Autoimmunity and SARS‐CoV‐2 infection: Unraveling the link in neurological disorders

Latorre, Daniela

doi:10.1002/eji.202149475

Cited by 13 publications

(10 citation statements)

References 122 publications

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“…This suggests that other self-proteins 47 , 48 or immune-mediated mechanisms have a role in post-COVID-19 patients with GBS. In this regard, the high degree of T cell auto-proliferation capacity observed in such cases supports a potential bystander mechanism 49 . Nevertheless, in AIDP cases associated with primary CMV infection, we identified T cells cross-reactive between self and viral antigens, which, in some cases, recognized two distinct PNS-myelin antigens and CMV.…”

Section: Discussionmentioning

confidence: 84%

Autoreactive T cells target peripheral nerves in Guillain–Barré syndrome

Súkeníková,

Mallone,

Schreiner

et al. 2024

Nature

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Guillain–Barré syndrome (GBS) is a rare heterogenous disorder of the peripheral nervous system, which is usually triggered by a preceding infection, and causes a potentially life-threatening progressive muscle weakness1. Although GBS is considered an autoimmune disease, the mechanisms that underlie its distinct clinical subtypes remain largely unknown. Here, by combining in vitro T cell screening, single-cell RNA sequencing and T cell receptor (TCR) sequencing, we identify autoreactive memory CD4+ cells, that show a cytotoxic T helper 1 (TH1)-like phenotype, and rare CD8+ T cells that target myelin antigens of the peripheral nerves in patients with the demyelinating disease variant. We characterized more than 1,000 autoreactive single T cell clones, which revealed a polyclonal TCR repertoire, short CDR3β lengths, preferential HLA-DR restrictions and recognition of immunodominant epitopes. We found that autoreactive TCRβ clonotypes were expanded in the blood of the same patient at distinct disease stages and, notably, that they were shared in the blood and the cerebrospinal fluid across different patients with GBS, but not in control individuals. Finally, we identified myelin-reactive T cells in the nerve biopsy from one patient, which indicates that these cells contribute directly to disease pathophysiology. Collectively, our data provide clear evidence of autoreactive T cell immunity in a subset of patients with GBS, and open new perspectives in the field of inflammatory peripheral neuropathies, with potential impact for biomedical applications.

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Section: Discussionmentioning

confidence: 84%

Autoreactive T cells target peripheral nerves in Guillain–Barré syndrome

Súkeníková,

Mallone,

Schreiner

et al. 2024

Nature

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“…The etiology of neurological complications in PASC is not well understood. Whereas some reports suggest direct SARS‐CoV‐2 invasion of the nervous system, 96 other possible mechanisms include persistent inflammation and rise of autoimmunity, 97 neurotransmitter imbalance, 98 unmasking or exacerbation of prior neurological and neuropsychiatric conditions, 99 and gut–brain axis imbalance 100 . It is likely that there is not just one mechanism but rather different pathophysiological mechanisms that explain PASC in different patient populations.…”

Section: Discussion and Future Directionsmentioning

confidence: 99%

Multidisciplinary collaborative consensus guidance statement on the assessment and treatment of neurologic sequelae in patients with post‐acute sequelae of SARS‐CoV‐2 infection (PASC)

Melamed

Rydberg

Ambrose

et al. 2023

PM&R

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“…This is especially relevant because COVID-19 has been implicated in triggering several neuronal autoimmunities. 8 - 10 …”

Section: Introductionmentioning

confidence: 99%

Severe Stiff-Person Syndrome After COVID

Dalakas

2024

Neurol Neuroimmunol Neuroinflamm

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Objectives To describe a patient with mild GAD-positive stiff-leg syndrome (SLS) who developed severely disabling stiff-person syndrome (SPS) 1 week after mild COVID-19 and discuss the impact of viral implications. Methods Video-documented serial clinical observations at baseline, after acute COVID-19, and after IVIG treatments. Results A 39-year-old man with left-SLS was stable during a 2-year follow-up with low-dose antispasmodics, working fully and functioning normally, even able to run. One week after mild COVID-19, he started to experience generalized SPS symptomatology that steadily worsened the following 2–3 weeks, becoming unable to walk, requiring a walker, with significant thoracolumbar and bilateral leg stiffness and spasms. GAD ab were very high. After 3 monthly IVIg infusions he showed improvements, but his gait remains significantly stiff. All clinical changes, from baseline to post-Covid, and then post- IVIg have been video-documented. Discussion This is the first, clearly documented, severe GAD-positive SPS after COVID-19. Although viral or postviral causation can be incidental, the temporal connection with acute COVID-19, the severe disease worsening after symptom-onset, and the subsequent steady improvement after IVIg, suggest viral-triggered autoimmunity. Because COVID-19 reportedly can trigger or worsen GAD-associated diabetes type 1 through proinflammatory mediators, and SPS has been reportedly triggered by West Nile Virus, possibly through molecular mimicry, this case of acutely converting GAD-SLS to GAD-SPS suggest the need to explore viral etiologies in patients with GAD-SPS experiencing acute, long-lasting episodic exacerbations of stiffness and spasms.

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Autoimmunity and SARS‐CoV‐2 infection: Unraveling the link in neurological disorders

Cited by 13 publications

References 122 publications

Autoreactive T cells target peripheral nerves in Guillain–Barré syndrome

Autoreactive T cells target peripheral nerves in Guillain–Barré syndrome

Multidisciplinary collaborative consensus guidance statement on the assessment and treatment of neurologic sequelae in patients with post‐acute sequelae of SARS‐CoV‐2 infection (PASC)

Severe Stiff-Person Syndrome After COVID

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