IgA anti-epidermal transglutaminase autoantibodies: a sensible and sensitive marker for diagnosis of dermatitis herpetiformis in adult patients.

BACKGROUND: Dermatitis herpetiformis (DH) is a rare gluten-sensitive blistering itchy skin disease, strictly related to coeliac disease (CD). Direct immunofluorescence, demonstrating IgA granular deposits localized either in the dermal papillae or along the dermo-epidermal junction, is currently the gold standard for diagnosis of DH. It has been shown that DH immunocomplexes contain epidermal transglutaminase (eTG) and that sera from patients with DH contain antibodies specifically directed against eTG. OBJECTIVES: We studied the usefulness of serum eTG antibodies in discriminating between DH, CD and other gastrointestinal and dermatologic diseases. METHODS: eTG antibodies were tested in 308 adult patients' sera: 44 patients with untreated dermatitis herpetiformis (UDH), 99 patients with untreated coeliac disease (UCD), 70 dermatological controls and 95 gastrointestinal controls. RESULTS: In UDH eTG antibody levels were significantly higher than in DH patients on gluten-free diet, UCD, gastrointestinal controls and dermatological controls. In UCD eTG antibodies strongly correlated with tissue transglutaminase (tTG) antibodies, whereas in UDH no significant correlation was observed. CONCLUSION: Serum IgA eTG antibody determination can efficiently distinguish UDH from other dermatological itchy diseases and is highly sensitive to gluten-free diet.

The incidence of coeliac disease in adult first degree relatives.

BACKGROUND AND AIMS: Although prevalence of coeliac disease among first degree relatives of coeliac patients is well-known, only four studies are available about its incidence. We investigated whether first degree relatives found to be negative at a first serological screening can subsequently develop coeliac disease. PATIENTS AND METHODS: In the last 6 years, endomysial antibodies were tested in 158 adult first degree relatives referred to our coeliac out-patient clinic. After at least a year, negative subjects were offered a second testing. Sixty-three accepted. RESULTS: 130/158 first degree relatives tested negative initially. Although one of them had developed coeliac disease after the first testing, at the second testing none of the 63 endomysial antibody negative first degree relatives proved positive. Incidence of coeliac disease among first degree relatives was 1/64 in 51 months, 0.437% year (95%CI 0.05-2.62). An analysis of the sample size showed that 10,000 first degree relatives must be followed up to significantly reduce the CI. CONCLUSIONS: Although we confirmed the high prevalence of coeliac disease among first degree relatives (28/158, 17.7%), we found that the low incidence suggests that further studies are required to understand whether endomysial antibody negative first degree relatives need to be followed up.

Is a gluten-free diet necessary in patients with potential celiac disease?

Potential celiac disease is characterized by a normal duodenal mucosa despite high intraepithelial lymphocytes count and/or positive endomysial antibodies while on a gluten-containing diet. An agreement about the management of this condition is still lacking. A 68-year-old lady complaining of weight loss and epigastric pain was found to be affected by potential celiac disease. Although she maintained a gluten-containing diet, epigastric pain and weight loss disappeared. If she had started a gluten-free diet, the improvement would have been considered a demonstration of the beneficial effect of the diet. Potential celiac patients can be maintained on a gluten-containing diet providing they are closely followed up.

[The historical-scientific foundations of thalassotherapy: state of the art]. / Le basi storico-scientifiche della talassoterapia: stato dell'arte.

Throughout the ages the interest in the use of sea water in medicine has fluctuated from century to century and from nation to nation. In this paper, the historical development of sea medicine from the ancient Egyptians until the 20th century is given. The medical world has viewed it with different opinions, from very enthusiastic to extremely critical, and from beneficial to harmful. In the last decades, thalassotherapy is receiving renewed attention from many medical specialties and health tourists. The aim of this review is that of offer an update on the real therapeutic possibility of the thalassotherapy. However, the exact therapeutic potential of thalassotherapy still remains largely unknown. Better and more profound scientific evidence for its efficacy is therefore warranted, in particular for its effects on the musculoskeletal system and skin. The main researches belong to the activity of thalassotherapy and the clinic outcomes, namely in osteoarthritis patients, were referred.

Transglutaminase 2 in the enterocytes is coeliac specific and gluten dependent.

