Epilepsy: An Autoimmune Disease?

[RobinN]

Epilepsy may present as a symptom of many neurological disorders and often an aetiological explanation cannot be identified. There is growing evidence that autoimmune mechanisms might have a role in some patients. This includes numerous reports of the detection of theoretically relevant serum autoantibodies, experimental data showing that antibodies can be epileptogenic, and a response of some epilepsy syndromes to immunomodulation.

The evidence for immunological mechanisms in epilepsy can be examined within the following three main areas: the childhood epilepsy syndromes, epilepsy associated with other immunologically mediated diseases, and the more common unselected groups of patients with epilepsy.

http://jnnp.bmj.com/cgi/content/extract/69/6/711

The concept that the immune system plays a role in the epileptogenic process of some epileptic syndromes was first proposed more than 20 years ago. Since then, numerous studies have reported on the existence of a variety of immunological alterations in epileptic patients, on the observation of favourable responses of refractory epilepsy syndromes to immunomodulatory treatment, and on the association of certain well-known immune-mediated disease states with epilepsy. This review comprehensively recapitulates the currently available evidence supporting or arguing against the possible involvement of the immune system in the pathogenesis of certain types of epilepsy. It is concluded that an abundance of facts is in support of this concept and that further studies should be directed at substantiating the pathogenic significance of (auto)immune responses in certain types of epilepsy. Current progress in the functional and molecular immunological research techniques will indisputably contribute to the elucidation of this link.

http://www.ncbi.nlm.nih.gov/pubmed/...nel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

 

[RobinN]

OBJECTIVE: To investigate whether autoantibodies to ion channels and other neural antigens are present in the sera of patients with epilepsy and seizure-related diseases. METHODS: Sera were obtained from 139 patients, including 26 with preexisting autoimmune disease, 46 in whom an autoimmune basis was suspected, and 67 with drug-resistant epilepsy. The sera were assayed for antibodies to voltage-gated potassium (VGKC) and calcium (VGCC) channels, glutamic acid decarboxylase (GAD), gangliosides, glutamate receptor type 3, cardiolipins, DNA, and nuclear antigens; the results were compared with results from a large cohort of healthy and disease controls. RESULTS: Increased titers of VGKC antibodies (>100 pM) were detected in 16 of 139 (11%) patients with seizures but only 1 control (0.5%). Eight VGKC-positive patients presented with an acute/subacute illness, and 5 of these had the highest VGKC antibodies; 3 patients improved spontaneously, another 5 patients responded well to immunomodulatory therapy. The other VGKC-positive patients had longer disease duration (>6 years) and intermediate levels of antibodies; immunotherapies have not been tested in this group. Very high levels of GAD antibodies (>1,000 U) were found in an additional 3 patients (2.1%) with long-standing drug-resistant epilepsy. CONCLUSIONS: The presence of autoantibodies to voltage-gated potassium channels and glutamic acid decarboxylase suggests that the immune system may contribute to certain forms of epilepsy or seizure-associated disorders. Further studies are needed to determine whether the antibodies are pathogenic.

http://www.ncbi.nlm.nih.gov/pubmed/...nel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

 

[RobinN]

Glutamate is the major excitatory CNS neurotransmitter. Glutamate receptor autoantibodies have now been called to our attention, as they are found in many patients with epilepsy, systemic lupus erythematosus (SLE) and encephalitis, and can unquestionably cause brain damage. AMPA GluR3 autoantibodies have been found thus far in 27% of patients with different epilepsies, while NMDA NR2A or NR2B autoantibodies, some of which cross-react with double-stranded DNA, have been detected in 30% of SLE patients, with or without neuropsychiatric impairments. NR2 autoantibodies were also found in patients with epilepsy (33%), encephalitis and stroke. NR2 and GluR3 autoantibodies do not cross-react in patients with epilepsy. Human and animal studies show that both types of glutamate receptor autoantibodies can certainly damage the brain. GluR3 autoantibodies bind to neurons, possess a unique ability to activate their glutamate-receptor antigen, and cause neuronal death (either by excitotoxicity or by complement fixation independent of receptor activation), multiple brain damage and neurobehavioral/cognitive impairments. In animal models (mice, rats or rabbits) GluR3 autoantibodies may cause seizures, augment their severity or modulate their threshold. NR2/dsDNA autoantibodies, once present in the CNS, can bind and subsequently kill hippocampal and cortical neurons by an excitotoxic complement-independent mechanism. Herein, we discuss epilepsy, autoimmune epilepsy, SLE and neuropsychiatric SLE in general; summarize the up-to-date in vivo and in vitro evidence concerning the presence of glutamate receptor autoantibodies in human diseases; discuss the activity and pathogenicity of different glutamate receptor autoantibodies; and end with our conclusions, recommendations and suggested future directions.

http://www.ncbi.nlm.nih.gov/pubmed/...nel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

