Altered frequencies of Th17 and Treg cells in children and adolescents with obsessive-compulsive disorder

Rodríguez, Natàlia; Morer, Àstrid; González-Navarro, Europa Azucena; Serra-Pagès, Carles; Boloc, Daniel; Torres, Teresa; Martínez-Pinteño, Albert; Mas, Sergi; Lafuente, Amàlia; Gassó, Patricia; Lázaro, Luisa

doi:10.1016/j.bbi.2019.07.022

Cited by 22 publications

(23 citation statements)

References 71 publications

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“…On the other hand, D2R‐specific T‐cell‐positive patients with neurodevelopmental disorders had a chronic disease course and Tourette's syndrome concomitant with OCD was the prominent feature. This result supports the existing paradigm of dopamine dysregulation in Tourette's syndrome 17,44,45 and is consistent with the recent report of altered frequencies in functional subsets of circulating CD4 + T cells in paediatric patients with OCD 46 . While PANS was a common feature in our cohort and recent findings have suggested neuroinflammatory involvement, 25 D2R‐specific T cells were not observed in these patients.…”

Section: Discussionsupporting

confidence: 93%

“…This result supports the existing paradigm of dopamine dysregulation in Tourette's syndrome 17,44,45 and is consistent with the recent report of altered frequencies in functional subsets of circulating CD4 + T cells in paediatric patients with OCD. 46 While PANS was a common feature in our cohort and recent findings have suggested neuroinflammatory involvement, 25 D2R-specific T cells were not observed in these patients. D2Rspecific T cells were identified in both an acute course and chronic course of movement and psychiatric disorders, suggesting different modes of T-cell activity in different disease courses.…”

Section: Discussionmentioning

confidence: 45%

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Pro‐inflammatory dopamine‐2 receptor‐specific T cells in paediatric movement and psychiatric disorders

et al. 2020

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Objectives A dysregulated inflammatory response against the dopamine‐2 receptor (D2R) has been implicated in movement and psychiatric disorders. D2R antibodies were previously reported in a subset of these patients; however, the role of T cells in these disorders remains unknown. Our objective was to identify and characterise pro‐inflammatory D2R‐specific T cells in movement and psychiatric disorders. Methods Blood from paediatric patients with movement and psychiatric disorders of suspected autoimmune and neurodevelopmental aetiology (n = 24) and controls (n = 16) was cultured in vitro with a human D2R peptide library, and D2R‐specific T cells were identified by flow cytometric quantification of CD4+CD25+CD134+ T cells. Cytokine secretion was analysed using a cytometric bead array and ELISA. HLA genotypes were examined in D2R‐specific T‐cell‐positive patients. D2R antibody seropositivity was determined using a flow cytometry live cell‐based assay. Results Three immunodominant regions of D2R, amino acid (aa)121–131, aa171–181 and aa396–416, specifically activated CD4+ T cells in 8/24 patients. Peptides corresponding to these regions were predicted to bind with high affinity to the HLA of the eight positive patients and had also elicited the secretion of pro‐inflammatory cytokines IL‐2, IFN‐ γ, TNF, IL‐6, IL‐17A and IL‐17F. All eight patients were seronegative for D2R antibodies. Conclusion Autoreactive D2R‐specific T cells and a pro‐inflammatory Th1 and Th17 cytokine profile characterise a subset of paediatric patients with movement and psychiatric disorders, further underpinning the theory of immune dysregulation in these disorders. These findings offer new perspectives into the neuroinflammatory mechanisms of movement and psychiatric disorders and can influence patient diagnosis and treatment.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 45%

Pro‐inflammatory dopamine‐2 receptor‐specific T cells in paediatric movement and psychiatric disorders

et al. 2020

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“…Interestingly, this difference was significant only in males (113). Another controlled clinic-based study on 99 youth with OCD and 46 healthy volunteers showed higher frequencies of T-helper (Th)17 cells and lower percentages of Tregs in OCD (114). These changes became more marked as disease duration and severity increased and were independent of the comorbidity profile or exposure to psychoactive substances, suggesting the possibility of progressive immune dysregulation in OCD.…”

Section: Ocdmentioning

confidence: 98%

What Does Immunology Have to Do With Normal Brain Development and the Pathophysiology Underlying Tourette Syndrome and Related Neuropsychiatric Disorders?

