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The C1 inhibitor deficiency. A review
1Laboratoire de Biochimie Médicale, Cliniques Universitaires Saint Luc, Bruxelles, Belgique.
Insights
C1 inhibitor (C1I) deficiency, a common complement system defect, causes angioedema. Diagnosing hereditary and acquired forms requires assessing C1 inhibitor protein levels and function for effective treatment.
Area of Science:
- Immunology
- Complement System Biology
- Protease Inhibitor Research
Background:
- C1 inhibitor (C1I) is crucial for regulating the complement system's classical pathway.
- C1I deficiency is the most frequent genetic defect in the complement system, leading to angioedema.
- Angioedema, characterized by swelling, can be hereditary (three types) or acquired (malignancy- or autoimmune-associated).
Purpose of the Study:
- To highlight the significance of C1 inhibitor (C1I) in complement regulation and angioedema pathogenesis.
- To differentiate between hereditary and acquired C1 inhibitor deficiencies.
- To review diagnostic methods for C1 inhibitor deficiencies.
Main Methods:
- Review of existing literature on C1 inhibitor function, deficiency, and angioedema.
- Analysis of diagnostic approaches for C1 inhibitor assessment.
- Categorization of C1 inhibitor deficiencies into hereditary and acquired forms.
Main Results:
- C1 inhibitor deficiency is linked to hereditary angioedema (insufficient production or abnormal protein) and acquired angioedema (malignancy or autoimmune related).
- Angioedema symptoms include swelling in extremities, face, airways, and viscera.
- Treatment options include androgens, antifibrinolytics, and C1 inhibitor concentrate.
Conclusions:
- Accurate diagnosis distinguishing C1 inhibitor protein levels and functional activity is essential.
- Various assays (e.g., ELISA, hemolytic assays) aid in diagnosing C1 inhibitor deficiencies.
- Improved diagnosis is key to effective management and treatment of angioedema.
Abstract:
C1 inhibitor (C1I), a member of the serine protease inhibitor superfamily, is the principal regulator of the activation classical pathway of complement by reducing the proteolytic activity of activated C1r and C1s. A deficiency of active C1 inhibitor is the most commonly identified genetic defect of the complement system. It is associated with a pathology called angioedema. There are three forms of hereditary angioedema. The first type is characterized by an insufficient production of a normal protein. The two other forms are characterized by the presence of an abnormal C1 inhibitor protein. Moreover a reduction of functional C1 inhibitor may also be acquired. There are two types of acquired angioedema, a form associated with malignancy (B cell lineage, breast cancer, ...) and an autoimmune form. Angioedema manifests itself by attacks of swelling of the extremities, face, trunk, airways, or abdominal viscera, occurring spontaneously or as a result of trauma. Three main categories of substances have been proposed for the treatment of C1 deficiencies: the androgens, the antifibrinolytics and fresh plasma or purified C1 inhibitor. To distinguish between the different forms of C1 inhibitor deficiencies, it is necessary to determine the amount of C1 inhibitor protein and the level of its functional activity. Several methods for the determination of C1 inhibitor have been proposed: titrimetric and spectrophotometric assays, inhibition of complement haemolytic activity, radioimmunoassay, enzyme-linked immunosorbent assay, ...), in order to improve the diagnosis and the treatment of angioedema.