Any level of elevated buy MK-8669 MCT may be a falsely elevated, even very high MCT: three samples with very high IgM RF values were reduced by 17 to 39% following HBT treatment. The MCT levels became normal in all three (41·8 to 2·6 µg/l; 160 to 5·2 µg/l; 200 to 4·1 µg/l) with 94%, 97% and 98% reduction, respectively. These patients had diagnoses of rheumatoid arthritis in the first two cases and non-Hodgkin lymphoma in the latter, respectively; none had any clinical history of mast cell increase or activation. Another sample with a raised RF (in

a patient with rheumatoid arthritis) had a 47% reduction in MCT (13·9 to 7·3 µg/l). Overall, there was no clear correlation between the measured IgM RF levels and the degree of reduction in MCT. This is due probably to variability in binding of mouse IgG Fc or AZD9291 supplier to the variability in the relative total amounts of IgG RF and IgA RF in individual sera (which are not measured in the IgM RF assay). HAMA interference can

also occur in the absence of RF but appears uncommon: one sample (systemic mastocytosis) with significantly raised tryptase level (319 µg/l) had almost undetectable levels of RF but raised levels of IgG HAMA (A450 0·115). Following blocking treatment, the tryptase result remained elevated (246 µg/l) but reduced by more than 17%, but the IgG HAMA dropped to normal levels (A450 0·087). Nine of 13 samples with a >17%

reduction in tryptase after HBT absorption had positive HAMA (A450 > 0·095) and eight of these became negative for HAMA after HBT treatment (one sample insufficient for HBT treatment) (Table 1). Heterophile antibodies can also lead potentially to false negative results, but we found little evidence for this in our cohort. In one RF-negative sample there was an apparent increase in MCT level >17% after HBT treatment (18·8 to 22·2 µg/l). In two RF-positive samples GNA12 analysed, there was an apparent increase in MCT following HBT treatment (43·3 to 49·2 and 128 to 143 µg/l), 14% and 12%, respectively. Both samples showed a decrease in RF level (314 to 102 and 129 to 82). HAMA was not detected in the first of these samples and there was insufficient material to measure HAMA in the second sample. We needed to ensure that the apparent presence of IgM RF was not itself caused by HAMA. Of the 14 samples with raised IgM RF, 13 had sufficient serum remaining to allow the analysis of HAMA. Of these, three were negative for IgG HAMA with the remaining samples having very low levels (A450 values between 0·095 and 0·197), and the blocking experiments revealed no samples that appeared to have false positive RF levels due to HAMA (Table 1).