scholarly journals Th17 cell-mediated immune response in a subpopulation of dogs with idiopathic epilepsy

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262285
Author(s):  
Anna Knebel ◽  
Annika Kämpe ◽  
Regina Carlson ◽  
Karl Rohn ◽  
Andrea Tipold

Background Canine idiopathic epilepsy (IE) is a common neurological disease with severe impact on the owner´s and the dog’s quality of life. A subpopulation of dogs with IE does not respond to antiseizure drugs (non-responder). Th17 cells (T helper cells) and their proinflammatory Interleukin-17 (IL-17) are part of the immune system and previous studies showed their involvement in the pathogenesis of several autoimmune diseases. Non-responder might have an abnormal immune response against structures of the central nervous system. To discover a new aetiology of canine IE and thereby optimising the therapy of intractable IE, this prospective study aimed to investigate Th17 cells and IL-17 in dogs with IE. The underlying hypothesis was that in some dogs with IE a Th17 cell-mediated immune response could be detectable. Methods 57 dogs with IE and 10 healthy dogs (control group, C) were enrolled in the study. EDTA blood was taken to measure Th17 cells by flow cytometry. IL-17 was measured in 35 cerebrospinal fluid (CSF) and 33 serum samples using an enzyme-linked immunosorbent assay (ELISA). It was investigated whether there was a significant increase of stimulated Th17 cells in blood samples or of IL-17 in serum and CSF samples of dogs with IE in comparison to C. Correlations between the amount of Th17 cells/μL or IL-17 and different clinical parameters e.g. seizure frequency, seizure type, seizure severity or treatment response were evaluated. Additionally, Th17 cells/μL were randomly controlled of 17 dogs with IE and were examined for changes over time and in relation to treatment response. Results Ten dogs with IE had strongly elevated stimulated Th17 cells/μL within the blood (>100 Th17 cells/μL). A slight positive correlation between stimulated Th17 cells/μL and seizure severity (p = 0.046; rSpear = 0.27) was proven in these dogs. In addition, 4/10 dogs with elevated Th17 levels experienced cluster seizures and status epilepticus in comparison to 9% of the dogs with non-elevated Th17 levels (<100 Th17 cells/μL). Dogs with IE had significantly higher IL-17 values in CSF and serum samples compared to C (p<0.001; p<0.002; respectively). Conclusion In single dogs with IE, strongly increased amounts of Th17 cells were detectable and dogs with elevated Th17 cells seemed to have a greater risk for experiencing a combination of cluster seizures and status epilepticus. Therefore, an underlying Th17-cell mediated immune response was suspected and hence anti-inflammatory drugs could be indicated in these single cases with intractable epilepsy.

2021 ◽  
Vol 8 ◽  
Author(s):  
Enrice Huenerfauth ◽  
Jasmin Nessler ◽  
Johannes Erath ◽  
Andrea Tipold

Sudden unexpected death in human epileptic patients (SUDEP) is defined as death related to recurrent unprovoked seizures, death occurring unexpectedly, and suddenly in a patient with reasonable state of health, without an obvious medical cause of death, trauma, asphyxia, or intractable status epilepticus, and in post mortem examination no obvious reason for death can be found. “Probable SUDEP” (pSUDEP) is defined as SUDEP not confirmed pathologically. The adapted abbreviation for dogs is used in the following: “pSUDED” (probable sudden unexpected death in dogs with epilepsy). The aim of the present monocentric retrospective study using an online questionnaire was to evaluate the occurrence of pSUDED. Data of canine patients presented with seizures between 01/1998 and 05/2018 were retrospectively analyzed and classified according to their etiology (n = 1,503). Owners were contacted by telephone to participate in answering a validated questionnaire. A total of 509 owners were reached, and 373 owners completed the questionnaire. In addition to signalement (e.g., breed), special attention was paid to the frequency and presentation of seizures and seizures in the context of death. Fifty-one percent (191/373) of the dogs were dead at the endpoint of the study. A large proportion of the dogs was euthanized (149/191) because of seizure severity or health problems unrelated to seizures. Idiopathic epilepsy (IE) was diagnosed in 19/34 dogs which died unexpectedly. Of these seven animals had to be excluded for further investigation of pSUDED because of status epilepticus or aspiration pneumonia as a result of the seizures. In 12 dogs with IE the last seizure event occurred between 6 h and ~3 months before death. pSUDED was suspected in these dogs and an occurrence rate of 4.5–10% was calculated. pSUDED appears in a similar occurrence rate as human SUDEP and should be considered as a possible complication in epileptic dogs. The results of this study suggest that dogs with IE but especially those with brachycephalic syndrome and cluster seizures have an increased risk to die of pSUDED. Owners of dogs with seizures should be educated about the risk of sudden death in dogs with epilepsy.


