BACKGROUND: Commercial assays measuring antibodies to citrullinated protein/peptide (ACPA) show poor quantitative agreement. The diagnostic industry has never adopted the International Union of Immunological Societies-Centers for Disease Control and Prevention (IUIS-CDC) ACPA reference standard. Recently, the National Institute for Biological Standards and Control (NIBSC) prepared a new candidate ACPA standard (18/204). We evaluated both reference materials using different commercially available ACPA assays.
METHODS: This is an international study in which the NIBSC candidate ACPA standard and the IUIS-CDC ACPA reference material were analysed together with 398 diagnostic samples from individuals with rheumatoid arthritis (RA) and in 1073 individuals who did not have RA using nine commercial ACPA assays.
RESULTS: For both reference materials and samples from individuals with RA and individuals who did not have RA, there were large differences in quantitative ACPA results between assays. For most assays, values for the IUIS-CDC standard were lower than values for NIBSC 18/204 and the IUIS-CDC/NIBSC ratio was comparable for several, but not all assays. When NIBSC 18/204 was used as a calibrator, an improvement in alignment of ACPA results across several of the evaluated assays was obtained. Moreover, NIBSC 18/204 could align clinical interpretation for some but not all assays.
CONCLUSIONS: Adoption of an international standard for ACPA determination is highly desirable. The candidate NIBSC 18/204 standard improved the standardisation and alignment of most ACPA assays and might therefore be recommended to be used as reference in commercial assays.

Recent reports of severe haemolytic reactions upon high dose treatment with new generation intravenous immunoglobulins (IVIGs) prompted us to examine the anti-A and anti-B haemagglutinin content of these therapeutics. We compared four different test methods, namely the indirect and direct haemagglutination test as described in the European Pharmacopoiea (Ph. Eur.) and two commercial gelcard systems with the aim to define the most reliable method for a large-scale comparison of different IVIG products. Absolute titres varied when the same samples were analyzed by the four methods, while the relative ranking of six different IVIG preparations representing different manufacturing classes was identical. New generation IVIGs showed 1-2 titre steps higher anti-A titres than the older products. Haemagglutinin titres of all 48 IVIG batches analyzed were within the current Ph. Eur. specification of ≤1:64 when tested by the official pharmacopoeial method. Based on efficiency, reliability and lower costs, the direct gelcard method could be a valid alternative to the official Ph. Eur. method to serve as a limit test. However, due to the highest intermediate precision, the official Ph. Eur. method seems to be most suitable to compare haemagglutinin titres of different IVIG products.

BACKGROUND: The Elecsys® HIV combi PT assay was developed to allow earlier detection of HIV infection with increased sensitivity and specificity.
OBJECTIVE: To validate the assay for screening and reliable early detection of HIV-1 infection in Asia.
METHODS: Samples tested reflected those routinely screened in Asia and comprised: HIV-1 antigen lysate (25 samples) and antibody (20 samples) dilutions; seven HIV-1 seroconversion panels (46 samples); 39 patient samples from early infection; 183 known-positive sera; HIV-1 p24 antigen sensitivity panel (seven samples); >500 routine clinical samples per center. The Elecsys® HIV combi PT assay was compared with fourth- (ADVIA Centaur® HIV combo, ARCHITECT® HIV combo, Elecsys® HIV combi) and third-generation (VIRONOSTIKA® HIV Uni-Form II Plus O, Zhuhai Livzon Anti-HIV EIA, Serodia® Particle Agglutination) assays commonly used in the region.
RESULTS: Overall, the Elecsys® HIV combi PT showed superior or similar sensitivity to the comparators for detecting all subtypes. The assay correctly identified all positive samples, including those taken soon after infection, and detected seroconversion at a similar or shorter time interval than the comparators. The analytical sensitivity of Elecsys® HIV combi PT for HIV-1 p24 antigen was 0.90 IU/mL, which was lower than reported previously. The assay showed good specificity (99.86%) that was superior or equivalent to the other fourth-generation assays tested.
CONCLUSIONS: These robust data demonstrate the good subtype inclusivity of the Elecsys® HIV combi PT assay and its suitability for screening and reliable early detection of HIV infection in Asia.