 

[RobinN]

PURPOSE OF REVIEW: Celiac disease is an immune-mediated disorder clinically characterized by a multitude of symptoms and complications. The comorbidity between celiac disease and other autoimmune disorders has been clearly established. RECENT FINDINGS: Two main theories have been postulated to explain this comorbidity: (1) linkage disequilibrium between the genes responsible for celiac disease and those responsible for the coexpressed autoimmune diseases or (2) untreated celiac disease leading to the onset of other autoimmune diseases. This article reviews the current literature supporting either theory and places the current knowledge in the field within the context of the most recent data on the pathogenesis of celiac disease. SUMMARY: The current literature did not clearly establish which of the two theories explain the comorbidity between celiac disease and other autoimmune disorders. There is, however, growing evidence that the loss of the intestinal barrier function typical of celiac disease could be responsible of the onset of other autoimmune disease. This concept implies that the autoimmune response can be theoretically stopped and perhaps reversed if the interplay between autoimmune predisposing genes and trigger(s) is prevented or eliminated by a prompt diagnosis and treatment.

http://www.ncbi.nlm.nih.gov/pubmed/...nel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

 

[RobinN]

BACKGROUND: Celiac disease is an autoimmune disorder which may be associated with another autoimmune or systemic disease. OBJECTIVE: To determine the links between autoimmune diseases and celiac disease. PATIENTS AND METHODS: Among 31 patients with a celiac disease, we selected those who had another autoimmune or systemic disease. RESULTS: We report 6 patients with such disease association: 3 with autoimmune thyroiditis including one also with Grave's disease, 2 with systemic lupus erythematosus including one also with insulin-dependent diabetes mellitus, and 1 with temporal arteritis. CONCLUSION: The link between celiac disease and autoimmune thyroiditis or insulin-dependent diabetes mellitus seems to be real but many discrepancies are observed for the other autoimmune diseases. After a literature review, we suggest a summary of effective associations between celiac disease and autoimmune or systemic diseases.

http://www.ncbi.nlm.nih.gov/pubmed/14593308?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=2&log$=relatedreviews&logdbfrom=pubmed

 

[RobinN]

Medical screening is not a tangible existent tool in autoimmune disorders as it is in other illnesses. Numerous attempts are made to identify individuals destined to develop an autoimmune disease, including analysis of the genetic background, which along with the immunological profile, may assist in identifying those individuals. If these efforts turn out to be successful they could lead to proactive measures that might prevent the emergence of such disorders. This review will summarize the attempts made to pursue autoantibodies specific for the central nervous system as potential predictors of autoimmune neurological disorders.

http://www.ncbi.nlm.nih.gov/pubmed/...nel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

 

[RobinN]

Inflammatory reactions occur in the brain in various CNS diseases, including autoimmune, neurodegenerative, and epileptic disorders. Proinflammatory and antiinflammatory cytokines and related molecules have been described in CNS and plasma, in experimental models of seizures and in clinical cases of epilepsy. Inflammation involves both the innate and the adaptive immune systems and shares molecules and pathways also activated by systemic infection. Experimental studies in rodents show that inflammatory reactions in the brain can enhance neuronal excitability, impair cell survival, and increase the permeability of the blood-brain barrier to blood-borne molecules and cells. Moreover, some antiinflammatory treatments reduce seizures in experimental models and, in some instances, in clinical cases of epilepsy. However, inflammatory reactions in brain also can be beneficial, depending on the tissue microenvironment, the inflammatory mediators produced in injured tissue, the functional status of the target cells, and the length of time the tissue is exposed to inflammation. We provide an overview of the current knowledge in this field and attempt to bridge experimental and clinical evidence to discuss critically the possibility that inflammation may be a common factor contributing, or predisposing, to the occurrence of seizures and cell death, in various forms of epilepsy of different etiologies. The elucidation of this aspect may open new perspectives for the pharmacologic treatment of seizures.

http://www.ncbi.nlm.nih.gov/pubmed/...nel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

 

[RobinN]

Having a child with an autoimmune issue made this article interesting to me. I hope it is helpful to others:

A long-term clinical study will investigate the relationship between delayed introduction of gluten during the first year of life and the onset of celiac disease in infants.

“Given the apparently shared underpinning of autoimmune disorders in general, researchers who investigate those conditions are eager to learn whether therapeutic strategies for CD might also ease other autoimmune conditions that currently lack good treatments.”

‘Surprises from Celiac Disease’ examines a connection between the reaction to gluten in those with celiac disease and the onset of other autoimmune diseases. Fasano identifies possible ties through a similar trio of factors that are at the root of the onset of celiac disease and other autoimmune conditions: increased intestine permeability, environmental factors, and a genetic predisposition in patients of celiac disease.

http://vitiligocover.com/celiac-res...campaign=Feed:+VitiligoCover+(Vitiligo+Cover)