M Auer1, H Hegen1, A Zeileis2, F Deisenhammer1. 1. Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. 2. Department of Statistics, Faculty of Economics and Statistics, University Innsbruck, Innsbruck, Austria.
Abstract
BACKGROUND AND PURPOSE: Intrathecal immunoglobulin (Ig) synthesis occurs in various chronic inflammatory neurological diseases. Different formulae have been developed for quantitative determination of Ig synthesis within the cerebrospinal fluid (CSF) compartment. The hyperbolic formula of Reiber is frequently used which, however, returns a considerable number of false positive results in empirical observations. METHODS: A computerized database of more than 19 000 paired CSF and serum samples was screened for patients presumed negative for local Ig synthesis and a new formula characterizing this collective was calculated. The validity of this formula was confirmed by several validation steps. RESULTS: A cohort of 1173 patients with normal CSF findings was used for quantile regression. The 97.5th quantile of the formula Qlim(IgX)=a×Qalbb was considered as the cut-off curve for intrathecal Ig synthesis using different constants a and b for IgG, IgA and IgM. Compared to the Reiber formula, a lower level of false positive results was produced especially for IgM and IgA which was confirmed in a separate clinically well defined validation cohort. In 77 patients with discrepant findings between Reiber and our formula no specific diagnoses were found confirming the low diagnostic value of borderline Ig synthesis. CONCLUSIONS: A new approximation formula was developed for determination of intrathecal Ig synthesis which produces fewer false positive results without reducing diagnostic sensitivity.
BACKGROUND AND PURPOSE: Intrathecal immunoglobulin (Ig) synthesis occurs in various chronic inflammatory neurological diseases. Different formulae have been developed for quantitative determination of Ig synthesis within the cerebrospinal fluid (CSF) compartment. The hyperbolic formula of Reiber is frequently used which, however, returns a considerable number of false positive results in empirical observations. METHODS: A computerized database of more than 19 000 paired CSF and serum samples was screened for patients presumed negative for local Ig synthesis and a new formula characterizing this collective was calculated. The validity of this formula was confirmed by several validation steps. RESULTS: A cohort of 1173 patients with normal CSF findings was used for quantile regression. The 97.5th quantile of the formula Qlim(IgX)=a×Qalbb was considered as the cut-off curve for intrathecal Ig synthesis using different constants a and b for IgG, IgA and IgM. Compared to the Reiber formula, a lower level of false positive results was produced especially for IgM and IgA which was confirmed in a separate clinically well defined validation cohort. In 77 patients with discrepant findings between Reiber and our formula no specific diagnoses were found confirming the low diagnostic value of borderline Ig synthesis. CONCLUSIONS: A new approximation formula was developed for determination of intrathecal Ig synthesis which produces fewer false positive results without reducing diagnostic sensitivity.
Authors: Marc Dürr; Gunnar Nissen; Kurt-Wolfram Sühs; Philipp Schwenkenbecher; Christian Geis; Marius Ringelstein; Hans-Peter Hartung; Manuel A Friese; Max Kaufmann; Michael P Malter; Marie Madlener; Franziska S Thaler; Tania Kümpfel; Makbule Senel; Martin G Häusler; Hauke Schneider; Florian Then Bergh; Christoph Kellinghaus; Uwe K Zettl; Klaus-Peter Wandinger; Nico Melzer; Catharina C Gross; Peter Lange; Jens Dreyhaupt; Hayrettin Tumani; Frank Leypoldt; Jan Lewerenz Journal: Neurol Neuroimmunol Neuroinflamm Date: 2021-10-25
Authors: Sergio M De Almeida; Indianara Rotta; Bin Tang; Florin Vaida; Scott Letendre; Ronald J Ellis Journal: J Neuroimmunol Date: 2021-03-08 Impact factor: 3.221
Authors: Franziska Di Pauli; Paul Morschewsky; Klaus Berek; Michael Auer; Angelika Bauer; Thomas Berger; Gabriel Bsteh; Paul Rhomberg; Kathrin Schanda; Anne Zinganell; Florian Deisenhammer; Markus Reindl; Harald Hegen Journal: Front Immunol Date: 2021-10-19 Impact factor: 7.561
Authors: Igal Rosenstein; Sofia Rasch; Markus Axelsson; Lenka Novakova; Kaj Blennow; Henrik Zetterberg; Jan Lycke Journal: Front Immunol Date: 2022-08-10 Impact factor: 8.786
Authors: Klaus Berek; Gabriel Bsteh; Michael Auer; Franziska Di Pauli; Anne Zinganell; Thomas Berger; Florian Deisenhammer; Harald Hegen Journal: Front Immunol Date: 2021-06-17 Impact factor: 7.561
Authors: Klaus Berek; Gabriel Bsteh; Michael Auer; Franziska Di Pauli; Astrid Grams; Dejan Milosavljevic; Paulina Poskaite; Christine Schnabl; Sebastian Wurth; Anne Zinganell; Thomas Berger; Janette Walde; Florian Deisenhammer; Harald Hegen Journal: Neurol Neuroimmunol Neuroinflamm Date: 2021-05-28