2008 ◽  
Vol 56 (4) ◽  
pp. 471-483 ◽  
Author(s):  
Ákos Pákozdy ◽  
Michael Leschnik ◽  
Alexander Tichy ◽  
Johann Thalhammer

In the present study, 240 cases of dogs with seizures were analysed retrospectively. The aim was to examine the underlying aetiology and to compare primary or idiopathic epilepsy (IE) with symptomatic epilepsy (SE) concerning signalment, history, ictal pattern, clinical and neurological findings. The diagnosis of symptomatic epilepsy was based on confirmed pathological changes in haematology, serum biochemistry, cerebrospinal fluid (CSF) analysis and morphological changes of the brain by CT/MRI or histopathological examination. Seizure aetiologies were classified as idiopathic epilepsy (IE, n = 115) and symptomatic epilepsy (SE, n = 125). Symptomatic epilepsy was mainly caused by intracranial neoplasia (39) and encephalitis (23). The following variables showed significant difference between the IE and SE group: age, body weight, presence of partial seizures, cluster seizures, status epilepticus, ictal vocalisation and neurological deficits. In 48% of the cases, seizures were found to be due to IE, while 16% were due to intracranial neoplasia and 10% to encephalitis. Status epilepticus, cluster seizures, partial seizures, vocalisation during seizure and impaired neurological status were more readily seen with symptomatic epilepsy. If the first seizure occurred between one and five years of age or the seizures occurred during resting condition, the diagnosis was more likely IE than SE.


Author(s):  
Christian Maeso ◽  
Daniel Sánchez-Masian ◽  
Sergio Ródenas ◽  
Cristina Font ◽  
Carles Morales ◽  
...  

Abstract OBJECTIVE To determine the prevalence of presumed postictal changes (PC) on brain MRI in epileptic dogs, describe their distribution, and recognize possible correlations with different epilepsy features. ANIMALS 540 client-owned dogs with epilepsy and a complete medical record that underwent brain MRI at 4 veterinary referral hospitals between 2016 and 2019. PROCEDURES Data were collected regarding signalment, seizure type, seizure severity, time between last seizure and MRI, and etiological classification of epilepsy. Postictal changes were considered when solitary or multiple intraparenchymal hyperintense lesions were observed on T2-weighted and fluid-attenuated inversion recovery images and were hypointense or isointense on T1-weighted sequences, which were not confined to a vascular territory and showed no to mild mass effect and no to mild contrast enhancement. RESULTS Sixty-seven dogs (12.4%) showed MRI features consistent with PC. The most common brain sites affected were the piriform lobe, hippocampus, temporal neocortex, and cingulate gyrus. Dogs having suffered cluster seizures or status epilepticus were associated with a higher probability of occurrence of PC, compared to dogs with self-limiting seizures (OR 2.39; 95% confidence interval, 1.33 to 4.30). Suspected PC were detected both in dogs with idiopathic epilepsy and in those with structural epilepsy. Dogs with unknown-origin epilepsy were more likely to have presumed PC than were dogs with structural (OR 0.15; 95% confidence interval, 0.06 to 0.33) or idiopathic epilepsy (OR 0.42; 95% confidence interval, 0.20 to 0.87). Time between last seizure and MRI was significantly shorter in dogs with PC. CLINICAL RELEVANCE MRI lesions consistent with PC were common in epileptic dogs, and the brain distribution of these lesions varied. Occurrence of cluster seizures or status epilepticus, diagnosis of unknown origin epilepsy, and lower time from last seizure to MRI are predictors of suspected PC.


PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e72732 ◽  
Author(s):  
Rafael Cáliz ◽  
Luz María Canet ◽  
Carmen Belén Lupiañez ◽  
Helena Canhão ◽  
Alejandro Escudero ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Junxia Huang ◽  
Xinzhi Xu ◽  
Ji Yang

T helper 17 (Th17) cells are characterized by the secretion of the IL-17 cytokine and are essential for the immune response against bacterial and fungal infections. Despite the beneficial roles of Th17 cells, unrestrained IL-17 production can contribute to immunopathology and inflammatory autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. Although these diverse outcomes are directed by the activation of Th17 cells, the regulation of Th17 cells is incompletely understood. The discovery that microRNAs (miRNAs) are involved in the regulation of Th17 cell differentiation and function has greatly improved our understanding of Th17 cells in immune response and disease. Here, we provide an overview of the biogenesis and function of miRNA and summarize the role of miRNAs in Th17 cell differentiation and function. Finally, we focus on recent advances in miRNA-mediated dysregulation of Th17 cell fate in autoimmune diseases.


2021 ◽  
pp. 1098612X2110367
Author(s):  
Marianne Tenger ◽  
Sofie Van Meervenne ◽  
Katarina Varjonen ◽  
Anna Tidholm ◽  
Cecilia Rohdin

Objectives The primary objective of this study was to investigate the prevalence of epileptic seizures and of presumed idiopathic epilepsy (PIE, describing epilepsy of unknown origin) in a cohort of British Shorthair (BSH) cats in Sweden. The secondary objective was to describe epileptic seizure characteristics and outcome for cats with PIE. Methods Owners of BSH cats born between 2006 and 2016 and registered with SVERAK (the Swedish Cat Clubs’ National Association) were invited to reply to a questionnaire about their cat’s general health. Owners who indicated that their cat had experienced epileptic seizures were invited to participate in an in-depth telephone interview about the epileptic seizures. The clinical characteristics of epileptic seizures in BSH cats were determined from the results of the interview. Results In this population comprising 1645 BSH cats (representing 28% of registered BSHs), the prevalence of epileptic seizures was 0.9% and for PIE it was 0.7%. BSH cats with PIE presented with infrequent but consistent epileptic seizures. Twenty-seven percent of BSH cats with epileptic seizures had cluster seizures but none presented with status epilepticus. None of the BSH cats was treated with antiepileptic drugs, and none of the owners reported epileptic seizure remission in their cat. Conclusions and relevance The prevalence of PIE in this population of BSH cats was 0.7%. The prevalence of epileptic seizures was 0.9%. In general, PIE in the BSH cat displayed a relatively benign phenotype where progression of epileptic seizures was uncommon.


2011 ◽  
Vol 208 (11) ◽  
pp. 2321-2333 ◽  
Author(s):  
Qingguo Ruan ◽  
Vasumathi Kameswaran ◽  
Yan Zhang ◽  
Shijun Zheng ◽  
Jing Sun ◽  
...  

The Th17 cells use the retinoid-related orphan receptor-γ (Rorg or Rorc) to specify their differentiation and lineage-specific function. However, how Rorg is switched on during Th17 differentiation is unknown. We report here that c-Rel and RelA/p65 transcription factors drive Th17 differentiation by binding to and activating two distinct Rorg promoters that control RORγT and RORγ expression, respectively. Similar to RORγT, RORγ is selectively expressed in Th17 cells and is effective in specifying the Th17 phenotype. T cells deficient in c-Rel or RelA are significantly compromised in Th17 differentiation, and c-Rel–deficient mice are defective in Th17 responses. Thus, Th17 immunity is controlled by a Rel–RORγ–RORγT axis, and strategies targeting Rel/NF-κB can be effective for controlling Th17 cell–mediated diseases.


2016 ◽  
Vol 94 (suppl_1) ◽  
pp. 71-71
Author(s):  
K. C. Garrett ◽  
D. A. Neuendorff ◽  
A. W. Lewis ◽  
S. T. Willard ◽  
T. H. Welsh ◽  
...  

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