[Llonghair]

Just in case this hasn't been posted.

http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15082580
: Gut. 2004 May;53(5):641-8. Links
In vivo targeting of intestinal and extraintestinal transglutaminase 2 by coeliac autoantibodies.
• Korponay-Szabo IR,
• Halttunen T,
• Szalai Z,
• Laurila K,
• Kiraly R,
• Kovacs JB,
• Fesus L,
• Maki M.
Paediatric Research Centre, Tampere University Hospital, Tampere, Finland.
BACKGROUND: IgA class serum autoantibodies against type 2 (tissue) transglutaminase (TG2) bind to both intestinal and extraintestinal normal tissue sections in vitro, eliciting endomysial, reticulin, and jejunal antibody reactions. It is not known whether similar binding also occurs in coeliac patients in vivo, and may thereby contribute to disease manifestations. AIMS: To investigate intestinal and extraintestinal coeliac tissues for the presence of in vivo bound TG2 specific IgA and its relation to small intestinal mucosal atrophy. PATIENTS: We investigated jejunal samples with normal villous morphology from 10 patients with developing coeliac disease who subsequently progressed to a flat lesion, from 11 patients with dermatitis herpetiformis, and from 12 non-coeliac controls. Six extrajejunal biopsy samples (liver, lymph node, muscle, appendix), obtained based on independent clinical indications from patients with active coeliac disease, were also studied. METHODS: Double colour immunofluorescent studies for in situ IgA, TG2, and laminin were performed. IgA was eluted from tissue sections and tested for TG2 specificity by enzyme linked immunosorbent assay and indirect immunofluorescence. RESULTS: IgA (in one IgA deficient case IgG) deposition on extracellularly located TG2 was detected in jejunal and extrajejunal specimens of all coeliac patients, and also in seven of 11 dermatitis herpetiformis patients, of whom two had no circulating endomysial antibodies. IgA eluted from extraintestinal coeliac tissues was targeted against TG2. CONCLUSIONS: Coeliac IgA targets jejunal TG2 early in disease development even when endomysial antibodies are not present in the circulation. Extraintestinal target sites of coeliac IgA further indicate that humoral immunity may have a pathogenetic role.PMID: 15082580 [PubMed - indexed for MEDLINE]

[annelb]

Ok, someone help me understand what is being said.

I think it says they found a tissue transglutaminase reaction in the gut tissue before the blood tests were positive. Would this have anything to do with the tissue transglutaminase Dr. Fine tests? Does he find the same thing by examining the stool?

Guess we will have to read the complete article to find out where the extraintestinal sites mentioned are located.

Anne

[jccgf]

Here are others. I think they are all suggesting that these TG2-related immunoglobulin deposits can be found in patients who are sero-negative and despite normal small-bowel mucosal villous architecture.

Right????






Endomysial antibodies with normal histology indicates early developing coeliac disease. Transglutaminase 2-targeted intestinal autoantibody deposits proved the best predictor of subsequent coeliac disease.
Immunoglobulin A autoantibodies against transglutaminase 2 in the small intestinal mucosa predict forthcoming coeliac disease. PMID: 16886921 Aug 2006

BACKGROUND: Reliable markers of early developing coeliac diseases are needed. Coeliac autoantibodies in the serum or Marsh I inflammation may be indicators of subsequent coeliac disease. AIM: To investigate whether determination of intestinal transglutaminase 2-targeted autoantibody deposits would detect early developing coeliac disease better than previous methods. METHODS: The study investigated patients previously excluded for coeliac disease: 25 had positive serum coeliac autoantibodies (endomysial), 25 antibody-negative had Marsh I, and 25 antibody-negative had Marsh 0 finding. Seven (median) years after baseline investigation, new coeliac cases were recorded, and small bowel biopsy was offered to the rest of the patients. Serum and intestinal coeliac autoantibodies and intraepithelial lymphocytes were assessed as indicators of developing coeliac disease. RESULTS: Seventeen patients had developed coeliac disease: 13 in the autoantibody-positive group, three in the Marsh I group and one in the Marsh 0 group. At baseline, intestinal coeliac autoantibody deposits had a sensitivity and specificity of 93% and 93% in detecting subsequent coeliac disease, CD3+ 59% and 57%, gammadelta+ 76% and 60%, and villous tip intraepithelial lymphocytes 88% and 71%, respectively. CONCLUSIONS: Endomysial antibodies with normal histology indicates early developing coeliac disease. Transglutaminase 2-targeted intestinal autoantibody deposits proved the best predictor of subsequent coeliac disease.
PMID: 16886921

Endomysial antibody-negative coeliac disease: clinical characteristics and intestinal autoantibody deposits. PMID: 16571636 Mar 2006

