During immune complex reactions, certain complement proteins become physically bound to the tissue in which the immunologic reaction is occurring. These proteins can be demonstrated in tissue by appropriate immunopathologic stains. The most frequent evaluation of complement is by serum or plasma assay (Table 1). Complement components (e.g., C3 and C4) can be assessed by nephelometry. These assays are useful for the diagnosis and monitoring of patients.

Table1. Interpretation of Complement Activation by Individual Components

Assessment of Complement

The procedures discussed next can be used in diagnostic immunology.

C1 Esterase Inhibitor (C1 Inhibitor)

C1 measures the activity and concentration of C1 inhibitor in serum. A deficiency of this protein is characteristic of hereditary angioedema (HAE; see later). Some patients demonstrate catalytically inactive protein.

C1r, C1s, C2, C3, C4, C5, C6, C7, C8

Homozygous deficiencies predispose a patient to autoimmune disease (especially SLE) and to arthritis, chronic glomerulonephritis, infections, and vasculitis.

C1q

The complement component C1q is evaluated in serum. Decreased levels can be demonstrated in patients with hypocomplementemic urticarial vasculitis, severe combined immunodeficiency (SCID), or X-linked hypogammaglobulinemia.

C1q Binding

This procedure measures the binding of immune complexes containing IgG1, IgG2, or IgG3 and IgM to the complement component C1q. High values of C1q binding are associated with the presence of circulating immune complexes of the type that interacts with the classic pathway of complement activation. This test can be useful as a prognostic tool at diagnosis and during remission of acute myelogenous leukemia.

C2

The most common complement deficiency is of C2. It is an autosomal recessive disorder; the C2 gene is on chromosome 6 in the major histocompatibility complex (MHC). The incidence is 1:28,000 to 1:40,000; the carrier state is 1.2% in the general population.

Half of patients with homozygous C2 deficiency have no symptoms; those with symptoms have infections with S. pneumoniae, N. meningitidis, and H. influenzae. Of symptomatic patients, 50% exhibit a lupus-like disorder with photosensitivity and rash.

C3

Also an acute-phase protein, elevated C3 levels can indicate an acute inflammatory disease. Although C3 lies at the junction of the two pathways, it is much more severely depressed when activation occurs via the alternative pathway. Extremely decreased levels are seen in patients with poststreptococcal glo merulonephritis and in those with inherited (C3) complement deficiency. This component is also decreased in cases of severe liver disease and in SLE patients with renal disease.

C3b Inhibitor (C3b Inactivator)

The C3b component of complement causes low complement C3 levels, the absence of C3PA in serum, and high C3b levels. A deficiency of C3b inhibitor is associated with an increased predisposition to infection.

C3PA (C3 Proactivator, Properdin Factor B)

 The factor B component is consumed by activation of the alternative complement pathway. Assessment of C3PA indicates whether a decreased level of C3 results from the classic or alternative pathways of complement activation. Decreased levels of C3 and C4 demonstrate activation of the classic pathway. Decreased levels of C3 and C3PA with a normal level of C4 indicate complement activation via the alternative pathway (Table 1).

Activation of the classic pathway (and sometimes with accompanying alternative pathway activation) is associated with disorders such as immune complex diseases, various forms of vasculitis, and acute glomerulonephritis. Activation of the alternative pathway is associated with many disorders, including chronic hypocomplementemic glomerulonephritis, disseminated intravascular coagulation (DIC), septicemia, subacute bacterial endocarditis, PNH, and sickle cell anemia.

In SLE, both the classic and alternative pathways are activated.

C4

The C4 level often provides the most sensitive indicator of dis ease activity. C4 is also an acute-phase reactant. Elevated C4 levels can indicate an acute inflammatory reaction or a malignant condition. Measurement of C4 may demonstrate inflammation or infection long before it is clinically evident by standard assessment methods (e.g., total white blood count [WBC] and leukocyte differential, febrile response, or elevated erythrocyte sedimentation rate [ESR]).

C4 is destroyed only when the classic pathway is activated. A decreased C4 level with elevated anti–n-DNA and antinuclear antibody (ANA) titers confirm the diagnosis of SLE in a patient. In these cases of SLE, the periodic assessment of C4 can be useful for monitoring the progress of the disorder. Patients with extremely low C4 levels in the presence of nor mal levels of the C3 component may be demonstrating the effects of a genetic deficiency of C1 inhibitor or C4. Reduction of C3 and C4 components implies that activation of the classic pathway has been initiated.

C4 Allotypes

 The antigenically distinct forms of C4A and C4B are located on chromosome 6 in the MHC. C4 allotypes in conjunction with specific human leukocyte antigens (HLAs) are markers for disease susceptibility .

C5

A genetic deficiency of the C5 component is associated with increased susceptibility to bacterial infection and is expressed as an autoimmune disorder (e.g., SLE). Patients with dysfunction of C5 (Leiner’s disease) are predisposed to infections of the skin and bowel, characterized by eczema. Their C5 level is nor mal, but the C5 component fails to promote phagocytosis.

C6

 A decreased quantity of C6 predisposes an individual to significant neisserial (bacterial) infections.

 C7

A decreased level of C7 is associated with Raynaud’s phenomenon, sclerodactyly, telangiectasia, and severe bacterial infections caused by Neisseria spp.

 C8

A decreased quantity of C8 is associated with SLE. A C8 deficiency makes patients highly susceptible to Neisseria infections.

Select Complement Deficiencies

 Properdin Deficiency

Properdin acts to stabilize the alternative pathway C3 convertase (C3bBb). A deficiency leads to bacterial infections, often meningococcemia. This disorder is an X-linked recessive trait.

Hereditary Angioedema

This disorder is a deficiency in a complement protein. Infections are not usually a significant problem. HAE is autosomal dominant, unlike other complement deficiencies. Two types exist, type 1 (low antigen level and low functional protein) and type 2 (normal antigen level with low function).

Familial Mediterranean Fever

This defect in protease in peritoneal and synovial fluid is trans mitted as an autosomal recessive trait on chromosome 16. Patients with this defect experience recurrent episodes of fever and inflammation in the joints and pleural and peritoneal fluids.

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مواضيع ذات صلة

Hematopoietic Stimulators

Biological Functions of Complement Proteins

The Complement System: Alternative Pathway

The Complement System: Classic Pathway

The Complement System

Immune-Mediated Disease

Evaluation of Immunodeficiency Syndromes

Plasma Cell Biology

B Lymphocyte Subsets

Natural Killer and K-Type Lymphocytes

Antigen Recognition by T Cells

Antigen Processing and Antigen Presentation to T Cells