Complement proteins are components of the innate immune system. There are 3 pathways to complement activation: 1) the classical pathway, 2) the alternative (or properdin) pathway, and 3) the lectin (or mannan binding lectin) pathway. The classical pathway of the complement system is composed of a series of proteins that are activated in response to the presence of immune complexes. A single IgM molecule or 2 IgG molecules are sufficient to trigger activation of the recognition complex initiated by C1q. The activation process triggers a cascade that includes an amplification loop. The amplification loop is mediated by C3, with cleavage of a series of proteins, and results in 3 main end products: 1) anaphylatoxins that promote inflammation (C3a, C5a), 2) opsonization peptides that are chemotactic for neutrophils (C3b) and facilitate phagocytosis, and 3) the membrane attack complex, which promotes cell lysis.
C1 is composed of 3 subunits designated as C1q, C1r, and C1s. C1q recognizes and binds to immunoglobulin complexed to antigen and initiates the complement cascade. Congenital deficiencies of any of the early complement components (C1-C4) result in an inability to generate the peptides that are necessary to clear immune complexes and to attract neutrophils or generate lytic activity. These patients have increased susceptibility to infections with encapsulated microorganisms. They may also have symptoms that suggest autoimmune disease in which complement deficiency may be an etiologic factor.
Inherited deficiency of C1 is rare. Just over 40 cases have been reported for C1q deficiency, and another 20 cases have been described for C1s and C1r deficiency. C1 deficiency is associated with increased incidence of immune complex disease (systemic lupus erythematosus [SLE], polymyositis, glomerulonephritis, and Henoch-Schonlein purpura), with SLE the most common manifestation of C1 deficiency. The SLE associated with C1 deficiency is similar to SLE without complement deficiency, but the age of onset is often prior to puberty.
Low C1 levels have also been reported in patients with abnormal immunoglobulin levels (Bruton and common variable hypogammaglobulinemia and severe combined immunodeficiency), and this is most likely due to increased catabolism.
Complement levels can be detected by antigen assays that quantitate the amount of the protein. For most of the complement proteins a small number of cases have been described in which the protein is present but is nonfunctional. These rare cases require a functional assay to detect the deficiency.