Non-Heterophile Antibody Interference with Falsely Elevated Results

Endogenous antibodies and binding proteins can also lead to falsely elevated test results. A notable example involves prolactin, which exists in multiple molecular forms: the biologically active monomeric prolactin (~23 kDa), along with dimeric prolactin (~50 kDa) and macroprolactin (>100 kDa), the latter being a complex of prolactin with immunoglobulin G (IgG). While macroprolactin is biologically inactive, it has preserved immunoreactivity and therefore is still detected by most immunometric assays, resulting in falsely elevated prolactin levels.

To detect macroprolactin interference, polyethylene glycol (PEG) precipitation is a widely used and cost-effective method. PEG removes macroprolactin by precipitation, allowing only monomeric prolactin to remain in the supernatant. A PEG-precipitable prolactin fraction exceeding 60% suggests significant macroprolactinemia, helping distinguish it from true hyperprolactinemia.

Macro-TSH represents another example of this phenomenon, potentially causing falsely elevated TSH levels.

References

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