2020

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The goal of this article is to review the past decade's literature and provide a critical commentary on the involvement of immunological mechanisms in normal brain development, as well as its role in the pathophysiology of Tourette syndrome, other Chronic tic disorders (CTD), and related neuropsychiatric disorders including Obsessive-compulsive disorder (OCD) and Attention deficit hyperactivity disorder (ADHD). Methods: We conducted a literature search using the Medline/PubMed and EMBASE electronic databases to locate relevant articles and abstracts published between 2009 and 2020, using a comprehensive list of search terms related to immune mechanisms and the diseases of interest, including both clinical and animal model studies. Results: The cellular and molecular processes that constitute our "immune system" are crucial to normal brain development and the formation and maintenance of neural circuits. It is also increasingly evident that innate and adaptive systemic immune pathways, as well as neuroinflammatory mechanisms, play an important role in the pathobiology of at least a subset of individuals with Tourette syndrome and related neuropsychiatric disorders In the conceptual framework of the holobiont theory, emerging evidence points also to the importance of the "microbiota-gut-brain axis" in the pathobiology of these neurodevelopmental disorders. Conclusions: Neural development is an enormously complex and dynamic process. Immunological pathways are implicated in several early neurodevelopmental processes including the formation and refinement of neural circuits. Hyper-reactivity of systemic immune pathways and neuroinflammation may contribute to the natural fluctuations of the core behavioral features of CTD, OCD, and ADHD. There is still limited knowledge of the efficacy of direct and indirect (i.e., through environmental modifications) immune-modulatory interventions in the treatment of these disorders. Future research also needs to focus on the key molecular pathways through which dysbiosis of different tissue microbiota influence neuroimmune interactions in these disorders, Martino et al. Immunity in TS/CTD, OCD, and ADHD and how microbiota modification could modify their natural history. It is also possible that valid biomarkers will emerge that will guide a more personalized approach to the treatment of these disorders.

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“…Adults with psoriatic arthritis and ankylosing spondylitis have been found to have increased rates of obsessive-compulsive symptoms, anger-hostility, paranoid ideation, somatization, anxiety, depression, and self-harm. (9) (10) (11) (12) (13) (14) While rheumatoid arthritis (RA) patients with depression have poorer RA outcomes (i.e., worse mortality, more comorbidities and higher pain levels). (15) Patients with juvenile SpA and polyarthritis have worse self-reported pain, physical functioning, remission rates and quality of life, putting them at high risk for psychopathology.…”

Section: Introductionmentioning

confidence: 99%

Profiling Behavioral and Psychological Symptoms in Children Undergoing Treatment for Spondyloarthritis and Polyarthritis

et al. 2022

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Objective Few studies examine psychopathology in different juvenile idiopathic arthritis (JIA) subtypes and disease activity states. We aimed to 1) Evaluate emotional and behavioral symptoms in children with spondyloarthritis (SpA) and polyarticular arthritis (PolyA) as compared to a national normative population using the Child Behavior Checklist (CBCL), and 2) Evaluate the relationship between CBCL scores and disease activity. Methods JIA patients aged 6-17 years with SpA or PolyA were recruited from our Pediatric Rheumatology clinic from April 2018 to April 2019 and the CBCL and Juvenile Arthritis Disease Activity Score (cJADAS10) were completed. Primary outcome measures were CBCL total competence, internalizing, externalizing and total problems raw scores. We compared outcomes from each group to national CBCL normative data. To investigate the relationship between CBCL scores and disease activity, we ran a generalized linear regression model for all arthritis patients with cJADAS10 as the main predictor. Results There were 111 patients and 1753 healthy controls. Compared to healthy controls, SpA or PolyA patients had worse total competence and internalizing scores. Higher cJADAS10 scores were associated with worse total competence, worse internalizing, and higher total problems scores. Most of these differences reached statistical significance (p<0.01). Self-harm/ suicidality was almost four-fold higher in patients with PolyA than healthy controls (OR 3.6, 95% CI 1.3-9.6, p=0.011). Conclusion Our study shows that SpA and PolyA patients with more active disease have worse psychological functioning in activities, school and social arenas and more internalized emotional disturbances suggesting the need for regular mental health screening by rheumatologists.

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Altered frequencies of Th17 and Treg cells in children and adolescents with obsessive-compulsive disorder

Cited by 22 publications

References 71 publications

Pro‐inflammatory dopamine‐2 receptor‐specific T cells in paediatric movement and psychiatric disorders

Pro‐inflammatory dopamine‐2 receptor‐specific T cells in paediatric movement and psychiatric disorders

What Does Immunology Have to Do With Normal Brain Development and the Pathophysiology Underlying Tourette Syndrome and Related Neuropsychiatric Disorders?

Profiling Behavioral and Psychological Symptoms in Children Undergoing Treatment for Spondyloarthritis and Polyarthritis

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