Total IgG method insensitivity to the presence of IgG4 immunoglobulins

Objective: IgG4 related disease (IgG4RD) is detected in part by measurement of serum IgG4 levels in patients suspected to have the condition. The immunonephelometric methods that are used to measure serum IgG4 are susceptible to hook effect errors. The quality control parameter IgGRDiff=100∗[Sum (IgG1, IgG2, IgG3, IgG4)-Total IgG]/Average [Sum (IgG1, IgG2, IgG3, IgG4), Total IgG] is theoretically of use in detecting large IgG4 hook effect. We evaluated the IgGRDiff parameter in this context.

Design and methods: Retrospective review of the IgGRDiff parameter in a cohort of patient samples. All samples were tested with the Siemens BNII analyzer utilizing Siemens (total IgG) and Binding Site (IgG subclass) reagents. The 95th percentile for the absolute value of IgGRDiff was determined and compared to the IgGRDiff values for the samples with known hook effect error. IgGRDiff was regressed against IgG4Rsum [IgG4Rsum=100∗IgG4/(IgG1+IgG2+IgG3+IgG4)].

Results and discussion: The 95th percentile of the absolute value of the IgGRDiff parameter was 22.8% in our study sample set (n=163). The absolute value of the IgGRDiff was <22% in 4/6 cases indicating low sensitivity of IgGRDiff in identifying IgG4 hook effect errors. IgG4Rsum was directly correlated with IgGRDiff (IgGRDiff=1.21∗IgG4Rsum-7.9, R(2)=0.62) indicating that the total IgG measurement has little or no reactivity with IgG4 immunoglobulins.

Conclusions: The Siemens' Total IgG method is insensitive to IgG4 and should not be used as a quality control parameter to detect IgG4 hook effect.