Implementation of National Institute for Health and Care Excellence (NICE) guidance to measure immunoglobulin A with all coeliac screens: can an affordable solution be devised?

There has been a dramatic increase in requests for coeliac disease (CD) serological screening using immunoglobulin (Ig)A 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, as 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 the feasibility of this approach in two centres that use the EliA™ Celikey™ assay or QUANTA Lite® enzyme-linked immunosorbent assay 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 ≤ 0·2 g/l, avoiding unnecessary IgA testing in 67% of cases. These data suggest that CD screening tests can identify samples reliably 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.

The efficacy and safety of rituximab in a chart review study of 15 patients with systemic lupus erythematosus.

In contrast to randomised clinical trials, open-label studies have suggested that B cell depletion by a course of rituximab is associated with a significant clinical benefit. Our aim was to assess the safety and efficacy of rituximab in 15 refractory lupus patients, particularly those with more than one course of therapy. Disease activity was measured by the classic British Isles Lupus Assessment Group (BILAG) index, anti-DNA antibodies and complement levels. We assessed immunoglobulin levels, functional antibodies and serious adverse events. The mean patient age ± SD was 37.9 ± 7.2 years and mean disease duration was 8.5 ± 3.3 years; 46% were Afro-Caribbean, 27% South Asian, 20% Caucasian and 7% others. Twelve patients responded by 6 months; six avoided major flare for >1 year. Complete absence of disease activity (BILAG D/E) lasted for 5.5 (SD 3.8) months and 4.8 (SD 3.6) months after the first (n = 15) and second (n = 9) rituximab course, respectively. The mean 6-month reduction in daily prednisolone was 10.4 (SD 11.4) mg/day and 10.7 (SD 9.3) mg/day from baseline after the first and second course, respectively. Patients with low C3/C4 normalised their C3 by 6 months. Most patients with raised anti-dsDNA normalised after rituximab courses. Serious adverse events only occurred after more than four courses of rituximab. Rituximab was safe and efficacious for treating patients with refractory systemic lupus erythematosus (SLE) and was associated with significant steroid reduction, but more than four courses of rituximab was associated with an increased risk of serious infection in two patients.

How should a district general hospital immunology service screen for anti-nuclear antibodies? An 'in-the-field' audit.

Anti-nuclear antibody (ANA) testing assists in the diagnosis of several immune-mediated disorders. The gold standard method for detection of these antibodies is by indirect immunofluorescence testing on human epidermoid laryngeal carcinoma (HEp-2) cells. However, many laboratories test for these antibodies using solid-phase assays such as enzyme-linked immunosorbent assay (ELISA), which allows for higher throughput testing at reduced cost. In this study, we have audited the performance of a previously established ELISA assay to screen for ANA, making comparison with the gold standard HEp-2 immunofluorescence test. A prospective and unselected sample of 89 consecutive ANA test requests by consultant rheumatologists were evaluated in parallel over a period of 10 months using both tests. ELISA and HEp-2 screening assays yielded 40 (45%) and 72 (81%) positive test results, respectively, demonstrating lack of concordance between test methods. Using standard and clinical samples, it was demonstrated that the ELISA method did not detect several ANA with nucleolar, homogeneous and speckled immunofluorescence patterns. None of these ELISA(NEG) HEp-2(POS) ANA were reactive with a panel of six extractable nuclear antigens or with double-stranded DNA. Nonetheless, 13 of these samples (15%) originated from patients with recognized ANA-associated disease (n = 7) or Raynaud's phenomenon (n = 6). We conclude that ELISA screening may fail to detect clinically relevant ANA that lack defined specificity for antigen.