Intrathecal synthesis of autoantibodies against tissue transglutaminase

Schrödl, Dominik; Kahlenberg, Franka; Peter-Zimmer, Klaus; Hermann, W.; Kühn, Hans-Jürgen; Mothes, Thomas

doi:10.1016/j.jaut.2004.02.001

Cited by 18 publications

(14 citation statements)

References 43 publications

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“…In positions 1 and 3 in front of the PEQ motif, a P and a Q residue, respectively, occurred significantly more frequently than in peptide group 2. Peptides FSQPEQPFP, SQQPEQPFP, PQQPEQPFP, PLQPEQPFP, PIQPEQPFP, and TQQPEQPFP were recognized by the highest number of sera (36,35,35,35,34, and 32 of 41 sera, respectively). These peptides contained the common heptapeptide motif QPEQPFP.…”

Section: Resultsmentioning

confidence: 97%

“…Increased AGA titers can be found in a variety of other conditions not related to CD, e.g., inflammatory bowel disease (30 ), IgA nephropathy (31 ), HIV infections (32 ), neurologic disorders (33,34 ), and rheumatoid arthritis (35 ) as well as in some apparently healthy individuals. With the discovery of tTG as an autoantigen of CD and its availability as a recombinant human protein for ELISA, the role of AGAs in diagnosis of CD has been decreased.…”

Section: Discussionmentioning

confidence: 99%

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Serologic Assay Based on Gliadin-Related Nonapeptides as a Highly Sensitive and Specific Diagnostic Aid in Celiac Disease

Schwertz¹,

Kahlenberg²,

et al. 2004

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Background: Celiac disease (CD) is induced by wheat gliadins and related cereal proteins. Anti-gliadin antibodies (AGAs) are present in the serum of CD patients, but these antibodies have lower diagnostic specificity and sensitivity than autoantibodies [anti-endomysium antibodies (AEmAs) and anti-tissue transglutaminase antibodies (AtTGAs)]. Recently, AGAs from CD patients were found to recognize deamidated gliadin peptides, probably formed by the action of tissue transglutaminase. Methods: We synthesized several gliadin peptides and their glutamine-glutamic acid-substituted counterparts on cellulose membranes and tested their recognition by IgA in sera of 52 AEmA-positive CD patients and 76 AEmA-negative controls in a luminescence assay. For comparison, we assayed IgA concentrations of AGAs, AtTGAs, and AEmAs. For measurement of AtTGAs, we used the human recombinant antigen. Results: We identified several nonapeptides that were detected with high specificity by IgA in CD patients. Diagnostic accuracy of the peptide antibody assay was highest when peptide PLQPEQPFP was used in combination with peptide PEQLPQFEE within one assay. AGAs were above the cutoff in 14 of the controls, but only 5 of the controls were positive for peptide antibod-

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Section: Resultsmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Serologic Assay Based on Gliadin-Related Nonapeptides as a Highly Sensitive and Specific Diagnostic Aid in Celiac Disease

Schwertz¹,

Kahlenberg²,

et al. 2004

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“…16 The breaching of the blood brain barrier may also facilitate the passage of primed CD4 þ T cells that mounts an immunologic response to tTG6 once this enzyme has been exposed to the CD4 þ T cells as a result of neuroinflammatory events described above. Intrathecal origin of anti-tTG IgA and IgG class has been previously reported, 17 thus suggesting a production of these antibodies within the central nervous system (CNS). CD4 þ T memory cells from the gut and skin have also been previously identified in cerebro-spinal fluid (CSF).…”

Section: Discussionmentioning

confidence: 97%

Increased Prevalence of Transglutaminase 6 Antibodies in Sera From Schizophrenia Patients