BACKGROUND: Tissue transglutaminase, the coeliac autoantigen, was shown to localise in the enterocytes of coeliac patients and controls. It was speculated that surface tissue transglutaminase has a role in the pathogenesis of coeliac disease. AIMS: To study localisation of tissue transglutaminase in different stages of coeliac disease and other enteropathies with and without villous flattening. METHODS: Immunofluorescent and immunoblotting assays were used. Duodenal cryostat sections from 23 coeliac patients (10 untreated, 8 treated, 5 potential) and 18 controls (2 autoimmune enteropathy and 16 normal duodenal mucosa) were incubated with an anti-tissue transglutaminase monoclonal antibody. Slides were blindly examined. RESULTS: The immunofluorescent assay showed that monoclonal antibody localised in the subepithelial layer, in the lamina propria, and in the pericryptal connective tissue of all samples. It also bound to surface enterocytes in 8/10 untreated, 1/8 treated, and 3/5 potential coeliac patients. None of the controls showed an epithelial distribution of tissue transglutaminase. Immunoblotting experiments performed in enterocytes freshly isolated from duodenal biopsy confirmed these findings. CONCLUSION: Epithelial distribution of tissue transglutaminase is specific for coeliac disease rather than due to a non-specific mucosal inflammation. Analysis of different stages of coeliac disease suggests that the epithelial distribution of tissue transglutaminase is gluten dependent.

Intraepithelial lymphocytes in the villous tip: do they indicate potential coeliac disease?

BACKGROUND: The counting of intraepithelial lymphocytes (IELs) in the villous tips of architecturally normal small bowel biopsy specimens was proposed as a method to measure mucosal infiltration in gluten sensitive patients. AIMS: To apply this straightforward method in duodenal biopsy specimens from patients affected by potential coeliac disease (PCD) to verify whether it can discriminate these patients from controls. METHODS: Paraffin wax embedded duodenal sections from 11 patients affected by PCD were stained with an antihuman CD3 antibody. Sections from 19 patients affected by treated coeliac disease (TCD) and 17 patients in whom coeliac disease was excluded were stained with the same antibody to serve as controls. The slides were examined blindly. IELs/20 enterocytes in five randomly chosen villous tips were counted. Patients affected by PCD were all on a gluten containing diet. They had an architecturally normal duodenal mucosa and were positive for endomysial antibody. Both TCD and non-coeliac controls were negative for endomysial antibody. RESULTS: The mean villous tip IEL scores were 4.6 (SD, 1.5; range, 1.4-7.8) in non-coeliac controls, 7.9 (SD, 4.0; range, 2.0-18.6) in TCD, and 9.2 (SD, 4.7; range, 5.8-21.8) in patients with PCD. The difference between PCD and non-coeliac controls was significant. CONCLUSIONS: This is a very simple and sufficiently reliable method to count IELs. In patients with an architecturally normal duodenal mucosa, the IEL count in villous tips helps to distinguish between patients with PCD and non-coeliac controls.

[Efficacy of mud-bath therapy with Mineral Water from the Sillene spring at Italy's Chianciano Spa for osteoarthritis of the knee: a clinical statistical study]. / Effcacia della fangobalneoterapia con Acqua Minerale Sillene (Terme di Chianciano, Italia) nell'osteoartrosi del ginocchio: uno studio clinico-statistico.

AIMS: Many previous researches showed clinical benefits, effects on inflammatory mediators and pain, immune system, hormones and on the diencephalic-pituitary-adrenal axis. Our study evalues the efficacy of mud-bath therapy with mineral water from the Sillene Spring at Italy's Chianciano Spa in patients with osteoarthritis of the knee. MATERIALS AND METHODS: In study we compared: physical examination of the knee joint, visual analogue scale (VAS) assessment of pain, and Lequesne Algo-functional Index. Tests were performed in 61 patients divided into 2 groups. The group A underwent three full cycles of mud-bath therapy over 1 year's time, the group B did not. An observational longitudinal study was also conducted on the patients of group A, before and after completion of the treatment protocol. Statistical analyses were based on use of Pearson's chi² test, Student's t tests for paired and unpaired data. RESULTS: The percentage of patients with no symptoms or mild symptoms was higher in group A than in group B (differences were highly significant); the mean value of VAS and the overall Lequesne indexes mean score reported in group A was significantly lower than that reported in group B. The same we observed comparing the clinical conditions of group A patients before and after mud-bath therapy. No adverse effects were observed in any of the patients in group A. CONCLUSIONS: The mud-bath therapy at Chianciano Spa significantly improves the clinical conditions of patients with knee osteoarthritis and significantly reduces the frequency and severity of symptoms and the disability they cause.

