High definition profiling of autoantibodies to glutamic acid decarboxylases GAD65/GAD67 in stiff-person syndrome.

Abstract:

:Highly reliable biomarkers for the diagnosis of neurological diseases are not widely available. Here we evaluated a luciferase immunoprecipitation technology (LIPS) for the diagnosis of a CNS autoimmune disorder, stiff-person syndrome (SPS). Analysis by LIPS of 40 sera samples from SPS and control subjects for anti-GAD65 antibodies revealed dramatic titer differences allowing diagnosis of SPS with 100% sensitivity and 100% specificity. Anti-GAD65 antibody titers of SPS were segregated from controls with values greater than 23 standard deviations above the control subject mean. By analyzing patient antibody responses directly to GAD65 sub-fragments, the central region containing the decarboxylase catalytic domain was highly immunoreactive with all of the SPS sera, while the N- and C-terminal regions showed lower antibody titers and only reacted with subsets of SPS sera. Additional profiling revealed that some SPS patients showed autoantibodies against GAD67 and tyrosine hydroxylase, but no significant immunoreactivity was detected with cysteine sulfinic acid decarboxylase or GABA transaminase. This study validates LIPS as a robust method to interrogate autoantibodies for the diagnosis of SPS and potentially other neurological diseases.

authors

Burbelo PD,Groot S,Dalakas MC,Iadarola MJ

doi

10.1016/j.bbrc.2007.11.077

subject

Has Abstract

pub_date

2008-02-01 00:00:00

pages

1-7

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(07)02397-2

journal_volume

366

pub_type

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