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Characteristics of monoclonal immunoglobulins that interfere with serum inorganic phosphate measurement
S A Bowles1, R C Tait, S G Jefferson
1Department of Chemical Pathology, Hope Hospital, Salford, UK.
Abstract:
The measurement of inorganic phosphate using an unmodified acid/molybdate assay is known to be subject to interference when paraproteinaemia exists. This phenomenon, due to precipitation in the reaction mixture, is not common to all paraproteins. We studied sera from 35 patients to determine whether interference in the assay was related to particular electrophysical characteristics of the paraproteins. There were spuriously elevated phosphate concentrations in 48.6% of the sera assayed. This could not be related to a direct effect of light chain type, electrical charge or IgG subclass. No IgA paraproteins were found to cause interference but there were immunoglobulin G (IgG) and immunoglobulin M (IgM) paraproteins in both the 'interfering' and 'non-interfering' groups. The median paraprotein concentration was similar in both groups but, where interference occurred, the degree increased in line with the paraprotein concentration. Although it does not seem possible to predict which samples will cause interference, it is important that the clinical implications of this problem are appreciated.
Insights
Paraproteinaemia can interfere with inorganic phosphate measurements, causing falsely elevated results in nearly half of patients. This interference, linked to immunoglobulin G and M paraproteins, increases with paraprotein concentration but is unpredictable.
Area of Science:
- Clinical Chemistry
- Immunology
- Laboratory Medicine
Background:
- Inorganic phosphate measurement using acid/molybdate assays is susceptible to interference in patients with paraproteinaemia.
- This interference is caused by precipitation within the reaction mixture and does not occur with all paraproteins.
Purpose of the Study:
- To investigate whether specific electrophysical characteristics of paraproteins correlate with interference in inorganic phosphate assays.
- To identify potential predictive factors for assay interference in paraproteinaemia.
Main Methods:
- Analysis of sera from 35 patients with paraproteinaemia.
- Evaluation of interference in unmodified acid/molybdate inorganic phosphate assays.
- Correlation of assay interference with paraprotein type (IgA, IgG, IgM), light chain type, electrical charge, and IgG subclass.
Main Results:
- Spuriously elevated phosphate concentrations were observed in 48.6% of assayed sera.
- Interference could not be linked to light chain type, electrical charge, or IgG subclass.
- While IgA paraproteins did not cause interference, both IgG and IgM paraproteins were found in interfering and non-interfering groups. Interference severity increased with paraprotein concentration.
Conclusions:
- The study highlights that paraproteinaemia frequently causes interference in inorganic phosphate measurements, leading to inaccurate results.
- No specific paraprotein characteristic reliably predicts interference, emphasizing the need for clinical awareness.
- The degree of interference is concentration-dependent, underscoring the importance of recognizing this analytical challenge in clinical practice.