IgM IgG IgG Avidity

IgM

What it means

  • Marker of recent immune activation
  • Appears early after primary infection

What it does NOT reliably mean

It does not always mean recent infection

IgM can:

  • Persist for months
  • Reappear with reactivation
  • Be falsely positive

IgG

What it means

  • Evidence of exposure at some point in life
  • Appears later than IgM
  • Persists lifelong

What it does NOT tell you

  • When the infection occurred
  • Whether it is active or remote

IgG

What it means

  • Evidence of exposure at some point in life
  • Appears later than IgM
  • Persists lifelong

What it does NOT tell you

  • When the infection occurred
  • Whether it is active or remote

IgG avidity (this is the key discriminator)

What avidity measures

  • The binding strength of IgG antibodies
  • Increases over time as immune response matures

Interpreting IgG avidity

Low avidity

  • IgG is immature
  • Infection occurred recently
  • Typically within:
  • Last 8–12 weeks (depends on pathogen)
  • → Strong evidence of primary infection

High avidity

  • IgG is mature
  • Infection occurred well before pregnancy or early in first trimester
  • → Effectively rules out recent primary infection

This is the single most powerful test for dating infection in pregnancy.

Pattern 1: IgM negative, IgG negative

  • No prior exposure
  • Susceptible
  • No infection yet
  • → Repeat only if clinical suspicion or exposure

Pattern 2: IgM positive, IgG negative

  • Very early primary infection
  • Or false-positive IgM
  • → Repeat in 1–2 weeks to document IgG seroconversion

Pattern 3: IgM positive, IgG positive, low avidity

This is the classic primary infection pattern.

Meaning:

  • Recent primary infection
  • High fetal transmission risk (for CMV, toxo, rubella)
  • → Amniocentesis is indicated (timed appropriately)

Pattern 4: IgM positive, IgG positive, high avidity

This is where most confusion happens.

Meaning:

  • Past infection
  • IgM persistence or reactivation
  • Not a recent primary infection
  • → Amniocentesis usually NOT indicated, unless ultrasound abnormal

Pattern 5: IgM negative, IgG positive, high avidity

  • Remote infection
  • Immune
  • No fetal risk
  • → No further action

Role of serial titres (very important, but limited)

What serial titres can do

  • Demonstrate seroconversion
  • Demonstrate rising IgG titres

What serial titres cannot reliably do

  • Distinguish primary infection from reactivation once IgG is already present
  • Date infection precisely without avidity

Seroconversion

Definition:

Change from IgG negative → IgG positive

This is proof of primary infection.

If this happens during pregnancy:

→ High fetal risk

→ Amniocentesis indicated

Rising IgG titres

A fourfold rise suggests recent infection

But:

  • Titres vary between labs
  • Reactivation can also cause rises
  • Less reliable than avidity

Amniocentesis is justified when ALL apply:

Evidence of primary maternal infection

Low IgG avidity

OR documented seroconversion

Appropriate gestational timing

Usually = 21–22 weeks

And = 6–7 weeks after presumed infection

Testable pathogen in amniotic fluid:

CMV PCR

Toxo PCR

Rubella PCR

Amniocentesis is NOT usually justified when:

  • IgG avidity is high
  • Only IgM is positive
  • No seroconversion
  • Ultrasound is normal