The HLA 8.1 ancestral haplotype in schizophrenia: dual implication in neuro‐synaptic pruning and autoimmunity?

Tamouza, Ryad; Krishnamoorthy, Rajagopal; Giegling, Ina; Leboyer, Marion; Rujescu, Dan

doi:10.1111/acps.13125

Cited by 12 publications

(6 citation statements)

References 10 publications

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“…Although we found associations between the HLA 8.1 AH and severe forms of the BD, i.e. rapid cycling and suicidal behavior 12 , in SZ we observed that the HLA 8.1 AH confers protection or delays age of disease onset 6 , 13 . Given that the HLA cluster is pivotal to both immune processes and brain development, these results suggest that HLA-linked processes may be implicated in mechanisms involved in ontogenic and neurodevelopmental difference between SZ and in BD.…”

Section: Discussioncontrasting

confidence: 71%

“…The MHC/HLA region has been repeatedly shown to be relevant to SZ and BD pathophysiology by a number of experimental approaches, including genome wide association studies (GWAS) 7 – 10 , HLA-imputation methods 11 and HLA-haplotype-based studies 12 , 13 . Unlike the classical HLA alleles which are characterized by an extreme rate of polymorphism, the HLA non classical ones are almost pauci- or monomorphic and therefore provide a means to analyze the role of HLA in human health and disease 14 .…”

Section: Introductionmentioning

confidence: 99%

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HLA-E circulating and genetic determinants in schizophrenia and bipolar disorder

Boukouaci

Lajnef

Richard

et al. 2021

Sci Rep

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Schizophrenia (SZ) and bipolar disorders (BD) are severe mental illnesses that lack reliable biomarkers to guide diagnosis and management. As immune dysregulation is associated with these disorders, we utilized the immunoregulatory functions of the natural killer cell inhibitory HLA-E locus to investigate the relationships between HLA-E genetic and expression diversities with SZ and BD risk and severity. Four hundred and forty-four patients meeting DSM-IV criteria for SZ (N = 161) or BD (N = 283) were compared to 160 heathy controls (HC). Circulating levels of the soluble isoform of HLA-E molecules (sHLA-E) were measured and HLA-E*01:01 and HLA-E*01:03 variants genotyped in the whole sample. sHLA-E circulating levels were significantly higher in both SZ and in BD patients compared to HC (pc < 0.0001 and pc = 0.0007 for SZ and BD, respectively). High sHLA-E levels were also observed in stable SZ patients and in acute BD patients experiencing depressive episodes when comparisons were made between the acute and stable subgroups of each disorder. sHLA-E levels linearly increased along HLA-E genotypes (p = 0.0036). In conclusion, HLA-E variants and level may have utility as diagnostic biomarkers of SZ and BD. The possible roles of HLA diversity in SZ and BD etiology and pathophysiology are discussed.

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Section: Discussioncontrasting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

HLA-E circulating and genetic determinants in schizophrenia and bipolar disorder

Boukouaci

Lajnef

Richard

et al. 2021

Sci Rep

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“…Schizophrenia is a severe mental disorder hallmarked by altered cognition and behavior leading to social and working disability. Recent genetic studies revealed specific polymorphisms in the human leukocyte antigen (HLA) complex involved in psychiatric disorders such as schizophrenia ( Tamouza et al., 2019b ) and in specific forms of autism ( Tamouza et al., 2019a ) as developmental mental disorders accompanied by impaired social and communication skills. A recent study suggested that specific protein-encoding genes might contribute to the development of autoimmunity in psychiatric disorders ( Pouget et al., 2019 ).…”

Section: Immune Dysregulation and Autoimmunity In Major Psychiatric Diseasementioning

confidence: 99%

Autoantibody-associated psychiatric symptoms and syndromes in adults: A narrative review and proposed diagnostic approach

