Laboratory tests - C3 and C4

Role

Serum complement C3 and C4 levels are used in rheumatology principally to assess disease activity and monitor treatment response in SLE, where complement consumption reflects active immune complex-mediated disease
Routinely monitored alongside anti-dsDNA titre in known SLE, and checked as part of the initial workup when SLE or another immune complex-mediated disease is suspected

Active immune complex deposition (classically in lupus nephritis) consumes complement via the classical pathway - C1q binds immune complexes, triggering sequential activation and consumption of C4 then C3 - falling C3/C4 with rising anti-dsDNA titre is a classic pattern preceding or accompanying an SLE flare, particularly lupus nephritis

Low C3/C4 in the correct clinical context supports active immune complex-mediated disease; normal or rising complement during a suspected flare should prompt reconsideration of the cause (e.g. infection, or a flare not primarily immune-complex-mediated)
Distinguish acquired complement consumption (active SLE) from primary/hereditary complement deficiency (see complement deficiencies) - the latter is a fixed, lifelong low level rather than a marker that fluctuates with disease activity

Trending C3/C4 alongside anti-dsDNA and clinical assessment guides treatment intensity decisions in known SLE - a falling trend supports escalating immunosuppression even before overt clinical flare symptoms are apparent in some patients
Renal function/urinalysis monitoring alongside complement levels, given the specific association with lupus nephritis

SLE and lupus nephritis, anti-dsDNA antibody monitoring, hereditary complement deficiency (a distinct entity, not a marker of disease activity)

C3/C4 and anti-dsDNA trends are used together, not in isolation, since not every SLE patient's complement/antibody levels track reliably with disease activity - the individual patient's own historical pattern is often more informative than a single result compared against a population reference range

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