BACKGROUND: Some untreated coeliac disease patients are negative for serum endomysial autoantibodies (EmA) targeted against transglutaminase 2 (TG2). AIMS: To evaluate the clinical and histological features of EmA-negative coeliac disease, and to examine whether EmA-equivalent autoantibodies against TG2 can be demonstrated in the small bowel mucosa when absent in serum. PATIENTS: Serum EmA was studied in 177 biopsy- proven adult coeliac disease patients. Twenty patients with intestinal diseases served as non-coeliac controls; three had autoimmune enteropathy with villous atrophy. METHODS: Clinical manifestations, small bowel mucosal morphology, intraepithelial inflammation and TG2- specific extracellular IgA deposits were investigated in both serum EmA-negative and EmA-positive patients. RESULTS: Twenty-two IgA-competent coeliac disease patients were negative for serum EmA. Three of these had small bowel lymphoma. EmA-negative coeliac disease patients were older, had abdominal symptoms more often, and in their intestinal mucosa the density of gamma& [delta]+ IELs was lower than in EmA-positive patients; otherwise the histology was similar. All, also serum EmA- negative, coeliac disease patients, but none of the disease controls had gluten-dependent mucosal IgA deposits alongside TG2 in the small bowel mucosal specimens. In vivo deposited IgA was shown to be TG2- specific by its ability to bind recombinant TG2. CONCLUSIONS: Negative serum EmA might be associated with advanced coeliac disease. TG2-targeted autoantibodies were deposited in the small bowel mucosa even when absent in serum. This finding can be utilized in the diagnosis of seronegative coeliac disease when the histology is equivocal. It also seems to be helpful in differential diagnosis between autoimmune enteropathy and coeliac disease.
PMID: 16571636

Autoantibody targeting of brain and intestinal transglutaminase in gluten ataxia. PMID: 16476935 Feb 2006

OBJECTIVE: To investigate the presence of autoantibody deposition against type 2 tissue transglutaminase (TG2; a reliable marker of the whole spectrum of gluten sensitivity) in the jejunal tissue and brain of patients with gluten ataxia and in control subjects. METHODS: The authors evaluated jejunal biopsy samples from nine patients with gluten ataxia and seven patients with other causes of ataxia for the presence of TG2-related immunoglobulin deposits using double-color immunofluorescence. Autopsy brain tissue from one patient with gluten ataxia and one neurologically intact brain were also studied. RESULTS: IgA deposition on jejunal TG2 was found in the jejunal tissue of all patients with gluten ataxia and in none of the controls. The intestinal IgA deposition pattern was similar to that seen in patients with overt and latent celiac disease and in those with dermatitis herpetiformis. Widespread IgA deposition around vessels was found in the brain of the patient with gluten ataxia but not the control brain. The deposition was most pronounced in the cerebellum, pons, and medulla. CONCLUSIONS: Anti-tissue transglutaminase IgA antibodies are present in the gut and brain of patients with gluten ataxia with or without an enteropathy in a similar fashion to patients with celiac disease, latent celiac disease, and dermatitis herpetiformis but not in ataxia control subjects. This finding strengthens the contention that gluten ataxia is immune mediated and belongs to the same spectrum of gluten sensitivity as celiac disease and dermatitis herpetiformis.
PMID: 16476935

Small-bowel mucosal transglutaminase 2-specific IgA deposits in coeliac disease without villous atrophy: a prospective and randomized clinical study. PMID: 16036509 May 2005

OBJECTIVE: In coeliac disease, autoantibodies directed against transglutaminase 2 are produced in small-bowel mucosa, and they have been found to be deposited extracellularly. The aim of this study was to investigate whether such mucosal IgA deposits are important in the diagnostic work-up of early-stage coeliac disease without small-bowel mucosal villous atrophy. MATERIAL AND METHODS: Forty-one adults suspected of coeliac disease owing to increased density of mucosal gamma(delta)+ intraepithelial lymphocytes but normal villous morphology were randomized to gluten challenge or a gluten-free diet for 6 months. Clinically and histologically verified gluten dependency was compared with existence of small-bowel mucosal transglutaminase 2-specific extracellular IgA deposits and (coeliac disease-type) HLA DQ2 and DQ8; 34 non-coeliac subjects and 18 patients with classical coeliac disease served as controls. RESULTS: Of the 41 patients, 5 in the challenge group and 6 in the gluten-free diet group were clinically gluten sensitive; all 11 had HLA DQ2 or DQ8. Ten of these 11 patients showed transglutaminase 2-targeted mucosal IgA deposits, which were dependent on gluten consumption. Minimal IgA deposits were seen in only 3 out of 30 patients with suspected coeliac disease without any clinically detected gluten dependency. The deposits were found in all classical coeliac patients and in none of the non-coeliac control subjects. CONCLUSIONS: Clinically pertinent coeliac disease exists despite normal small-bowel mucosal villous architecture. Mucosal transglutaminase 2-specific IgA deposits can be utilized in detecting such patients with genetic gluten intolerance.
PMID: 16036509