Increased Prevalence of Transglutaminase 6 Antibodies in Sera From Schizophrenia Patients

Cascella, Nicola G.; Santora, Debby; Gregory, Patricia; Kelly, Deanna L.; Fasano, Alessio; Eaton, William W.

doi:10.1093/schbul/sbs064

Cited by 34 publications

(24 citation statements)

References 19 publications

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“…Patients seropositive for TG6 IgA antibodies showed a clinical presentation similar to that of patients negative for these antibodies regarding age at disease onset, proportion of bulbar cases, and sex distribution, much like the presentation of patients with schizophrenia. 15 This similarity opposes the reported relatively early onset of disease in patients with gluten ataxia who are seropositive for TG6 IgA antibodies. 24 Production of TG6 autoantibodies was not significantly associated with a familial history of ALS.…”

Section: Clinical Presentation In Patients With or Without Tg6 Autoanmentioning

confidence: 76%

“…The TG6 antibody titer is dependent on gluten ingestion. 14 In addition, TG6 antibodies have been reported in gluten neuropathy, 12 schizophrenia, 15 cerebral palsy, 16 and a rare neurologic syndrome associated with epilepsy and cerebral calcification. 17 Other neurologic syndromes, such as epilepsy, encephalopathy, dementia, myopathy, myelopathy, multiple sclerosis, stiffman syndrome, and myoclonic ataxia, have been rarely reported in association with gluten sensitivity.…”

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confidence: 99%

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Transglutaminase 6 Antibodies in the Serum of Patients With Amyotrophic Lateral Sclerosis

Gadoth¹,

Bleiberg²,

Klein

et al. 2015

JAMA Neurol

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IMPORTANCE Celiac disease is an autoimmune disorder triggered by gluten in genetically predisposed individuals. Gluten sensitivity can cause neurologic manifestations, such as ataxia or neuropathy, with or without gastrointestinal symptoms. Many patients with gluten ataxia produce antibodies toward the newly identified neuronal transglutaminase 6 (TG6). Two case reports described patients initially diagnosed with amyotrophic lateral sclerosis (ALS) and ultimately with celiac disease who improved with a strict gluten-free diet. OBJECTIVE To evaluate the prevalence of celiac disease-related antibodies and HLA antigen alleles, as well as TG6 antibodies, in patients with ALS and healthy individuals serving as controls to determine whether a neurologic presentation of a gluten-related disorder mimicking ALS might occur in some patients. DESIGN, SETTING, AND PARTICIPANTS In a case-control study conducted in an ALS tertiary center, we measured serum levels of total IgA antibodies, IgA antibodies to transglutaminase 2 (TG2) and endomysium, as well as IgA and IgG antibodies to deamidated gliadine peptide and TG6 and performed HLA antigen genotyping in 150 consecutive patients with ALS and 115 healthy volunteers of similar age and sex. Participants did not have any known autoimmune or gastroenterologic disorder and were not receiving any immunomodulatory medications. The study was conducted from July 1, 2010, to December 31, 2012. MAIN OUTCOMES AND MEASURES Antibody levels and frequency of individuals with abnormal antibody values as well as frequency of HLA antigen alleles were compared between patient and control groups. RESULTS All patients and control group participants were seronegative to IgA antibodies to TG2, endomysium, and deamidated gliadine peptide. Twenty-three patients (15.3%) were seropositive to TG6 IgA antibodies as opposed to only 5 controls (4.3%) (P = .004). The patients seropositive for TG6 showed a classic picture of ALS, similar to that of seronegative patients. Fifty patients and 20 controls were tested for celiac disease-specific HLA antigen alleles; 13 of 22 TG6 IgA seropositive individuals (59.1%) were seropositive for celiac disease-related alleles compared with 8 (28.6%) of the 28 seronegative individuals (P = .04). Mean (SD) levels of IgA antibodies to TG2 were 1.78 (0.73) in patients and 1.58 (0.68) in controls (normal, <10). In a subset of study participants, mean levels of deamidated gliadin peptide autoantibodies were 7.46 (6.92) in patients and 6.08 (3.90) in controls (normal, <16). Mean levels of IgA antibodies to TG6 were 29.3 (30.1) in patients and 21.0 (27.4) in controls (P = .02; normal, <26). CONCLUSIONS AND RELEVANCE The data from this study indicate that, in certain cases, an ALS syndrome might be associated with autoimmunity and gluten sensitivity. Although the data are preliminary and need replication, gluten sensitivity is potentially treatable; therefore, this diagnostic challenge should not be overlooked.

