Background
IgG4 disease can have apparently “normal” levels of IgG4 due to antigen
excess conditions. IgG4 measurement therefore appears falsely low. UK
NEQAS data and other reports have suggested this problem occurred despite
pre-existing antigen excess detection steps.
Methods
We examined the prevalence and characteristics of prozoning in our
laboratory and patient cohorts, to determine the clinical relevance of the
problem.
Results
We establish that the prevalence of raised IgG4 in routine IgG4 analysis is low
(<1%) using one of the 2 routine methods in use in the UK. We show that
subsequent assay modification appears to have reduced the likelihood of
misleading readings. However, the original version of the assay prozoned to
low levels (below 0.64g/L) in 41% of high IgG4 samples in our patients. This
may explain the previous reports of low sensitivity of raised IgG4 for IgG4RD,
and predictive values should be re-evaluated in this disease using modified
prozone-resistant protocols.
Conclusions
All laboratories providing IgG4 measurements should verify that their assays
are fit for the clinical quality requirement of detection raised IgG4 levels and
must verify the upper limit of their reference ranges and freedom from
prozoning
