The Role of Complement in the Diagnosis and Management of Allergic Rhinitis and Allergic Asthma

Abstract

Allergic rhinitis and asthma are common chronic inflammatory diseases of the nasal mucus membranes and the upper airways with a high prevalence in Western countries. In addition to maladaptive T-helper type 2 (Th2) immunity, Th17 cells can drive the inflammatory responses in both diseases. Several reports have shown that the complement system is activated locally and systemically in allergic rhinitis and/or allergic asthma patients. Importantly, recent findings in experimental models of allergic rhinitis and allergic asthma suggest that the complement cleavage products complement 3a and complement 5a and the activation of their corresponding receptors in antigen-presenting cells regulate the development of maladaptive Th2 and Th17 immunity. These findings in experimental asthma are corroborated by genome-wide searches and candidate gene studies in humans. We discuss recent findings in experimental and human allergic airway diseases suggesting that complement may serve as a new diagnostic and therapeutic target for both disorders.

Relationship of Circulating C5a and Complement Factor H Levels With Disease Control in Pregnant Women With Asthma

“…11,12,28 C5a may contribute to airway inflammation in asthma, 11,12,28 which was reflected in the correlation between C5a and F ENO levels in non-pregnant subjects with asthma in our study. Furthermore, inhibition of C5a improved lung function, airway hyperreactivity, and airway inflammation in animal models and in mild allergic asthma subjects.…”

“…The complement system plays an important role in the development of asthma 11,12 ; therefore, evaluation of this complex system could potentially help to better understand the disease and may even serve as a biomarker pool for asthma control. This latter possibility is especially important during pregnancy in order to maintain optimal asthma control and thus prevent unwanted effects of the disease on pregnancy outcomes.…”

“…The complement system participates in the pathogenesis of asthma on several levels. 11,12 An interesting element of this complex system is the fragment C5a, because it has a dual role in allergic inflammation. On one hand, it protects against Th2-mediated airway inflammation in the initial phase of sensitization by modulating dendritic cells, but on the other hand, it enhances airway inflammation and hyperreactivity in already established disease.…”

“…On one hand, it protects against Th2-mediated airway inflammation in the initial phase of sensitization by modulating dendritic cells, but on the other hand, it enhances airway inflammation and hyperreactivity in already established disease. 11,12 In the latter case, it behaves as a major pro-inflammatory mediator by promoting chemotaxis and activation of many cell types, which results in release of cytokines, increased vascular permeability, and smooth muscle contraction. Elevated C5a levels were measured not only in bronchoalveolar lavage fluid 13 and induced sputum of subjects with asthma, 14 but also in their plasma 15 ; moreover, plasma levels correlated with asthma severity.…”

Human T cell derived, cell-bound complement iC3b is integrally involved in T cell activation

“…The role of C5a in driving Th17 differentiation and triggering arthritis has also been described [9]. Moreover, recent findings in experimental models of allergic rhinitis and allergic asthma suggest that C3a, C5a and the activation of antigen-presenting cells via their corresponding receptors regulate the development of maladaptive Th2 and Th17 immunity [10]. Our knowledge regarding complement synthesis by human T cells however is sparce, and thorough studies on the interaction of C3 activation fragments and T lymphocytes are not available.…”