Anti-dopamine D2 receptor antibodies in chronic tic disorders

Francesco Addabbo; Valentina Baglioni; Anette Schrag; Markus J. Schwarz; Andrea Dietrich; Pieter J. Hoekstra; Davide Martino; Maura Buttiglione; Zacharias Anastasiou; Alan Apter; Juliane Ball; Erika Bartolini; Noa Benaroya-Milshtein; Benjamin Bodmer; Emese Bognar; Bianka Burger; Judith Buse; Francesco Cardona; Marta Correa Vela; Roberta Creti; Nanette M. Debes; Androulla Efstratiou; Maria Cristina Ferro; Carolin Fremer; Blanca Garcia-Delgar; Maria Gariup; Marianthi Georgitsi; Mariangela Gulisano; Annelieke Hagen; Julie Hagstrøm; Tammy J. Hedderly; Isobel Heyman; Chaim Huyser; Monica Imperi; Iordanis Karagiannidis; Giovanni Laviola; Simone Macri; Marcos Madruga-Garrido; Immaculada Margarit; Anna Marotta; Ute C. Meier; Pablo Mir; Natalie Moll; Astrid Morer; Kirsten Müller-Vahl; Alexander Münchau; Peter Nagy; Valeria Neri; Thaïra J.C. Openneer; Graziella Orefici; Peristera Paschou; Angela Periañez; Vasco Alessandra Pellico; Onofrio Petruzzelli; Kerstin Plessen; Cesare Porcelli; Marina Redondo; Renata Rizzo; Paolo Roazzi; Veit Roessner; Daphna Ruhrman; Jaana M.L. Schnell; Gregor A. Schütze; Paola Rosaria Silvestri; Liselotte Skov; Tamar Steinberg; Sara Stöber; Marco Tallon; Friederike Tagwerker Gloor; Susanne Walitza; Jennifer Tübing; Victoria Turner; Elif Weidinger; Zsanett Tarnok

doi:10.1111/dmcn.14613

Anti-dopamine D2 receptor antibodies in chronic tic disorders

Francesco Addabbo, Valentina Baglioni, Anette Schrag, Markus J. Schwarz, Andrea Dietrich, Pieter J. Hoekstra, Davide Martino, Maura Buttiglione^*, Zacharias Anastasiou, Alan Apter, Juliane Ball, Erika Bartolini, Noa Benaroya-Milshtein, Benjamin Bodmer, Emese Bognar, Bianka Burger, Judith Buse, Francesco Cardona, Marta Correa Vela, Roberta CretiNanette M. Debes, Androulla Efstratiou, Maria Cristina Ferro, Carolin Fremer, Blanca Garcia-Delgar, Maria Gariup, Marianthi Georgitsi, Mariangela Gulisano, Annelieke Hagen, Julie Hagstrøm, Tammy J. Hedderly, Isobel Heyman, Chaim Huyser, Monica Imperi, Iordanis Karagiannidis, Giovanni Laviola, Simone Macri, Marcos Madruga-Garrido, Immaculada Margarit, Anna Marotta, Ute C. Meier, Pablo Mir, Natalie Moll, Astrid Morer, Kirsten Müller-Vahl, Alexander Münchau, Peter Nagy, Valeria Neri, Thaïra J.C. Openneer, Graziella Orefici, Peristera Paschou, Angela Periañez, Vasco Alessandra Pellico, Onofrio Petruzzelli, Kerstin Plessen, Cesare Porcelli, Marina Redondo, Renata Rizzo, Paolo Roazzi, Veit Roessner, Daphna Ruhrman, Jaana M.L. Schnell, Gregor A. Schütze, Paola Rosaria Silvestri, Liselotte Skov, Tamar Steinberg, Sara Stöber, Marco Tallon, Friederike Tagwerker Gloor, Susanne Walitza, Jennifer Tübing, Victoria Turner, Elif Weidinger, Zsanett Tarnok

^*Corresponding author for this work

2 Citations (Scopus)

Abstract

Aim: To investigate the association between circulating anti-dopamine D2 receptor (D2R) autoantibodies and the exacerbation of tics in children with chronic tic disorders (CTDs). Method: One hundred and thirty-seven children with CTDs (108 males, 29 females; mean age [SD] 10y 0mo [2y 7mo], range 4–16y) were recruited over 18 months. Patients were assessed at baseline, at tic exacerbation, and at 2 months after exacerbation. Serum anti-D2R antibodies were evaluated using a cell-based assay and blinded immunofluorescence microscopy scoring was performed by two raters. The association between visit type and presence of anti-D2R antibodies was measured with McNemar’s test and repeated-measure logistic regression models, adjusting for potential demographic and clinical confounders. Results: At exacerbation, 11 (8%) participants became anti-D2R-positive (‘early peri-exacerbation seroconverters’), and nine (6.6%) became anti-D2R-positive at post-exacerbation (‘late peri-exacerbation seroconverters’). The anti-D2R antibodies were significantly associated with exacerbations when compared to baseline (McNemar’s odds ratio=11, p=0.003) and conditional logistic regression confirmed this association (Z=3.49, p<0.001) after adjustment for demographic and clinical data and use of psychotropic drugs. Interpretation: There is a potential association between immune mechanisms and the severity course of tics in adolescents with CTDs.

