Highs and lows of coeliac screening.

Coeliac screening is one of the most frequently requested investigations in immunology laboratories. This study evaluates seven commercial anti-tissue transglutaminase (tTG) enzyme-linked immunosorbent assay (ELISA) kits across a varied population of 80 routine samples received for coeliac screening. This investigation assesses whether or not absorbance levels can be used to detect low serum IgA and whether or not raised IgA concentrations can interfere with IgA-tTG results. Sensitivity and specificity varied hugely and four out of the seven methods required cut-off value modification to attain 100% sensitivity with endomysial testing. Four of the seven kits identified low IgA samples with greater than 90% accuracy, but sensitivity dropped to 75% in others. All the kits were affected by raised serum IgA concentrations, leading to false-positive results. There was notable variation between the seven kits in respect of high IgA concentrations and positive IgA-tTG results, with concordance analysis indicating a weak linear relationship between IgA concentration and tTG value. This study concludes that there is significant variability between the commercial tTG assays in the diagnostic market. Laboratories should be aware of their kit's limitations and may need to adjust cut-off values to maximise sensitivity. It is possible to identify IgA deficiency from the tTG values, but the ability to do this varies between manufacturers. Raised IgA levels continue to affect the specificity of IgA-tTG assays and interference by polyclonal and monoclonal IgA should be considered in samples with positive tTG and negative endomysial results.

Susceptibility to basal cell carcinoma: associations with PTCH polymorphisms.

Loss of function of the human patched gene (PTCH) is common and critical in basal cell carcinoma (BCC) development. Indirect evidence suggests polymorphism in PTCH mediates BCC risk. We studied 659 BCC cases and 300 controls to determine if exon 2(318), 3(429), 11(1552), 12(1665), 12(1686), 14(2199) and 23(3944) and intron 9(1336-135) and 15(2560+9)PTCH variants were sufficiently common for use in case-control studies, and if selected markers were associated with risk. Intron 15(2560+9) and exon 23(3944) variants were studied further. Their genotype frequencies were not significantly different in controls and cases, though frequency of the G(2560+9)-C(3944) haplotype was lower in all cases (odds ratio=0.44, p=0.009) and those stratified by BCC site and rate of development of further tumours. This association was not mediated by the extent of UVR exposure. We confirmed the robustness of these findings by showing these associations demonstrated similar odds ratios in two groups of randomly selected cases and controls, and using the false positive report probability (FPRP) approach described by Wacholder et al. (2004). The FPRP value (0.168) was in the noteworthy category. These data, showing for the first time that PTCH polymorphism mediates susceptibility, are compatible with reports showing that PTCH haploinsufficiency influences development of BCC precursor lesions.