Serum Transglutaminase Research Articles

Indirect Markers of Intestinal Damage in IgA Nephropathy

Introduction: Presence of subclinical intestinal inflammation has repeatedly been shown in IgA nephropathy (IgAN) and the degree of histological inflammation has correlated with abnormal urinary findings. There is lack of noninvasive biomarkers evaluating the presence of subclinical intestinal damage in IgAN. We conducted this study hypothesizing that selected biomarkers regarded as indirect markers of intestinal damage could be elevated in IgAN. Methods: Eighty-five primary IgAN patients (median age 55 years, 54% men) participated in this single-center study in Tampere, Finland. None had end-stage kidney disease or previously diagnosed enteropathies. Celiac disease was excluded with serum transglutaminase 2 antibody (TG2Ab) and endomysial antibody tests and inflammatory bowel disease with fecal calprotectin. Intestinal damage was evaluated from sera with analyses of intestinal fatty-acid binding protein (I-FABP), soluble cluster of differentiation molecule 14 (sCD14), and lipopolysaccharide binding protein. Fourteen people suffering from dyspepsia and 15 healthy people served as controls. Results: I-FABP levels among IgAN patients were higher than in the healthy controls (median 830 pg/mL vs. 289 pg/mL, p < 0.001). Also, sCD14 was increased in IgAN patients compared to dyspepsia controls. Although TG2Ab levels were within the normal range among IgAN patients, they were higher than in the healthy controls (median 1.3 U/mL vs. 0.6 U/mL, p < 0.001). Conclusions: Elevated serum levels of I-FABP were present in primary IgAN patients without known enteropathies. Serum I-FABP may indicate the presence of subclinical intestinal damage. These findings encourage further investigation into the role of the intestine in the pathophysiology of IgAN.

Spinocerebellar Ataxia Type 35 Caused by a New TGM6 Variant: Video Documentation of a German Family.

Spinocerebellar Ataxia Type 35 Caused by a New TGM6 Variant: Video Documentation of a German Family.

Serum transglutaminase antibodies do not always detect the persistent villous atrophy in patients with celiac disease on a gluten-free diet.

Serum transglutaminase antibodies (tTGs) are used for celiac disease screening and to monitor celiac disease patients on a gluten-free diet (GFD). The need for histology of duodenal biopsies to assess mucosal healing after a GFD is still a matter of debate. We evaluated whether tTGs are adequate to detect the persistence of histological lesions of duodenal mucosa in celiac patients after a GFD. In total 253 patients with histological diagnosis of celiac disease according to Marsh criteria, both at the time of diagnosis (T0) and 18-24 months after starting a GFD (T2), were included. tTGs were evaluated both at T0 and T2; endomysial antibodies (EMAs) only at T0. At T0, 9.2% of patients had both tTG and EMA negative values, despite the evidence of duodenal lesions: 33.3% of Marsh 1, 14.3% of Marsh 2 and 5.2% of Marsh 3. At T2, tTGs were negative in 77.6% of patients: 82.2% of Marsh 0, 79.8% of Marsh 1, 70.0% of Marsh 2 and 59.1% of Marsh 3. At T2, approximately 60% of patients with the persistence of mucosal atrophy had negative tTGs. At T0, tTG median values were lower in patients with Marsh 1 and Marsh 2 than patients with Marsh 3 (P < 0.001), whereas no difference was found at T2 regardless of Marsh's grade (P = 0.4). The results of our study highlight how histologic evaluation of duodenal biopsies remains the gold standard for both celiac disease diagnosis and the evaluation of mucosal recovery after 18-24 months of a GFD.