Original language	English
Journal	Developmental Medicine and Child Neurology
Volume	62
Issue number	10
Pages (from-to)	1205-1212
Number of pages	8
ISSN	0012-1622
DOIs	https://doi.org/10.1111/dmcn.14613
Publication status	Published - 01.10.2020

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Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

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10.1111/dmcn.14613

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Addabbo, F., Baglioni, V., Schrag, A., Schwarz, M. J., Dietrich, A., Hoekstra, P. J., Martino, D., Buttiglione, M., Anastasiou, Z., Apter, A., Ball, J., Bartolini, E., Benaroya-Milshtein, N., Bodmer, B., Bognar, E., Burger, B., Buse, J., Cardona, F., Correa Vela, M., ... Tarnok, Z. (2020). Anti-dopamine D2 receptor antibodies in chronic tic disorders. Developmental Medicine and Child Neurology, 62(10), 1205-1212. https://doi.org/10.1111/dmcn.14613

@article{4245f1fea66b4e29b798a7fe2b4244a7,

title = "Anti-dopamine D2 receptor antibodies in chronic tic disorders",

abstract = "Aim: To investigate the association between circulating anti-dopamine D2 receptor (D2R) autoantibodies and the exacerbation of tics in children with chronic tic disorders (CTDs). Method: One hundred and thirty-seven children with CTDs (108 males, 29 females; mean age [SD] 10y 0mo [2y 7mo], range 4–16y) were recruited over 18 months. Patients were assessed at baseline, at tic exacerbation, and at 2 months after exacerbation. Serum anti-D2R antibodies were evaluated using a cell-based assay and blinded immunofluorescence microscopy scoring was performed by two raters. The association between visit type and presence of anti-D2R antibodies was measured with McNemar{\textquoteright}s test and repeated-measure logistic regression models, adjusting for potential demographic and clinical confounders. Results: At exacerbation, 11 (8%) participants became anti-D2R-positive ({\textquoteleft}early peri-exacerbation seroconverters{\textquoteright}), and nine (6.6%) became anti-D2R-positive at post-exacerbation ({\textquoteleft}late peri-exacerbation seroconverters{\textquoteright}). The anti-D2R antibodies were significantly associated with exacerbations when compared to baseline (McNemar{\textquoteright}s odds ratio=11, p=0.003) and conditional logistic regression confirmed this association (Z=3.49, p<0.001) after adjustment for demographic and clinical data and use of psychotropic drugs. Interpretation: There is a potential association between immune mechanisms and the severity course of tics in adolescents with CTDs.",

author = "Francesco Addabbo and Valentina Baglioni and Anette Schrag and Schwarz, {Markus J.} and Andrea Dietrich and Hoekstra, {Pieter J.} and Davide Martino and Maura Buttiglione and Zacharias Anastasiou and Alan Apter and Juliane Ball and Erika Bartolini and Noa Benaroya-Milshtein and Benjamin Bodmer and Emese Bognar and Bianka Burger and Judith Buse and Francesco Cardona and {Correa Vela}, Marta and Roberta Creti and Debes, {Nanette M.} and Androulla Efstratiou and Ferro, {Maria Cristina} and Carolin Fremer and Blanca Garcia-Delgar and Maria Gariup and Marianthi Georgitsi and Mariangela Gulisano and Annelieke Hagen and Julie Hagstr{\o}m and Hedderly, {Tammy J.} and Isobel Heyman and Chaim Huyser and Monica Imperi and Iordanis Karagiannidis and Giovanni Laviola and Simone Macri and Marcos Madruga-Garrido and Immaculada Margarit and Anna Marotta and Meier, {Ute C.} and Pablo Mir and Natalie Moll and Astrid Morer and Kirsten M{\"u}ller-Vahl and Alexander M{\"u}nchau and Peter Nagy and Valeria Neri and Openneer, {Tha{\"i}ra J.C.} and Graziella Orefici and Peristera Paschou and Angela Peria{\~n}ez and Pellico, {Vasco Alessandra} and Onofrio Petruzzelli and Kerstin Plessen and Cesare Porcelli and Marina Redondo and Renata Rizzo and Paolo Roazzi and Veit Roessner and Daphna Ruhrman and Schnell, {Jaana M.L.} and Sch{\"u}tze, {Gregor A.} and Silvestri, {Paola Rosaria} and Liselotte Skov and Tamar Steinberg and Sara St{\"o}ber and Marco Tallon and Gloor, {Friederike Tagwerker} and Susanne Walitza and Jennifer T{\"u}bing and Victoria Turner and Elif Weidinger and Zsanett Tarnok",

