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Serum IgG2 and tissue IgG2 plasma cell elevation in orbital IgG4-related disease (IgG4-RD): Potential use in IgG4-RD assessment.
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    Spurious elevations in serum IgG2 may be seen by immunonephelometry in IgG4-RD - response to Chan et al [1]
    • Andre Mattman, Medical Biochemist Dept of Pathology and Laboratory Medicine, St Paul’s Hospital
    • Other Contributors:
      • Jessica Grace van der Gugten, Laboratory Scientist
      • Mari L DeMarco, Clinical Chemist
      • Mollie Carruthers, Rheumatologist
      • Alex Chin, Clinical Chemist
      • Luke YC Chen, Hematologist
      • Daniel T Holmes, Medical Biochemist

    Chan et al report on marked elevations in serum IgG2 that are observed in patients with orbital IgG4 related disease (IgG4-RD), with or without systemic involvement.

    Using ROC area under the curve comparisons, the authors show that the serum IgG2 concentration has a higher AUC (0.9) than serum IgG4 (0.8) in detecting IgG4-RD in their cohort (comprised of 33 subjects: 20 with orbital IgG4-RD with or without systemic involvement, and 13 with non-IgG4-RD orbital inflammation).

    Our group has noted this paper by Chan et al with interest as we have observed the same phenomenon of marked serum IgG2 elevations in patients with IgG4-RD, who have concomitantly low serum IgG4 concentrations. Like the patients presented by Chan et al, our IgG4-RD patients uniformly had serum IgG2 concentrations that were greater than the serum IgG4 concentration, even when the serum IgG4 concentration was very high.

    Our interpretation of the apparent superior clinical utility of the serum IgG2 test in this context, is that this observation is only made when using an immunonephelometric methodology subject to two different types of analytical error:
    i) antigen excess, leading to falsely low serum IgG4 measurement in a patient who in fact has a marked elevation of serum IgG4 [2] and
    ii) cross reactivity of the reagent used to measure IgG2 with serum IgG4, leading to falsely high serum IgG2 measurement (this may be due to a direct and specific recognition of IgG4 epitop...

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    Conflict of Interest:
    None declared.