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000280960 1001_ $$0P:(DE-2719)2811468$$aKreye, Jakob$$b0$$eFirst author$$udzne
000280960 245__ $$aSpecific viral antibodies associate with anti-NMDAR encephalitis after herpes simplex encephalitis.
000280960 260__ $$aOrlando, Fla. [u.a.]$$bElsevier$$c2025
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000280960 520__ $$aHerpes simplex encephalitis (HSE) patients may develop secondary anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis (NMDARE), associated with worsened long-term neurological outcome. Immunosuppressive treatment can limit NMDAR autoantibody-mediated pathology, but early predictive biomarkers for the risk of NMDARE are lacking. In a multicenter study, we performed unbiased antibody reactome profiling using Phage ImmunoPrecipitation Sequencing (PhIP-Seq). HSE patients with secondary NMDARE (n = 13) versus those without (n = 10) showed enhanced antibody responses against HSV-1, but not HSV-2, which comprised specific antibodies to five peptides of the HSV-1 UL42 and UL48 proteins. A score of these signature CSF antibodies identified HSE patients with secondary NMDARE with a sensitivity of 75%, a specificity of > 99%, a positive predictive value of 90%, a negative predictive value of > 97% and an odds ratio (OR) of 209 (CI: 28 - 1,582) across all individuals in this study, and with similar performance values in serum (>66%, >99%, >88%, >96%, OR 307 (15 - 6,089)). These signature antibodies represent a promising biomarker to identify HSE patients at risk for NMDARE development. In NMDARE patients without a history of HSE and in MS patients, no disease-associated HSV antibody reactivity patterns were detected. Furthermore, we introduced the Multiplexed Index Calculations of the Antibody Reactome (MICAR) metric to characterize proteomic targets of compartment-specific antibody responses, an approach that is applicable in neuroimmunology and other compartmentalized disease states.
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000280960 650_7 $$2Other$$aAntibody reactome
000280960 650_7 $$2Other$$aEncephalitis
000280960 650_7 $$2Other$$aHSE
000280960 650_7 $$2Other$$aHSV
000280960 650_7 $$2Other$$aIntrathecal synthesis
000280960 650_7 $$2Other$$aMICAR
000280960 650_7 $$2Other$$aNMDAR
000280960 650_7 $$2Other$$aPhIP-Seq
000280960 7001_ $$aMorgenlander, William R$$b1
000280960 7001_ $$aThakar, Manjusha$$b2
000280960 7001_ $$aSchulte-Frankenfeld, Poul M$$b3
000280960 7001_ $$aSchott, Sarah$$b4
000280960 7001_ $$aBünger, Isabel$$b5
000280960 7001_ $$0P:(DE-2719)2811900$$aKornau, Hans-Christian$$b6$$udzne
000280960 7001_ $$aAngkeow, Julia W$$b7
000280960 7001_ $$aJayaraman, Sahana$$b8
000280960 7001_ $$aOtto, Carolin$$b9
000280960 7001_ $$aHahn, Wiebke$$b10
000280960 7001_ $$aLewerenz, Jan$$b11
000280960 7001_ $$aThaler, Franziska S$$b12
000280960 7001_ $$aKorporal-Kuhnke, Mirjam$$b13
000280960 7001_ $$aMelzer, Nico$$b14
000280960 7001_ $$aDargvainiene, Justina$$b15
000280960 7001_ $$aBien, Christian G$$b16
000280960 7001_ $$aKohlie, Rose$$b17
000280960 7001_ $$aLattwein, Erik$$b18
000280960 7001_ $$0P:(DE-2719)2810725$$aSchmitz, Dietmar$$b19$$udzne
000280960 7001_ $$aCalabresi, Peter A$$b20
000280960 7001_ $$aPardo, Carlos A$$b21
000280960 7001_ $$0P:(DE-2719)2810931$$aPrüss, Harald$$b22$$udzne
000280960 7001_ $$aRuprecht, Klemens$$b23
000280960 7001_ $$aBenjamin Larman, H.$$b24
000280960 773__ $$0PERI:(DE-600)1462491-6$$a10.1016/j.bbi.2025.106073$$gVol. 130, p. 106073 -$$p106073$$tBrain, behavior and immunity$$v130$$x0889-1591$$y2025
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