The prevalence and the causes of minimal intestinal lesions in patients complaining of symptoms suggestive of enteropathy: a follow-up study.

AIMS: Although they are non-specific, minimal intestinal lesions are at the end of the coeliac histological damage spectrum. To investigate whether minimal intestinal lesions in patients without endomysial antibodies are due to coeliac disease, their prevalence, causes and risk of evolving into frank coeliac disease were studied. METHODS: From January 2000 to December 2005, 645 duodenal biopsies were performed. In 209 patients, duodenal biopsies were performed independently of endomysial antibody results. Clinical data and HLA-typing of all the patients negative to endomysial antibodies but with minimal mucosal lesions were re-evaluated. Three years later, they were offered to be seen again, and further investigations were proposed. RESULTS: 14 out of 209 patients had minimal mucosal lesions and negative endomysial antibodies. Two patients were lost to follow-up; in 7/12 patients, symptoms and histological lesions were due to a different condition, not related to coeliac disease. In 11/12 patients, HLA-typing made diagnosis of coeliac disease very unlikely. Only one patient was on a gluten-free diet because of gluten-sensitive symptoms and was DQ2(+)/DQ8(+). CONCLUSIONS: Minimal duodenal lesions in patients negative to endomysial antibodies are rare and are likely to be due to conditions unrelated to coeliac disease.

Isolation and characterization of mutants of Arabidopsis thaliana with increased resistance to growth inhibition by indoleacetic acid-amino acid conjugates.

Two mutants of Arabidopsis thaliana that are resistant to growth inhibition by indole-3-acetic acid (IAA)-phenylalanine have been isolated. Both mutants were 2- to 3-fold more resistant than wild type to inhibition by IAA-phenylalanine, IAA-alanine, and IAA-glycine in root growth assays. The mutant icr1 (but not icr2) also shows some resistance to IAA-aspartate. Studies using 3H-labeled IAA-phenylalanine showed that the uptake of conjugate from the medium by icr1 was the same as wild type and was reduced by about 25% in icr2. No differences in hydrolysis of the exogenous conjugate were detected between the mutants and their wild-type parents. There was no significant metabolism of the IAA released from the [3H]IAA-phenylalanine, whereas exogenous [3H]IAA was rapidly metabolized to two unidentified products considerably more polar than IAA. Analysis of a cross between icr1 and icr2 indicated that these mutations were at distinct loci and that their effects were additive, and preliminary mapping data indicated that icr1 and icr2 were located at the top and bottom of chromosome V, respectively.

Endomysial and tissue transglutaminase antibodies in coeliac sera: a comparison not influenced by previous serological testing.

BACKGROUND: Since transglutaminase was shown to be the antigen of endomysial antibodies (EMA), it has become possible to screen for coeliac disease (CD) with an enzyme-linked immunosorbent assay (ELISA) for transglutaminase antibodies (TTA). However, it is possible that sera used to show that TTA are found in CD were obtained from patients diagnosed because they were positive for EMA. So, a comparison between EMA and TTA has not been possible so far. METHODS: EMA and TTA were tested in sera from 52 controls and 56 untreated CD patients, who had not undergone serological testing. Samples were tested for TTA with an ELISA kit. Based on the ROC analysis of a pilot study, results were considered as either positive, borderline, or negative. EMA were analysed by indirect immunofluorescence on monkey oesophagus. RESULTS: Forty-nine CD patients were positive for TTA, six borderline, one negative. Forty-four controls were negative, seven borderline, one positive. If we consider borderline results to be positive, sensitivity is 98.2% and specificity 84.6%. EMA were positive in 53 CD patients; the controls were all negative. Performing TTA in all cases and EMA only in the few TTA borderline cases (12.0%) would have a sensitivity of 94.6% and a specificity of 98.1%. CONCLUSIONS: This study is the first to compare TTA with EMA. Due to 100% specificity and high sensitivity, EMA seems to be the most accurate coeliac antibody. Conversely, TTA offer advantages in terms of sensitivity and simplicity. A satisfactory strategy is to use TTA first and then EMA to confirm the borderline results.