New markers and an old phenomenon: prozone effect disturbing detection of filaggrin (keratin) autoantibodies

Dubois-Galopin, Frederique; Beauvillain, Céline; Dubois, Damien; Pillet, Anne; Rénier, Gilles; Jeannin, Pascale; Masson, Charles; Chevailler, Alain

doi:10.1136/ard.2006.066027

Cited by 10 publications

(8 citation statements)

References 10 publications

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“…A prozone effect in two‐step assays is therefore far less common but not excluded (Courtenay‐Luck et al ., ). Prozone effects are frequent in immunometric assays but were also observed in a variety of other immunoassays including malaria rapid diagnostic tests (Luchavez et al ., ) and immunohistochemistry (Dubois‐Galopin et al ., ). In the present article, all phenomena with increased reactivity after dilution of the sample will be referred to as prozone effect, independent of their mechanism.…”

Section: The Prozone Phenomenon and The Hook Effectmentioning

confidence: 97%

The complement‐mediated prozone effect in the Luminex single‐antigen bead assay and its impact on HLA antibody determination in patient sera

Weinstock

Schnaidt²

2012

Int J Immunogenetics

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The Luminex xMAP system has become an important tool for HLA antibody screening and identification in sera of transplant patients. Recently, the Luminex single antigen bead assay was shown to be prone to an artefact, the so called prozone phenomenon: Sera with high titer HLA antibodies gave negative results when tested neat, but reacted strongly positive after 1:10 dilution. We also observed such a phenomenon and found that it was most likely caused by the complement component 1 (C1) by competitively displacing the detection antibodies. In this article we review the complement-mediated prozone effect and other mechanisms of interference with solid phase assays, and we discuss possible consequences for HLA antibody testing with the Luminex SAB assay.

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Section: The Prozone Phenomenon and The Hook Effectmentioning

confidence: 97%

The complement‐mediated prozone effect in the Luminex single‐antigen bead assay and its impact on HLA antibody determination in patient sera

Weinstock

Schnaidt²

2012

Int J Immunogenetics

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“…While HDE is caused by a saturating excess in antigen concentration in ELISA, which prevents sandwich or bridge formation, the cause of HDE in IHC and ICC is less well understood. Among other explanations, it has been speculated that HDE in IIF might be caused by anti‐immunoglobulin conjugates being unable to reach their antigenic determinants on tightly clustered immunoglobulin molecules . Long et al did not find evidence for a prozone effect with the commercial CBA (Euroimmun) when re‐testing sera that were negative at 1:4 and the standard 1:10 dilution at 1:32 and 1:120 dilutions .…”

Section: Special Issuesmentioning

confidence: 99%

Aquaporin‐4 Antibodies (NMO‐IgG) as a Serological Marker of Neuromyelitis Optica: A Critical Review of the Literature

2013

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Antibodies to aquaporin-4 (called NMO-IgG or AQP4-Ab) constitute a sensitive and highly specific serum marker of neuromyelitis optica (NMO) that can facilitate the differential diagnosis of NMO and classic multiple sclerosis. NMO-IgG/AQP4-Ab seropositive status has also important prognostic and therapeutic implications in patients with isolated longitudinally extensive myelitis (LETM) or optic neuritis (ON). In this article, we comprehensively review and critically appraise the existing literature on NMO-IgG/AQP4-Ab testing. All available immunoassays-including tissue-based (IHC), cell-based (ICC, FACS) and protein-based (RIPA, FIPA, ELISA, Western blotting) assays-and their differential advantages and disadvantages are discussed. Estimates for sensitivity, specificity, and positive and negative likelihood ratios are calculated for all published studies and accuracies of the various immunoassay techniques compared. Subgroup analyses are provided for NMO, LETM and ON, for relapsing vs. monophasic disease, and for various control groups (eg, MS vs. other controls). Numerous aspects of NMO-IgG/AQP4-Ab testing relevant for clinicians (eg, impact of antibody titers and longitudinal testing, indications for repeat testing, relevance of CSF testing and subclass analysis, NMO-IgG/AQP4-Ab in patients with rheumatic diseases) as well as technical aspects (eg, AQP4-M1 vs. AQP4-M23-based assays, intact AQP4 vs. peptide substrates, effect of storage conditions and freeze/thaw cycles) and pitfalls are discussed. Finally, recommendations for the clinical application of NMO-IgG/ AQP4-Ab serology are given.

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“…Fifth, while the concept of “prozone” is generally thought of only in terms of in vivo or solution phenomena, this needs to be reconsidered and explored in the context of aab detection in both older and newer diagnostic platforms [ 79 , 80 ]. Not all diagnostic platforms have the same antigen density available for aab binding or the same dynamic range.…”

Section: Breaking Down Paradigmsmentioning

confidence: 99%

Toward a new autoantibody diagnostic orthodoxy: understanding the bad, good and indifferent

Fritzler

2012

Autoimmun Highlights

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Rapid advances in diagnostic technologies used to detect autoantibodies have made it difficult for even the most modern laboratory to keep abreast of the changing approaches and platforms, not to mention the clinicians who are hard pressed to keep abreast of evolving diagnostic paradigms attended by these newer techniques. While autoantibody testing is traditionally considered to be primarily serving the realm of diagnostic medicine, there is little doubt that autoantibodies are also being recognized as an approach to providing prognostic and therapeutic information. Accordingly, along with related proteomics, genomics and metabolomics, it is taking on increasing importance in the realm of personalized medicine. In today’s world of autoantibody diagnostics, overarching concerns about false-negative and false-positive autoantibodies tests cannot be summarily dismissed by citing pros or cons of any one technology or diagnostic platform, but often point to persisting gaps in our knowledge about, and understanding of, the origin and roles of autoantibodies. Before we can hope to completely understand the enigmas that attend the results of autoantibody diagnostic tests, perhaps it is time to step back and re-examine long-accepted paradigms and beliefs. This review will address some of the issues that impact on autoantibody detection technologies and some of the considerations and issues that will attend a new orthodoxy of autoantibody diagnostics. These issues will be addressed in the context of “bad” (pathogenic), “good” (protective) or “indifferent” (no apparent role in disease) autoantibodies.

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New markers and an old phenomenon: prozone effect disturbing detection of filaggrin (keratin) autoantibodies

Cited by 10 publications

References 10 publications

The complement‐mediated prozone effect in the Luminex single‐antigen bead assay and its impact on HLA antibody determination in patient sera

The complement‐mediated prozone effect in the Luminex single‐antigen bead assay and its impact on HLA antibody determination in patient sera

Aquaporin‐4 Antibodies (NMO‐IgG) as a Serological Marker of Neuromyelitis Optica: A Critical Review of the Literature

Toward a new autoantibody diagnostic orthodoxy: understanding the bad, good and indifferent

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