Westwood, J-P; (2015) The Role of Complement Anaphylatoxins in Systemic Disease. Doctoral thesis , UCL (University College London).

Abstract

The complement system has a vital role both in innate and adaptive immunity. Study of diseases associated with defective complement regulation has shown the harmful effects of inappropriate and/or excessive complement activation to the host organism. The hypothesis for this thesis is that complement activation is a feature of the acute phase of several disorders, and that complement overactivation - characterized by high levels of the anaphylatoxins C3a and C5a - has a pathological role, with high levels being associated with a worse prognosis. Complement anaphylatoxins were measured in patients hospitalized with community acquired pneumonia, and patients with exacerbations of chronic obstructive pulmonary disease (COPD). Patients with thrombotic thrombocytopenic purpura (TTP) were also studied in detail: following a retrospective review of the role of immunosuppression with rituximab in these patients, a prospective study was performed to compare complement levels in acute disease with remission cases. Complement activation was present in the acute phase of all diseases studied, but there was a considerable variation in levels between cases. High systemic levels of complement anaphylatoxins were seen in several patients, but there was no clear association with prognosis; however in patients with COPD changes in sputum complement levels were associated with a longer time to clinical recovery. Patients with TTP generally had higher levels during the acute phase of the disease, and a positive correlation was found between complement activation and the level of antibody mediating the disease.

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