Complement as a diagnostic tool in immunopathology

Abstract

The complement system is a complex and autoregulated multistep cascade at the interface of innate and adaptive immunity. It is activated by immune complexes or apoptotic cells (classical pathway), pathogen-associated glycoproteins (lectin pathway) or a variety of molecular and cellular surfaces (alternative pathway). Upon activation, complement triggers the generation of proteolytic fragments that allow the elimination of the activating surface by enhancing inflammation, opsonization, phagocytosis, and cellular lysis. Moreover, complement efficiently discriminates self from non-self surfaces by means of soluble and membrane-bound complement regulators which are critical for innate self-tolerance. Complement deficiency or dysfunction disturb complement homeostasis and give rise to diseases as diverse as bacterial infections, autoimmunity, or renal and neurological disorders. Research on complement-targeted therapies is an expanding field that has already improved the prognosis of severe diseases such as atypical Haemolytic Uremic syndrome or Paroxysmal Nocturnal Haemoglobinuria. Therefore, complement analysis and monitoring provides valuable information with deep implications for diagnosis and therapy. In addition to its important role as an extracellular defense system, it has now become evident that complement is also present intracellularly, and its activation has profound implications for leukocyte survival and function. In this review, we summarize the essential, up-to-date information on the use of complement as a diagnostic and therapeutic tool in the clinics.

Plasma levels of soluble membrane attack complex are elevated despite viral suppression in HIV patients with poor immune reconstitution

“…Recent mechanistic insights into complement biology and biochemistry have led to a therapeutic revolution targeting complement‐mediated immunopathology in multiple diseases . A number of complement inhibitors are now in clinical trials, and new questions have arisen: how should clinicians monitor the effectiveness of these treatments at the level of complement activity, and which complement proteins or activation fragments can serve as clinically useful biomarkers ?…”

Immunological features of patients affected by Barraquer-Simons syndrome

“…In that study, most patients with C3 consumption had detectable levels of an IgG/IgM autoantibody called C3 nephritic factor (C3NeF). C3NeF stabilizes the enzymatic complex C3 convertase (C3bBb), which causes unopposed activation of the alternative pathway (AP) of the complement system [9]. The presence of this autoantibody has been associated with a rare entity named C3 glomerulopathy (C3G) [10].…”

Doenças associadas à deficiência do sistema complemento

“…Na deficiência do SC ocorre uma disfunção da homeostasia do próprio complemento, podendo aumentar a suscetibilidade ao desenvolvimento de doenças autoimunes, infecções bacterianas e distúrbios renais e neurológicos. Tais deficiências podem ser hereditárias ou adquiridas 3 .…”