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Letters to the Editor |
1 Laboratory of Neuroimmunology, Istituto di Ricovero e Cura a Carattere Scientifico, Neurological Institute "C. Mondino", University of Pavia, Pavia, Italy
2 Department of Medical and Work Sciences, University of Foggia, Foggia, Italy
3 Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy
aAddress correspondence to this author at: Foundation "Neurological Institute C. Mondino", via Mondino 2, I-27100 Pavia, Italy. Fax 39-0382-380286; e-mail diego.franciotta{at}mondino.it.
To the Editor:
The respective patterns of cerebrospinal fluid (CSF)-restricted oligoclonal IgG bands (OCBs) and assessment of their similarity in serum and CSF are important laboratory tools for evaluating immune-mediated inflammation of the central nervous system. OCB detection is the diagnostic laboratory tool of choice for multiple sclerosis (MS), in the initial, clinically isolated syndromes as well as in the primary progressive forms (1). The imperatives of diagnostic certainty and therapeutic timeliness have made this laboratory test mandatory.
Isoelectric focusing (IEF) with IgG immunodetection is the recommended technique for OCB measurements (1)(2). Many factors (e.g., variability in gel conductivity, quality of carrier ampholytes, and electroendosmosis) make IEF inherently difficult to standardize. Notwithstanding this shortcoming, the results of previously published studies on interlaboratory variability in OCB detection indicate acceptable reproducibility in IEF interpretations relative to absence vs presence of OCBs (3)(4). However, no study on OCB-positive samples has addressed IEF reproducibility on the basis of the number of bands. Nevertheless, associations of CSF OCB counts with MS prognosis (5) and with MS vs other inflammatory/infectious neurologic diseases (6) have been reported. We tested the interlaboratory reproducibility in OCB analysis on the occasion of the first OCB Quality Control survey by the Italian Association for Neuroimmunology.
We asked the 11 laboratories participating to analyze the control samples, to interpret IEF results in accordance with consensus patterns (2), and to report the number of bands observed. The controls consisted of aliquots of freshly collected CSF/serum samples from (a) a patient with suspected MS and high quantitatively detected IgG synthesis (sample A), (b) a patient with monoclonal gammopathy (diluted serum; sample B), and (c) a patient with Parkinson disease (sample C). The IgG concentrations in the samples were provided. All participants [mean (SE) number of CSF examinations/year, 485 (110)] used IEF [home-made gels, n = 4 laboratories; commercial gels (Helena or Amersham), n = 7 laboratories] with immunoblotting for IgG (2).
All participants identified samples A and C, respectively, as OCB-positive and OCB-negative. Nine of the 11 participants recognized monoclonal gammopathy in sample B. Fig. 1
shows how frequently the band counts in samples A and B were discordant among laboratories, including for sample B, which should have given sharp and easily countable monoclonal IgG bands.
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Our results confirm that the between-laboratory reproducibility for absence vs presence of OCBs is good and that monoclonal IgG bands may be misinterpreted as OCBs despite their typical ladder-like appearance in IEF (3)(4).
Band counting in IEF has never been standardized. Consequently, correlations between clinical aspects of neurologic diseases, particularly MS, and the number of bands (5)(6) have had only limited, at best "local", value. Our data show that band counts are not necessarily reproducible among laboratories.
Single bands on IEF have been detected with increasing frequency in recent years; such bands possibly indicate intrathecal IgG synthesis (7) and frequently are associated with MS (8). The present data suggest that the lack of reproducibility in band counting among laboratories does not affect the qualitative (i.e., absence vs presence) reporting of OCBs when three or more bands are present in the CSF sample, but that it could pose problems in the case of one or two bands. This possibility should be taken into account in both routine and research settings. External quality-control schemes for OCBs consequently should include samples with one or two bands to test laboratory performance in "critical" samples.
Acknowledgments
We thank the participants in the Italian Association for Neuroimmunology (AINI) survey, whose names can be found at www.aini.it.
References
The following articles in journals at HighWire Press have cited this article:
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  D. Franciotta and F. Lolli Interlaboratory Reproducibility of Isoelectric Focusing in Oligoclonal Band Detection Clin. Chem., August 1, 2007; 53(8): 1557 - 1558. [Full Text] [PDF]
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