Background/Purpose:

IgG4-related disease (IgG4-RD) is a fibroinflammatory condition that may involve essentially any organ. The disease spectrum is also often associated with elevated serum IgG4, and thus serum IgG4 level remains an important biomarker in the diagnosis and monitoring of IgG4-RD. Immunonephelometry is the most common method used internationally to measure IgG4 (and other IgG subclass) levels, with IgG4 test results varying by reagent vendor. Mass spectrometry is a less costly approach pioneered at our institution with fewer errors in the measurement of other subclasses as compared to nephlometry. In this study, we aim to determine the difference in the Binding Site immunonephelometry (BSIN) method and liquid chromatography tandem mass spectrometry (LC-MS/MS), with regard to the respective clinical test characteristics for the diagnosis of IgG4-RD.

Methods:

This retrospective chart review study was approved by the Research Ethics Board at the University of British Columbia. IgG subclass data was retrieved from the laboratory for the period from December 2011 to December 2017. BSIN was the method in use between December 2011 and September 2016, and LC-MS/MS was the method in use from September 2016 to December 2017. For both assays, elevated IgG4 levels were defined as any value above the upper limit of the reference range 1.25 g/L, with both methods calibrated to the same standard. Cases of IgG4-RD were defined as those with histopathologic findings meeting consensus guidelines for IgG4-RD and non-biopsy proven, but possible IgG4-RD cases, were excluded. Only the first IgG4 level at baseline and off of treatment were reported for a given patient using each method. Test performance characteristics were compared using the Fisher exact test.

Results:

In total there were 908 IgG4 subclasses measured. For BSIN, there were 33 IgG4-RD positive cases and 161 disease negative cases. For LC-MS/MS, there were 27 IgG4-RD positive cases and 105 disease negative cases. The IgG4-RD patients in the BSIN group were a mean age of 62 ± 13 years and for LC-MS/MS it was 64 ± 11 years and the sexes were well-matched (2.3:1 versus 2:1 M:F ratio, respectively). False positive diagnoses were comparable between BSIN and LC-MS/MS IgG4 measurements with hypereosinophilic syndrome (n=4; n=1), hypergammaglobulinemia (n=4; n=3) and connective tissue disease (n=3; n=2) being the most common, respectively. The specificity of both BSIN and LC-MS/MS was 85%. Sensitivity was 81% for BSIN and 70% for LC-MS/MS. Positive and negative predictive values, respectively, were 53% and 96% for BSIN and 54% and 92% for LC-MS/MS. The sensitivity and specificity of BSIN versus LC-MS/MS were equivalent (p=0.36, p=1.0).

Conclusion:

Not surprisingly, since the two methods are calibrated to the same standard for IgG4, they have similar sensitivity and specificity for the diagnosis of IgG4-RD. Given the potential advantages, a lower incidence of measurement errors, and a lower cost, the LC-MS/MS could be considered instead of BSIN where possible.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-igg4-test-characteristics-immunonephelometry-versus-liquid-chromatography-tandem-mass-spectrometry/