note = "Funding Information: The EMTICS project has received funding from the European Union{\textquoteright}s Seventh Framework Programme for research, technological development, and demonstration under Grant agreement No. 278367. The authors and EMTICS collaborators are grateful to all patients, their siblings, and parents who made this research possible. Publisher Copyright: {\textcopyright} 2020 Mac Keith Press Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2020",

month = oct,

day = "1",

doi = "10.1111/dmcn.14613",

language = "English",

volume = "62",

pages = "1205--1212",

journal = "Developmental Medicine and Child Neurology",

issn = "0012-1622",

number = "10",

}

Addabbo, F, Baglioni, V, Schrag, A, Schwarz, MJ, Dietrich, A, Hoekstra, PJ, Martino, D, Buttiglione, M, Anastasiou, Z, Apter, A, Ball, J, Bartolini, E, Benaroya-Milshtein, N, Bodmer, B, Bognar, E, Burger, B, Buse, J, Cardona, F, Correa Vela, M, Creti, R, Debes, NM, Efstratiou, A, Ferro, MC, Fremer, C, Garcia-Delgar, B, Gariup, M, Georgitsi, M, Gulisano, M, Hagen, A, Hagstrøm, J, Hedderly, TJ, Heyman, I, Huyser, C, Imperi, M, Karagiannidis, I, Laviola, G, Macri, S, Madruga-Garrido, M, Margarit, I, Marotta, A, Meier, UC, Mir, P, Moll, N, Morer, A, Müller-Vahl, K, Münchau, A, Nagy, P, Neri, V, Openneer, TJC, Orefici, G, Paschou, P, Periañez, A, Pellico, VA, Petruzzelli, O, Plessen, K, Porcelli, C, Redondo, M, Rizzo, R, Roazzi, P, Roessner, V, Ruhrman, D, Schnell, JML, Schütze, GA, Silvestri, PR, Skov, L, Steinberg, T, Stöber, S, Tallon, M, Gloor, FT, Walitza, S, Tübing, J, Turner, V, Weidinger, E & Tarnok, Z 2020, 'Anti-dopamine D2 receptor antibodies in chronic tic disorders', Developmental Medicine and Child Neurology, vol. 62, no. 10, pp. 1205-1212. https://doi.org/10.1111/dmcn.14613

TY - JOUR

T1 - Anti-dopamine D2 receptor antibodies in chronic tic disorders

AU - Addabbo, Francesco

AU - Baglioni, Valentina

AU - Schrag, Anette

AU - Schwarz, Markus J.

AU - Dietrich, Andrea

AU - Hoekstra, Pieter J.

AU - Martino, Davide

AU - Buttiglione, Maura

AU - Anastasiou, Zacharias

AU - Apter, Alan

AU - Ball, Juliane

AU - Bartolini, Erika

AU - Benaroya-Milshtein, Noa

AU - Bodmer, Benjamin

AU - Bognar, Emese

AU - Burger, Bianka

AU - Buse, Judith

AU - Cardona, Francesco

AU - Correa Vela, Marta

AU - Creti, Roberta

AU - Debes, Nanette M.

AU - Efstratiou, Androulla

AU - Ferro, Maria Cristina

AU - Fremer, Carolin

AU - Garcia-Delgar, Blanca

AU - Gariup, Maria

AU - Georgitsi, Marianthi

AU - Gulisano, Mariangela

AU - Hagen, Annelieke

AU - Hagstrøm, Julie

AU - Hedderly, Tammy J.

AU - Heyman, Isobel

AU - Huyser, Chaim

AU - Imperi, Monica

AU - Karagiannidis, Iordanis

AU - Laviola, Giovanni

AU - Macri, Simone

AU - Madruga-Garrido, Marcos

AU - Margarit, Immaculada

AU - Marotta, Anna

AU - Meier, Ute C.

