Main BETPSY results

HLA and Genetics (WP3) 

Genetics is likely to play an important role in the pathogenesis of Ab-associated autoimmune neurological diseases. Indeed, it is not uncommon that patients or their relatives present with other systemic autoimmune diseases, suggesting a shared predisposition to self-tolerance loss. Human leukocyte antigen (HLA) is the main genetic factor related to autoimmune diseases, accounting for a half of known genetic predisposition. Although more than 200 associations between HLA and disease (immune-mediated or not) have been described, the underlying pathogenic mechanisms remain poorly defined. 

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Anti CASPR2 Article Primary Dq  AutoimmuneAnnotation 2021 04 19 133945

How to improve AE and PNS diagnosis? (WP2)

Paraneoplastic neurologic syndromes (PNSs) are rare but now well-characterized immune-mediated neurologic diseases triggered by cancer and diagnosed by the presence of circulating autoantibodies. Among them, autoantibodies directed against intracellular neural antigens are strongly associated with the presence of an underlying cancer, and its detection is a cornerstone of PNS diagnosis. The commercial diagnostic kits present the advantage to be easily and quickly performed as they are fully automated; they also screen several antibodies at the same time. However, very little is known about the reliability of these immunodot assays, as only a few published studies have analyzed the sensitivity and the specificity for the detection of some autoantibodies.

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Diagnostic Yield

Improvement of anti-GAD65 Abs diagnosis (WP2-WP3)

Neurological syndromes with antibodies against the glutamic acid decarboxylase 65 (GAD65-Ab) are a group of immune-mediated, usually non-paraneoplastic disorders including limbic encephalitis, cerebellar ataxia, and stiff person syndrome. No environmental factor has been strongly associated with these pathogeneses and the primary cause of neurological syndromes with antibodies against GAD 65 is unknown. However, genetic predisposition may exist as it is suggested by the co-occurrence in patients and their relatives of other organ-specific autoimmune diseases. A prompt diagnosis and treatment of patients with autoimmune disease with GAD65-Abs may lead to a better prognosis. 

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Transient NeuroLong TermPrimary DqAnti GAD65


Immune checkpoint inhibitors effects (WP2)

Immune checkpoint inhibitors (ICIs) are novel oncological treatments which show remarkable clinical efficacy in various malignant tumours, including melanoma and lung cancer. ICIs act by enhancing the patient’s immune system to fight cancer but it has been shown that ICIs can also induce paraneoplastic neurological syndromes (PNS). 

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Central Nervous Anti HuAnnotation 2020 12 16 172638

Improvement of Ri-Abs syndromes diagnosis (WP2)

Ri-PNS is characterized by prominent cerebellar and brainstem involvement, followed by multisystem neurologic dysfunction, with a subacute or chronic/progressive course. This could mislead diagnosis toward a neurodegenerative or an inflammatory nonparaneoplastic condition, during which the presence of underlying tumor would not be investigated. Most patients are women with an associated breast tumor, whereas male patients have a wider cancer association. Neurologists should thus be aware of the more complex phenotype associated with Ri antibodies.

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Clinical Spectrum

Epidemiology of PNS and AE (WP1-WP6)

Paraneoplastic neurological syndromes are rare and this rarity makes it difficult to collect large groups of patients in individual centers that would allow carrying out extensive epidemiological studies. Instead, most patients are referred to third-level neuroimmunology institutions, for antibody testing and experimental studies. Our study found an incidence of PNS that approximates 1/100,000 person-years and a prevalence of 4/100,000. Moreover, the incidence of PNS is increasing over time, probably due to increased awareness and improved detection techniques.

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Epidemiology Epidemiology