Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (828 page)

COMBINED FIRST-TRIMESTER AND SECOND-TRIMESTER SCREENING (INTEGRATED/SEQUENTIAL SCREENING)

See Prenatal Screening.

COMPLEMENT SYSTEM ASSAYS
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   Definition

   The complement system is a major component of innate and adaptive immunity; upon activation, the complement results in the formation of the membrane attack complex (MAC) that releases peptides called anaphylatoxins. About 90% of complement components are synthesized in the liver and are acute-phase proteins.

   There are three pathways of activation: Classical (antibody-sensitized cells), alternative (early defense against microorganisms), and mannose-binding lectin (MBL) (recognizes microorganisms in the absence of antibodies that are replaced by a lectin, such as mannose-binding protein [MBP]). MBL is formed in the liver. It belongs to a family of molecules called collectins. Many components of the complement system interact through cascading mechanisms. The nine components of the classical pathway are designated by the upper case letter C, followed by a number indicating the order of appearance during the cascading sequence (the only exception is C4, which acts before C2). The components of the alternate pathway are called factors and are designated by upper-case letters (example: factor H, factor D). For the MBL pathway, the components are referred to by the abbreviations of the proteins’ names.

   All three pathways of complement activation converge at the activation of C3 and assembly of the membrane attack complex, which is formed by components C5–C9.

   Use

   Complement should be investigated in patients with recurrent pyogenic infections (but with normal white cell counts and immunoglobulins), recurrent angioedema, cryoglobulinemic vasculitis, and with multiple family members with recurrent neisserial infections. Patients with deficiencies in the alternate pathway factors D, B, P, H, and I, or the late complement components C3, C5–C9, are particularly susceptible to infections with
Neisseria meningitidis
.

   To determine the presence of deficiencies of individual components, and
whether the deficiency is acquired or inherited
.

   The total hemolytic complement assay (CH50 or THC) is a global test; it is decreased if any of the components of the classical pathway are deficient. The AH50 assay screens for abnormalities in the alternate pathway. The use of CH50 and AH50 assays allows identification of abnormalities in both pathways. When the CH50 is very low, the next step is to measure specific complement components.

   Normal Ranges

   Complement levels are determined by immunologic and functional assays.

   The most commonly used assays are C3, C4, CH50, and AH50 (see Complement Components in Plasma and Their Deficiencies table).

   Interpretation