C3, C4 is what we usually order.
The classical complement pathway activates C4 as well as C3. This can lead to low C3 and C4 levels which lead to decreased CH 50. This would typically be seen with complement activation driven by immune complexes (lupus, hepatitis C, cryoglobulinemia).
Alternative complement pathway activation is typically driven by bacterial or microbial antigens: C3 is directly activity producing low C3 and decreased CH 50 C4 is normal. C3 may also be directly activated by C3 nephritic factor which is an antibody which activates C3 convertase directly (associated with dense deposit disease).
Diseases which do not have bacterial/microbial antigens or circulating immune complex will typically have normal levels of serum complement and normal CH 50. IgA nephritis does not cause low serum complements as IgA is a poor complement activator. ANCA diseases do not produce circulating immune complexes, for us, complement levels are normal. For unclear reasons, anti-GBM disease typically presents with normal complement levels
Six classical diseases come to mind when one sees low C3 and low C4.
Subacute bacterial endocarditis
MPGN 1 and 2
Cryoglobulinemic glomerulonephritis ( usually c4 more than c3)
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