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Section: Clinical Presentation In Patients With or Without Tg6 Autoanmentioning

confidence: 76%

mentioning

confidence: 99%

Transglutaminase 6 Antibodies in the Serum of Patients With Amyotrophic Lateral Sclerosis

Gadoth¹,

Bleiberg²,

Klein

et al. 2015

JAMA Neurol

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“…The analysis was focused on tTG6 antibodies and their relationship to anti-tissue transglutaminase 2 (tTG2) and to antigliadin antibodies. Results indicated a higher prevalence of tTG6 antibodies in schizophrenia and confirmed that it may be a useful biomarker to identify patients whose gluten-free diet can potentially contribute to the improvement of symptoms (Cascella et al, 2012). …”

Section: Immunologic Studies (Reported By M Dmitrzak-węglarz Alekmentioning

confidence: 73%

The 3rd Schizophrenia International Research Society Conference, 14–18 April 2012, Florence, Italy: Summaries of oral sessions

Abbs¹,

Achalia²,

Adelufosi³

et al. 2012

Schizophrenia Research

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The 3rd Schizophrenia International Research Society Conference was held in Florence, Italy, April 14-18, 2012.and this year had as its emphasis, “The Globalization of Research”. Student travel awardees served as rapporteurs for each oral session and focused their summaries on the most significant findings that emerged and the discussions that followed. The following report is a composite of these summaries. We hope that it will provide an overview for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research.

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“…An immune-mediated reaction to gluten could trigger a neuroinflammatory process, with associated impairment of the permeability of the blood-brain barrier. We recently reported an increased prevalence of antibodies for transglutaminase 6, specifically expressed in the brain, in schizophrenia patients who were positive for AGA antibodies (25). We described the findings as a marker of neuroinflammation in gluten-sensitive schizophrenia patients.…”

Section: Discussionmentioning

confidence: 99%

Improvement in Psychotic Symptoms After a Gluten-Free Diet in a Boy With Complex Autoimmune Illness

Eaton¹,

Chen

Dohan

et al. 2015

AJP

Self Cite

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CASE PRESENTATION At age 8, “Chris,” a Caucasian boy, experienced intermittent auditory and visual hallucinations, but without bizarre behaviors or much deterioration in functioning. At age 15, he developed a depressed mood, started talking to himself, and became socially withdrawn, and his academic performance declined. He was hospitalized and diagnosed as having major depressive disorder with psychotic features. MRI and EEG showed no abnormalities. Treatment with escitalopram (10 mg/day) and aripiprazole (5 mg/day) had little effect. Several weeks after discharge, he was admitted for a second time with the same diagnosis; a third admission, again with the same diagnosis, occurred several months after that. At age 16, Chris developed visual and auditory hallucinations with homicidal ideations. He cut himself superficially following the command of voice hallucinations, and he was hospitalized again, with the diagnosis changed to schizophrenia, paranoid type. During this inpatient stay, he was treated with venlafaxine (150 mg/day) and risperidone (1.5 mg/day). During the same admission, a blood test showed the presence of antinuclear antibodies (ANAs), but the patient had no symptoms of any autoimmune disease. In the meantime, he was also receiving clindamycin/benzoyl peroxide and adapaline gels and minocycline for acne and fluticasone nasal spray and albuterol for asthma. An allergy to gluten was demonstrated by an assay (Accessa Labs) that showed only IgE antigluten antibodies. Chris’sparents reported that he developed anallergy to peanuts and soy at about the same time. Gluten was removed from his diet at the suggestion of the mother, a licensed dietitian. After the dietary change, the intensity of Chris’s auditory hallucinations declined dramatically and the violent element diminished, and he was discharged after 9 weeks. During the next 2 years, Chris remained on a gluten-free diet, which he and his family associated with the disappearance of his psychotic symptoms. Sensitivity to gluten was demonstrated by an assay (Metametrix Clinical Laboratory) of a stool sample that yielded a value of 10.6 mg/dL of IgA antigliadin antibodies, in the top quintile of the reference range. The dosage of risperidone was tapered to 0.5 mg/day, and no auditory or visual hallucinations occurred, although when the dosage was lowered to 0.25 mg/day, Chris reported feeling anxious, and the dosage was returned to 0.5 mg/day for a time. Eventually the risperidone was discontinued completely. Chris was able to return to school, where his academic performance was normal and he joined several athletic teams. At age 16, after his hospital stay, Chris lost his hearing suddenly and was fitted with a hearing aid. His ANA level was high, and the diagnosis of autoimmune inner ear disease was made. He was treated with prednisone and then methotrexate over a 2-month period. Despite his hearing loss, he has maintained a high level of functioning, including learning to read lips, and he has continued to play competitive sports. Both of Chris’s p...

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Increased Prevalence of Transglutaminase 6 Antibodies in Sera From Schizophrenia Patients

Cited by 34 publications

References 19 publications

Transglutaminase 6 Antibodies in the Serum of Patients With Amyotrophic Lateral Sclerosis

Transglutaminase 6 Antibodies in the Serum of Patients With Amyotrophic Lateral Sclerosis

The 3rd Schizophrenia International Research Society Conference, 14–18 April 2012, Florence, Italy: Summaries of oral sessions

Improvement in Psychotic Symptoms After a Gluten-Free Diet in a Boy With Complex Autoimmune Illness

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