TY - JOUR
T1 - Implementation of National Institute for Health and Care Excellence (NICE) guidance to measure IgA with all coeliac screens: can an affordable solution be devised?
T2 - IgA measurement in coeliac serological screening
AU - Mac Lochlainn, D. J.
AU - Hira-Kazal, R.
AU - Varney, H.
AU - Maher, J.
PY - 2017/5/19
Y1 - 2017/5/19
N2 - There has been a dramatic increase in requests for coeliac disease (CD) serological
screening using IgA tissue transglutaminase antibodies (IgA-tTG). Recently, the UK
National Institute for Health and Care Excellence has revised its guidance,
recommending that total IgA should also be measured in all samples. This is justified
since false negative results may occur with IgA deficiency. However, implementation of
this guidance will incur considerable expense. Tests that measure IgA-tTG antibodies
can detect IgA deficiency, indicated by low background signal. This provides an
opportunity to identify samples containing IgA<0.2g/L, obviating the need for
unselected IgA measurement. We investigated feasibility of this approach in two centres that use the EliA™ Celikey™ assay or QUANTA Lite® ELISA to quantify IgA-tTG
antibodies. In both cases, total IgA correlated strongly with background IgA-tTG assay
signal. Using the Celikey™ assay, a threshold of <17.5 response units achieved 100%
sensitivity (95% confidence intervals 79.4% - 100%) for detection of IgA<0.2g/L,
circumventing the need for IgA testing in >99% of sera. A similar principle was
demonstrated for the QUANTA Lite® assay, whereby a threshold optical density of
<0.0265 also achieved 100% sensitivity (95% confidence intervals 78.2% - 100%) for
IgA<0.2g/L, avoiding unnecessary IgA testing in 67% of cases. These data suggest that
CD screening tests can reliably identify samples containing low IgA in a real-life
setting, obviating the need for blanket testing. However, this approach requires careful
individualized validation, given the divergent efficiency with which assays identify
samples containing low IgA.
AB - There has been a dramatic increase in requests for coeliac disease (CD) serological
screening using IgA tissue transglutaminase antibodies (IgA-tTG). Recently, the UK
National Institute for Health and Care Excellence has revised its guidance,
recommending that total IgA should also be measured in all samples. This is justified
since false negative results may occur with IgA deficiency. However, implementation of
this guidance will incur considerable expense. Tests that measure IgA-tTG antibodies
can detect IgA deficiency, indicated by low background signal. This provides an
opportunity to identify samples containing IgA<0.2g/L, obviating the need for
unselected IgA measurement. We investigated feasibility of this approach in two centres that use the EliA™ Celikey™ assay or QUANTA Lite® ELISA to quantify IgA-tTG
antibodies. In both cases, total IgA correlated strongly with background IgA-tTG assay
signal. Using the Celikey™ assay, a threshold of <17.5 response units achieved 100%
sensitivity (95% confidence intervals 79.4% - 100%) for detection of IgA<0.2g/L,
circumventing the need for IgA testing in >99% of sera. A similar principle was
demonstrated for the QUANTA Lite® assay, whereby a threshold optical density of
<0.0265 also achieved 100% sensitivity (95% confidence intervals 78.2% - 100%) for
IgA<0.2g/L, avoiding unnecessary IgA testing in 67% of cases. These data suggest that
CD screening tests can reliably identify samples containing low IgA in a real-life
setting, obviating the need for blanket testing. However, this approach requires careful
individualized validation, given the divergent efficiency with which assays identify
samples containing low IgA.
U2 - 10.1111/cei.12982
DO - 10.1111/cei.12982
M3 - Article
SN - 0009-9104
JO - Clinical and Experimental Immunology
JF - Clinical and Experimental Immunology
ER -