IgG and the sum of ohe subclasses: what is it good for?

Abstract

Determination of IgG subclasses has a role in the diagnosis of IgG4 disease, and possibly IgG subclass deficiency. It is recommended that the total IgG level be measured as a quality check, with the requirement that the sum of the subclasses be within 15%. Although widely adopted, there seems little scientific justification for such an approach. We performed a prospective audit of 297 samples sent for IgG subclass measurement. Fifty of 297 samples failed the 15% rule; subsequently, eight passed on repeating the IgG, and another six on repeating the subclasses. EPG on the 36 remaining samples showed no abnormalities in 22, polyclonal hypergammaglobulinaemia in seven, paraprotein in two, and a questionable band in five; seven of 36 had isolated increase in IgG4. We next examined bias in these assays, and retrospectively examined the specific effects of isolated IgG4 elevation. We performed mathematical simulations of over 3000 combinations of IgG subclass results, each subjected to 10,000 virtual nephelometric assays, to determine how frequently the 15% rule would be violated by random chance alone, as reflected by the co-efficient of variation. Our findings have very significant implications for the use of the IgG check in routine diagnostic IgG subclass estimation, and these will be presented.