conjunctivitis

Transcriptome-Wide Root Causal Inference

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