Serum transglutaminase 2 activity as a potential biomarker of disease severity and response to omalizumab in chronic spontaneous urticaria

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No.2018R1A2B6009178) and Hallym University Research Fund 2017 (HURF-2017-76). Transglutaminase 2 (TG2) is expressed in mast cells and contributes to allergic asthma. We have previously reported that TG2 was associated with the pathogenesis of chronic spontaneous urticaria (CSU). The aim of this study is to investigate the clinical implication of serum TG2 levels in CSU. Patients with CSU (n=111), acute urticaria (AU, n=31), and normal controls (NC, n=45) were enrolled. TG2 activity in serum were measured by ELISA. Serum TG2 activity was serially measured in 9 patients with CSU in accordance with omalizumab treatment. Patients were divided by disease severity (mild, moderate, severe, very severe) which is defined by the treatment level from the guidelines for treatment of CSU. Student’s T-test and Wilcoxon signed-rank test were done for statistical analyses using SPSS, ver. 21 (SPSS Inc, Chicago, Illinois). TG2 activity was significantly higher in sera of CSU patients (132.8 ± 81.6 mU/mL) than AU (86.4 ± 57.8 mU/mL) and NC (70.0 ± 42.4 mU/mL). (P < 0.05, respectively), while Serum TG2 activity in AU was not significantly different from NC (P > 0.05). Serum TG2 activity in CSU patients was significantly increased according to disease severity (mild: 87.1 ± 66.3 mU/mL, moderate: 136.1 ± 64.0 mU/mL, severe: 159.7 ± 59.0 mU/mL, very severe: 222.1 ± 68.1 mU/mL, P < 0.0001). Initial TG2 activity was significantly decreased after omalizumab treatment (P < 0.05). Serum TG2 activity represents disease severity of CSU. Serum TG2 activity could be a useful marker of disease severity and treatment response of CSU.

Tests for Serum Transglutaminase and Endomysial Antibodies Do Not Detect Most Patients With Celiac Disease and Persistent Villous Atrophy on Gluten-free Diets: a Meta-analysis

Tests to measure serum endomysial antibodies (EMA) and antibodies to tissue transglutaminase (tTG) were developed to screen for celiac disease in patients consuming gluten. However, they are commonly used to monitor patients on a gluten-free diet (GFD). We conducted a meta-analysis to assess the sensitivity and specificity of tTG IgA and EMA IgA assays in identifying patients with celiac disease who have persistent villous atrophy despite a GFD. We searched PUBMED, EMBASE, BIOSIS, SCOPUS, clinicaltrials.gov, Science Citation Index, and Cochrane Library databases through November 2016. Inclusion criteria were studies of subjects with biopsy-confirmed celiac disease, follow-up biopsies, and measurement of serum antibodies on a GFD, biopsy performed on subjects regardless of symptoms, or antibody test results. Our analysis excluded subjects with refractory celiac disease, undergoing gluten challenge, or consuming a prescribed oats-containing GFD. Tests were considered to have positive or negative findings based on manufacturer cut-off values. Villous atrophy was defined as a Marsh 3 lesion or villous height:crypt depth ratio below 3.0. We constructed forest plots to determine the sensitivity and specificity of detection for individual studies. For the meta-analysis, a bivariate random effects model was used to jointly model sensitivity and specificity. Our search identified 5408 unique citations. Following review of abstracts, 442 articles were reviewed in detail. Only 26 studies (6 of tTG assays, 15 of EMA assays, and 5 of tTG and EMA assays) met our inclusion criteria. The most common reason studies were excluded from our analysis was inability to cross-tabulate histologic and serologic findings. The serum assays identified patients with persistent villous atrophy with high levels of specificity: 0.83 for the tTG IgA assay (95% CI, 0.79-0.87) and 0.91 for the EMA IgA assay (95% CI, 0.87-0.94). However, they detected villous atrophy with low levels of sensitivity: 0.50 for the tTG IgA assay (95% CI, 0.41-0.60) and 0.45 for the EMA IgA assay (95% CI, 0.34-0.57). The tests had similar levels of performance inpediatric and adult patients. In a meta-analysis of patients with biopsy-confirmed celiac disease undergoing follow-up biopsy on a GFD, we found that tests for serum tTG IgA and EMA IgA levels had low sensitivity (below 50%) in detection of persistent villous atrophy. We need more-accurate non-invasive markers of mucosal damage in children and adults with celiac disease who are following aGFD.

