# Complement Deficiency Workup

> Complement deficiency workup: CH50 versus AH50, recurrent Neisseria and SLE-like states for NEET-PG Medicine aspirants.

- Canonical URL: https://prepelephant.com/topics/neet-pg/medicine/complement-deficiency-workup
- Exam / course: NEET-PG · Subject: Medicine
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-02
- Last updated: 2026-10-02
- How to cite: "Complement Deficiency Workup", PrepElephant, https://prepelephant.com/topics/neet-pg/medicine/complement-deficiency-workup

## Direct answer

Recurrent meningococcal disease with otherwise normal immunity points to the terminal complement pathway (C5–C9), where deficiency raises the lifetime risk of Neisseria invasion by up to thousands-fold, and the screening tool is a CH50 that comes back essentially zero rather than merely low. Combining CH50 with AH50 maps the lesion: both absent means terminal-component deficiency, CH50 absent with AH50 intact means classical pathway (C1q, C1r/s, C2, C4), AH50 absent with CH50 normal means alternative pathway (properdin, factor D, factor B). Early classical-component deficiencies instead produce SLE-like disease — the second face of complement deficiency every NEET-PG Medicine candidate must recognise.

## What you must remember

- CH50 assays classical plus terminal pathway function; it is near-zero in any component deficiency of that route and merely reduced with consumption (SLE, immune-complex disease, cryoglobulinaemia).
- AH50 assays the alternative pathway; the CH50/AH50 pair localises the deficient arm.
- Both near-zero: terminal pathway C5–C9; CH50 zero with AH50 normal: classical pathway; AH50 zero with CH50 normal: alternative pathway.
- Terminal C5–C9 deficiency: recurrent meningococcal meningitis or meningococcaemia, often with milder-than-expected first episodes; properdin deficiency is X-linked with the same phenotype.
- Early classical deficiency (C1q, C1r/s, C4, C2): SLE-like illness with photosensitive rash and low complement; C1q deficiency carries the highest SLE risk, C2 deficiency is the commonest classical deficiency in Caucasian populations.
- C3 deficiency: severe recurrent pyogenic infections with encapsulated bacteria, immune-complex disease.
- Factor H, factor I or CD46 deficiency: complement-mediated thrombotic microangiopathy (atypical haemolytic uraemic syndrome).
- C1-inhibitor deficiency: hereditary angioedema — the exam's bridge protein.
- Management of late-component deficiency: meningococcal ACWY plus MenB vaccination, pneumococcal and Hib immunisation, an antibiotics-at-first-symptoms plan, and family counselling with screening.
- Mannose-binding lectin deficiency: mostly minor childhood infection susceptibility, largely clinically silent in adults.

## How to work through a typical case

A 19-year-old college student is admitted with his second episode of meningococcal meningitis in three years; immunoglobulins, HIV serology, full blood count and metabolic screen are normal, and he has no splenectomy history.

Step one: recognise the pattern — recurrent invasive Neisseria disease with otherwise intact immunity is the terminal-complement phenotype until excluded. Step two: order the functional screen first, CH50; a result near zero in a well patient indicates a component deficiency, whereas a moderately low value in an ill, immune-complex-loaded patient suggests consumption. Step three: localise with AH50 — his AH50 also near-zero places the defect in the shared terminal pathway (C5–C9), and specific assays for individual components confirm, C9 deficiency being notably prevalent in Japanese populations. Step four: manage immediately and concretely — quadrivalent ACWY and MenB vaccination (infection can still occur despite vaccination, so counsel fast access to antibiotics), pneumococcal and Hib cover, a written "fever means emergency" plan, and avoidance where practical of dormitory crowding during outbreaks. Step five: extend to the family — screen siblings with CH50 given the autosomal recessive inheritance, and counsel on cascade testing before high-risk settings such as military recruitment or Hajj travel. Step six: contrast the other face aloud for completeness — had this patient presented with photosensitive rash, arthritis and low C3/C4, the working diagnosis would be lupus from early classical deficiency, and the CH50 would still be near zero but the clinical route entirely different.

## Where students slip

First, ordering C3 and C4 alone and declaring the workup complete — functional CH50 is the deficiency screen; antigen levels only map selected components. Second, confusing "low CH50 in active SLE" (consumption, rises with treatment) with "absent CH50 in a well patient" (deficiency, permanent). Third, forgetting the SLE-like face of early classical deficiency when a stem pairs photosensitivity with absent CH50. Fourth, missing properdin as the X-linked alternative to autosomal recessive terminal defects in a family history of affected males. Finally, offering vaccination as fully protective — terminal-deficiency patients still contract meningococcal disease, so the emergency-antibiotic plan is part of the answer, not an optional extra.

## Frequently asked questions

### Which screening test detects classical complement pathway deficiency?
CH50 — a near-zero result in an otherwise well patient indicates deficiency somewhere in the classical or terminal pathway, unlike the moderate reduction of consumption.

### How do CH50 and AH50 together localise a complement deficiency?
Both absent points to the shared terminal pathway (C5–C9); absent CH50 with normal AH50 indicates classical pathway deficiency; absent AH50 with normal CH50 indicates alternative pathway deficiency.

### Which infections dominate terminal complement deficiency?
Recurrent Neisseria meningitidis meningitis and meningococcaemia, with lifetime risk increased up to thousands-fold; gonococcal infection is also increased.

### Which complement deficiencies produce an SLE-like syndrome?
Early classical pathway defects — C1q (highest risk), C1r/s, C4 and C2 — presenting with photosensitive rash, immunopathology and characteristically absent CH50.

### How are patients with terminal complement deficiency managed?
Meningococcal ACWY and B, pneumococcal and Haemophilus vaccinations, a rapid-access antibiotic plan for fever, counselling that vaccination is imperfect, and family screening by CH50.