Hansen

Lipp

Vogelgsang

et al. 2020

Brain, Behavior, & Immunity - Health

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Background Autoimmune-mediated encephalitis is a disease that often encompasses psychiatric symptoms as its first clinical manifestation’s predominant and isolated characteristic. Novel guidelines even distinguish autoimmune psychosis from autoimmune encephalitis. The aim of this review is thus to explore whether a wide range of psychiatric symptoms and syndromes are associated or correlate with autoantibodies. Methods We conducted a PubMed search to identify appropriate articles concerning serum and/or cerebrospinal fluid (CSF) autoantibodies associated with psychiatric symptoms and syndromes between 2000 and 2020. Relying on this data, we developed a diagnostic approach to optimize the detection of autoantibodies in psychiatric patients, potentially leading to the approval of an immunotherapy. Results We detected 10 major psychiatric symptoms and syndromes often reported to be associated with serum and/or CSF autoantibodies comprising altered consciousness, disorientation, memory impairment, obsessive-compulsive behavior, psychosis, catatonia, mood dysfunction, anxiety, behavioral abnormalities (autism, hyperkinetic), and sleeping dysfunction. The following psychiatric diagnoses were associated with serum and/or CSF autoantibodies: psychosis and schizophrenia spectrum disorders, mood disorders, minor and major neurocognitive impairment, obsessive-compulsive disorder, autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), anxiety disorders, eating disorders and addiction. By relying on these symptom clusters and diagnoses in terms of onset and their duration, we classified a subacute or subchronic psychiatric syndrome in patients that should be screened for autoantibodies. We propose further diagnostics entailing CSF analysis, electroencephalography and magnetic resonance imaging of the brain. Exploiting these technologies enables standardized and accurate diagnosis of autoantibody-associated psychiatric symptoms and syndromes to deliver early immunotherapy. Conclusions We have developed a clinical diagnostic pathway for classifying subgroups of psychiatric patients whose psychiatric symptoms indicate a suspected autoimmune origin.

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“…Aguiar et al, 0000 , Amare et al, 0000 , Avramopoulos et al, 0000 , Braden and Riecken, 2019 , Brown and Derkits, 2010 , Crespi and Go, 2015 , Creusot et al, 2002 , D'Antonio et al, 0000 , Dendrou et al, 2018 , Psychiatry, 2012 , Eberhard et al, 0000 , Gambino et al, 2018 , Goddard et al, 2007 , Guerini et al, 2018a , Guerini et al, 2018b , Guerini et al, 2019 , Greenig, 0000 , Hegarty et al, 2020 , IMGT, 2020 , Jeppesen and Benros, 2019 , Jézéquel et al, 2017 , Khandaker et al, 2017 , Mackay et al, 2000 , Le Clerc et al, 2015 , Levman et al, 0000 , Limphaibool et al, 2019 , Meltzer, 0000 , Mokhtari and Lachman, 0000 , Pereira et al, 0000 , Perron et al, 2012 , Purcell et al, 2009 , Ripke et al, 2014 , Shah et al, 2019 , Shi et al, 2009 , Stefansson et al, 2009 , Sterner et al, 0000 , Tamouza et al, 2020a , Tamouza et al, 2020b , Verhelst et al, 2011 , Yudofsky, 2009 .…”

Section: Uncited Referencesmentioning

confidence: 99%

Understanding the genetic contribution of the human leukocyte antigen system to common major psychiatric disorders in a world pandemic context

Tamouza¹,

Krishnamoorthy²,

Leboyer³

2021

Brain, Behavior, and Immunity

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Highlights Major psychiatric disorders are associated with genetically-determined immune dysfunctions. Human leukocyte antigen (HLA) molecules are prominent players of immune and neurodevelopmental processes. HLA molecules are encoded by polymorphic genes located in the major histocompatibility complex (MHC). Recent methodological approaches allowed understanding of the HLA genetic complexity and reconcile findings from GWAS in psychiatry. HLA haplotypes studies uncover protective and at risk markers for disease development or proxies of severity in schizophrenia, autism and bipolar disorders. Beyond disease risk, the HLA genetic diversity is associated with autoimmune encephalitis, treatment response, retrovirology and neurodevelopmental immunomodulation. HLA is also involved in anti-infections processes including against the coronavirus family

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The HLA 8.1 ancestral haplotype in schizophrenia: dual implication in neuro‐synaptic pruning and autoimmunity?

Cited by 12 publications

References 10 publications

HLA-E circulating and genetic determinants in schizophrenia and bipolar disorder

HLA-E circulating and genetic determinants in schizophrenia and bipolar disorder

Autoantibody-associated psychiatric symptoms and syndromes in adults: A narrative review and proposed diagnostic approach

Understanding the genetic contribution of the human leukocyte antigen system to common major psychiatric disorders in a world pandemic context

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