Diagnosis of C1 deficiency

Investigation of a patient with an absent total complement

(CH[50]) level

Complement proteins are components of the innate immune system. 

There are 3 pathways to complement activation: 1) the classic

pathway, 2) the alternative (or properdin) pathway, and 3) the lectin

activation (or mannan binding protein, [MBP]) pathway. The classic

pathway of the complement system is composed of a series of

proteins that are activated in response to the presence of immune

complexes. The activation process results in the generation of

peptides that are chemotactic for neutrophils and that bind to immune

complexes and complement receptors. The end result of the

complement activation cascade is the formation of the lytic

membrane attack complex (MAC). 

The first component of complement (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 and

complement deficiency may be an etiologic factor in the development

of autoimmune disease.

Inherited deficiency of C1 is rare. C1 deficiency is associated with

increased incidence of immune complex disease (systemic lupus

erythematosus [SLE], polymyositis, glomerulonephritis, and Henoch-

Schonlein purpura), and SLE is 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's 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 non functional. These rare cases require a functional assay to

detect the deficiency.

34-63 unit/mL

Low levels of complement may be due to inherited deficiencies,

acquired deficiencies, or due to complement consumption (e.g.,

as a consequence of infectious or autoimmune processes).

The measurement of C1q activity is an indicator of the amount of

C1 present. Absent C1q levels in the presence of normal C3 and

C4 values are consistent with a C1 deficiency. Low C1q levels in

the presence of low C4 but normal C3 may indicate the presence

of an acquired inhibitor (autoantibody) to C1 esterase inhibitor.

The total complement assay (#8167 "Complement, Total, Serum")

should be used as a screen for suspected complement

deficiencies before ordering individual complement component

assays. A deficiency of an individual component of the complement

cascade will result in an undetectable CH50.

Absent (or low) C1q functional levels in the presence of normal C1q

antigen levels should be replicated with a new serum specimen to

confirm that C1q inactivation did not occur during shipping.

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