Cascella

Santora

Gregory

et al. 2012

Schizophrenia Bulletin

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Gluten can cause extraintestinal manifestations with or without gastrointestinal symptoms and elevated antitissue transglutaminase 2 (tTG2) autoantibodies. Organ-specific gluten reaction involves immune response toward other transglutaminase (TG) isoforms including tTG3 (expressed in the skin, leading to dermatitis herpetiformis) and tTG6 (expressed in the brain, causing gluten ataxia). This analysis focuses on tTG6 antibodies, which have never been studied before in schizophrenia (SZ) and its relationships to tTG2 and to antigliadin antibodies. We previously showed an increased prevalence of tTG2 antibodies in gluten sensitive SZ patients compared with healthy controls (HC) that was not paralleled by an increased prevalence of antiendomysial antibody. To elucidate this discrepancy, we examined those tTG2 positive SZ patients for the presence of tTG6 antibody. We also searched for tTG6 antibodies in our sample of antigliadin (AGA) positive and AGA and tTG2 negative SZ patients. Seventy-four tTG2 positive SZ patients were compared with 148 age and gendermatched HC. Of the 74 tTG2 positive SZ patients, 16 were positive for tTG6 IgA for a prevalence of 22%. Only 4 HC were positive for tTG6 IgA for a prevalence of 2.7%. Among the AGA positive SZ patients, the prevalence of tTG6 IgA was 21.3% while 13.1% of the AGA and tTG2 negative SZ patients were positive for tTG6 IgA. The HC had a prevalence of 6%. Our results indicate a higher prevalence of tTG6 antibodies in SZ that may represent a biomarker useful to identify SZ patients who would benefit from a gluten-free diet.

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“…The Antibody Index (AI) to measure the intrathecal production of antigen-specific antibodies was calculated as follows: [(specific CSF IgG/specific serum IgG)/(total CSF IgG/total serum IgG)] (Mundt L, 2011; Reiber and Peter, 2001; Schrodl et al, 2004). The quantification of an AI when applied properly is a highly sensitive measure of the CSF antibody response and is intended for aiding the accurate and precise documentation of infectious disease diagnoses.…”

Section: Methodsmentioning

confidence: 99%

IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia

Severance¹,

Gressitt²,

Alaedini³

et al. 2015

Brain, Behavior, and Immunity

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Schizophrenia is a complex brain disorder that may be accompanied by idiopathic inflammation. Classic central nervous system (CNS) inflammatory disorders such as viral encephalitis or multiple sclerosis can be characterized by incongruent serum and cerebrospinal fluid (CSF) IgG due in part to localized intrathecal synthesis of antibodies. The dietary antigens, wheat gluten and bovine milk casein, can induce a humoral immune response in susceptible individuals with schizophrenia, but the correlation between the food-derived serological and intrathecal IgG response is not known. Here, we measured IgG to wheat gluten and bovine milk casein in matched serum and CSF samples from 105 individuals with first-episode schizophrenia (n=75 antipsychotic-naïve), and 61 controls. We found striking correlations in the levels of IgG response to dietary proteins between serum and CSF of schizophrenia patients, but not controls (schizophrenia, R2=0.34–0.55, p≤0.0001; controls R2=0.05–0.06, p>0.33). A gauge of blood-CSF barrier permeability and CSF flow rate, the CSF-to-serum albumin ratio, was significantly elevated in cases compared to controls (p≤0.001–0.003). Indicators of intrathecal IgG production, the CSF IgG index and the specific Antibody Index, were not significantly altered in schizophrenia compared to controls. Thus, the selective diffusion of bovine milk casein and wheat gluten antibodies between serum and CSF in schizophrenia may be the function of a low-level anatomical barrier dysfunction or altered CSF flow rate, which may be transient in nature.

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Intrathecal synthesis of autoantibodies against tissue transglutaminase

Cited by 18 publications

References 43 publications

Serologic Assay Based on Gliadin-Related Nonapeptides as a Highly Sensitive and Specific Diagnostic Aid in Celiac Disease

Serologic Assay Based on Gliadin-Related Nonapeptides as a Highly Sensitive and Specific Diagnostic Aid in Celiac Disease

Increased Prevalence of Transglutaminase 6 Antibodies in Sera From Schizophrenia Patients

IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia

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