|Values are valid only on day of printing.|
Investigation of suspected alternative pathway complement deficiency, atypical hemolytic uremic syndrome, C3 glomerulonephritis, dense-deposit disease
Complement proteins are components of the innate immune system. There are 3 pathways to complement activation: the classic pathway, the alternative (or properdin) pathway, and the lectin activation (or mannose-binding protein: MBP) pathway.
The total hemolytic complement (CH50) assay (COM / Complement, Total, Serum) is the best screening assay for most complement abnormalities. It assesses the classical complement pathway including early components that activate the pathway in response to immune complexes, as well as the late components involved in the membrane attack complex. The CH50 assay will be abnormal if there are specific hereditary or acquired C1-C9 complement component deficiencies or if there is consumption of complement due to immune (or autoimmune) complexes.
The complement alternate pathway (AH50) assay is a screening test for complement abnormalities in the alternative pathway. The alternate pathway shares C3 and C5-C9 components, but has unique early complement components designated factors D, B, and P, as well as regulatory factors H and I. This pathway is activated by microbial polysaccharides and does not require immune complex formation. Patients with disseminated infections with pyogenic bacteria in the presence of a normal CH50 may have an absent AH50 due to hereditary or acquired deficiencies of the alternate pathway. Patients with deficiencies in the alternate pathway factors (D, B, P, H, and I) or late complement components (C3, C5-C9) are unusually susceptible to recurrent neisserial meningitis. The use of the CH50 and AH50 assays allow identification of the specific pathway abnormality.
Unregulated alternative pathway can also result in disease. The majority of these diseases present with renal function impairment such as atypical hemolytic uremic syndrome (a-HUS), dense deposit disease (DDD), and C3 glomeulonephritis (C3GN).
> or =46% normal
Absent complement alternate pathway (AH50) in the presence of a normal total hemolytic complement (CH50) suggests an alternate pathway component deficiency.
Normal AH50 with absent CH50 suggests an early (C1, C2, C4) classic pathway deficiency.
Absent AH50 and CH50 suggests a late (C3, C5, C6, C7, C8, C9) component deficiency or complement consumption.
Absent AH50 and CH50 in the presence of a normal C3 and C4 suggests a late (C5, C6, C7, C8, C9) component deficiency.
The AH50 assay is a functional test and is dependent on correct sampling, storage, and shipping conditions.
An absent AH50 should be confirmed with a repeat test on a different specimen.
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3. Frank MM: Complement deficiencies. Pediatr Clin North Am 2000;47(6):1339-54