An animal uses only a small part of the immunological repertoire of the species in response to a given antigen (1-3). The most easy way to explain idiotypy is to assume that different somatic mutations have occurred in the germ-line V genes of different individuals. However recent data from this laboratory (4, 5) and from the Cazenave group (6) indicate that an individual normally expresses only a small fraction of its own immune repertoire and suggest that it is possible to make a given individual to synthesize an idiotype very similar to that of another individual.Normally rabbits, say, n ° 1 and n ° X, synthesize different idiotypes when injected with the same antigen. If rabbit X possesses in its immune repertoire silent lymphocytes precommitted for the synthesis of idiotype 1, it is reasonable to assume that their nonexpression is a result of specific suppressors which bear autoanti-idiotypic receptors (Ab2).l If we suppress the suppressor of clone 1 in rabbit X, by inducing an immune response against the suppressor (Ab2), we would expect to favour the synthesis of idiotype 1 in rabbit X. Using this rationale, anti-idiotypic antibodies (Ab2) were raised in allotype-matched rabbits, against a first antibody (Abl). These Ab2 were then injected into a third series of rabbits to obtain anti-anti-idiotypic antibodies (Ab3). These rabbits were then immunized with the original antigen. These experiments show clearly that the subsequent antibodies (Ab 1') display idiotypic specificities similar to those displayed by Ab 1.These results raise interesting questions, one of which concerns the idiotypic specificities of anti-anti-idiotypic antibodies (Ab3). Do Abl and Ab3 display similar idiotypic specificities? This paper presents a detailed idiotypic analysis of Ab3 in the Micrococcus lysodeikticus and in the tobacco mosaic virus (TMV) systems. The most salient features of our results are that Ab4 (specific antibodies to Ab3) recognize specifically Ab 1 and Ab 1'. Ab4 behaves as Ab2 and diversity does not increase along the chain of immunization.* Supported by a grant from the Belgian state.IRSIA Fellow. § Federation Nationale Researche Scientifique Fellow. ¶ Established Federation Nationale Researche Scientifique Investigator. 1 Abbreviations used in this paper: Abl, antibody raised against antigen; Ab2, anti-idiotypic antibody, Ab3, anti-anti-idiotypic antibody; Ab4, anti-anti-anti-idiotypic antibody; CIHO, anti-carbohydrate; Micrococcus, Micrococcus lysodeikticus; PBA, polyclonal B-cell activator; RNase, ribonuclease; TMV, tobacco mosaic virus. 184J. ExP, MEn.

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Autoantibodies to nuclear antigens, i.e. antinuclear antibodies (ANA), antibodies to double-stranded DNA (dsDNA) and extractable nuclear antigens (ENA), are useful as diagnostic markers for a variety of autoimmune diseases. In March 2010, the Belgian national External Quality Assessment Scheme sent a questionnaire on ANA, anti-dsDNA and anti-ENA antibody testing designed by the Dutch EASI (European Autoimmunity Standardization Initiative) team, to all clinical laboratories performing ANA testing. Virtually all laboratories completed the questionnaire (97·7%, 127/130). This paper discusses the results of this questionnaire and provides valuable information on the state-of-the-art of ANA, anti-dsDNA and anti-ENA antibody testing as practiced in the Belgian laboratories. In addition, this work presents practical recommendations developed by the members of the advisory board of the scheme as a result of the outcome of this study.

The Belgian national External Quality Assessment Scheme performed a nationwide survey using lyophilised plasma samples spiked with dabigatran or rivaroxaban to demonstrate to the Belgian clinical laboratories how these drugs affect their routine coagulation assays prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and antithrombin. Virtually all Belgian laboratories performing routine coagulation testing (189/192) participated in the survey. Both, dabigatran and rivaroxaban significantly prolonged the PT and aPTT in a concentration- and reagent-dependent manner. PT reagents were more influenced by rivaroxaban than by dabigatran and aPTT reagents more influenced by dabigatran than by rivaroxaban. Among PT reagents, Neoplastin R® was the most sensitive to rivaroxaban and Innovin® and Thromborel S® the least sensitive. Converting PT results to INR only increased the variability between reagents. Among aPTT reagents, Actin FSL® was the least sensitive to dabigatran while the other aPTT reagents showed slightly higher sensitivities. The presence of dabigatran led to falsely reduced fibrinogen concentrations when measured with a low thrombin concentration reagent. The presence of dabigatran caused an overestimation of the antithrombin level when measured with a thrombin-based activity assay and the presence of rivaroxaban an overestimation of the antithrombin level when measured with a FXa-based assay. Instrument-related differences were found for all tested parameters. In conclusion, this paper provides detailed information on the effect of dabigatran and rivaroxaban on routine coagulation assays as performed with a large number of reagent/instrument combinations.

BACKGROUND:As a cornerstone of quality management in the laboratory, External Quality Assessment (EQA) schemes are used to assess laboratory and analytical method performance. The characteristic function is used to describe the relation between the target concentration and the EQA standard deviation, which is an essential part of the evaluation process. The characteristic function is also used to compare the variability of different analytical methods.