AU - Mir, Pablo

AU - Moll, Natalie

AU - Morer, Astrid

AU - Müller-Vahl, Kirsten

AU - Münchau, Alexander

AU - Nagy, Peter

AU - Neri, Valeria

AU - Openneer, Thaïra J.C.

AU - Orefici, Graziella

AU - Paschou, Peristera

AU - Periañez, Angela

AU - Pellico, Vasco Alessandra

AU - Petruzzelli, Onofrio

AU - Plessen, Kerstin

AU - Porcelli, Cesare

AU - Redondo, Marina

AU - Rizzo, Renata

AU - Roazzi, Paolo

AU - Roessner, Veit

AU - Ruhrman, Daphna

AU - Schnell, Jaana M.L.

AU - Schütze, Gregor A.

AU - Silvestri, Paola Rosaria

AU - Skov, Liselotte

AU - Steinberg, Tamar

AU - Stöber, Sara

AU - Tallon, Marco

AU - Gloor, Friederike Tagwerker

AU - Walitza, Susanne

AU - Tübing, Jennifer

AU - Turner, Victoria

AU - Weidinger, Elif

AU - Tarnok, Zsanett

N1 - Funding Information: The EMTICS project has received funding from the European Union’s Seventh Framework Programme for research, technological development, and demonstration under Grant agreement No. 278367. The authors and EMTICS collaborators are grateful to all patients, their siblings, and parents who made this research possible. Publisher Copyright: © 2020 Mac Keith Press Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/10/1

Y1 - 2020/10/1

N2 - Aim: To investigate the association between circulating anti-dopamine D2 receptor (D2R) autoantibodies and the exacerbation of tics in children with chronic tic disorders (CTDs). Method: One hundred and thirty-seven children with CTDs (108 males, 29 females; mean age [SD] 10y 0mo [2y 7mo], range 4–16y) were recruited over 18 months. Patients were assessed at baseline, at tic exacerbation, and at 2 months after exacerbation. Serum anti-D2R antibodies were evaluated using a cell-based assay and blinded immunofluorescence microscopy scoring was performed by two raters. The association between visit type and presence of anti-D2R antibodies was measured with McNemar’s test and repeated-measure logistic regression models, adjusting for potential demographic and clinical confounders. Results: At exacerbation, 11 (8%) participants became anti-D2R-positive (‘early peri-exacerbation seroconverters’), and nine (6.6%) became anti-D2R-positive at post-exacerbation (‘late peri-exacerbation seroconverters’). The anti-D2R antibodies were significantly associated with exacerbations when compared to baseline (McNemar’s odds ratio=11, p=0.003) and conditional logistic regression confirmed this association (Z=3.49, p<0.001) after adjustment for demographic and clinical data and use of psychotropic drugs. Interpretation: There is a potential association between immune mechanisms and the severity course of tics in adolescents with CTDs.

AB - Aim: To investigate the association between circulating anti-dopamine D2 receptor (D2R) autoantibodies and the exacerbation of tics in children with chronic tic disorders (CTDs). Method: One hundred and thirty-seven children with CTDs (108 males, 29 females; mean age [SD] 10y 0mo [2y 7mo], range 4–16y) were recruited over 18 months. Patients were assessed at baseline, at tic exacerbation, and at 2 months after exacerbation. Serum anti-D2R antibodies were evaluated using a cell-based assay and blinded immunofluorescence microscopy scoring was performed by two raters. The association between visit type and presence of anti-D2R antibodies was measured with McNemar’s test and repeated-measure logistic regression models, adjusting for potential demographic and clinical confounders. Results: At exacerbation, 11 (8%) participants became anti-D2R-positive (‘early peri-exacerbation seroconverters’), and nine (6.6%) became anti-D2R-positive at post-exacerbation (‘late peri-exacerbation seroconverters’). The anti-D2R antibodies were significantly associated with exacerbations when compared to baseline (McNemar’s odds ratio=11, p=0.003) and conditional logistic regression confirmed this association (Z=3.49, p<0.001) after adjustment for demographic and clinical data and use of psychotropic drugs. Interpretation: There is a potential association between immune mechanisms and the severity course of tics in adolescents with CTDs.

UR - http://www.scopus.com/inward/record.url?scp=85087733504&partnerID=8YFLogxK

U2 - 10.1111/dmcn.14613

DO - 10.1111/dmcn.14613

M3 - Journal articles

C2 - 32644201

AN - SCOPUS:85087733504

SN - 0012-1622

VL - 62

SP - 1205

EP - 1212

JO - Developmental Medicine and Child Neurology

JF - Developmental Medicine and Child Neurology

IS - 10

ER -

Anti-dopamine D2 receptor antibodies in chronic tic disorders

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