Francesco Addabbo1, Valentina Baglioni2, Anette Schrag3, Markus J Schwarz4, Andrea Dietrich5, Pieter J Hoekstra5, Davide Martino6, Maura Buttiglione1. 1. Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Bari, Italy. 2. Department of Human Neurosciences, Sapienza University of Rome, Institute of Child and Adolescent Neurology and Psychiatry, Rome, Italy. 3. Department of Clinical Neurosciences, UCL Institute of Neurology, Royal Free Campus, London, UK. 4. Institute of Laboratory Medicine, University Hospital, LMU Munich, Munich, Germany. 5. Department of Child and Adolescent Psychiatry, University Medical Center Groningen, Groningen, the Netherlands. 6. Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Health Sciences Centre, Calgary, AB, Canada.
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.
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.
Authors: Deepti Pilli; Alicia Zou; Ruebena Dawes; Joseph A Lopez; Fiona Tea; Ganesha Liyanage; Fiona Xz Lee; Vera Merheb; Samuel D Houston; Aleha Pillay; Hannah F Jones; Sudarshini Ramanathan; Shekeeb Mohammad; Anthony D Kelleher; Stephen I Alexander; Russell C Dale; Fabienne Brilot Journal: Clin Transl Immunology Date: 2020-12-17