Ethnic differences in coeliac disease autoimmunity in childhood: the Generation R Study

ObjectiveThe aim was to identify whether ethnic differences in coeliac disease autoimmunity (CDA) in children at 6 years of age exist, and when present, to evaluate how these differences may...

Generation R birth cohort study shows that specific enamel defects were not associated with elevated serum transglutaminase type 2 antibodies.

Coeliac disease can induce specific enamel defects (SED), but little is known about the consequences of antitissue transglutaminase (TG2A) autoimmunity. We investigated whether TG2A positivity in children and their mothers was associated with SED in the primary dentition. Maternal and child serum immunoglobulin A-TG2A levels were measured as part of the Generation R prospective cohort study. Clinical oral photographs of the primary dentition were taken, and SED and caries were recorded. We performed logistic regression analysis. We analysed data on 4775 mothers and 4233 children (median age of 6.2 ± 0.5 years). SED and caries were not associated with maternal TG2A levels. The 59 TG2A-positive children tended to have more SED, particularly the 31 in the strongly positive subgroup, with odds ratio of 1.72 and 2.29, respectively. A positive linear trend was observed between higher TG2A levels and paediatric SED (p = 0.04), but this became nonsignificant after adjusting for ethnic and socio-economic background. No difference in caries was found between the groups. TG2A did not play an independent role on SED in the primary dentition during pregnancy and childhood, and the relationship may be explained by ethnic and socio-economic background.

Serum transglutaminase 3 antibodies correlate with age at celiac disease diagnosis

BackgroundTransglutaminase (TG)2 is the autoantigen in celiac disease, but also TG3 antibodies have been detected in the serum of celiac disease patients. AimsTo investigate the correlations between serum TG3 antibodies and clinical and histological manifestations of celiac disease and to assess gluten-dependency of TG3 antibodies. MethodsCorrelations between serum TG3 antibody levels measured from 119 adults and children with untreated coeliac disease and the demographic data, clinical symptoms, celiac antibodies, histological data and results of laboratory tests and bone mineral densities were tested. TG3 antibodies were reinvestigated in 97 celiac disease patients after 12 months on a gluten-free diet (GFD). ResultsTG3 antibody titers were shown to correlate with the age at celiac disease diagnosis. Further, negative correlation with TG3 antibodies and intestinal γδ+ cells at diagnosis and on GFD was detected. Correlations were not detected with the clinical manifestation of celiac disease, TG2 or endomysial autoantibodies, laboratory values, severity of mucosal villous atrophy, associated diseases or complications. TG3 antibody titers decreased on GFD in 56% of the TG3 antibody positive patients. ConclusionSerum TG3 antibody positivity in celiac disease increases as the diagnostic age rises. TG3 antibodies did not show similar gluten-dependency as TG2 antibodies.

Identification of a serum transglutaminase threshold value for the noninvasive diagnosis of symptomatic adult celiac disease patients: a retrospective study

A celiac disease (CD) diagnosis is based on duodenal histology, with the exception of children showing anti-tissue transglutaminase (anti-tTG) serum levels exceeding ten times the cut-off. Our aim was to reproduce this simplified approach in adults, identifying an anti-tTG threshold value useful to diagnose CD without endoscopic procedures. A total of 671 adult CD patients were subjected to blood sampling to determine anti-tTG serum levels, as well as to endoscopy with biopsy to perform duodenal histology. The anti-tTG serum levels/cut-off ratio was compared with the degree of duodenal lesions. Anti-tTG serum levels/cut-off ratio determined in patients with type IIIc was significantly higher than that measured in patients with type IIIb (p<0.001), IIIa (p<0.001), II (p<0.05) and 0 (p<0.001) of Marsh-Oberhuber histological classification. A significant correlation (r=0.297, p<0.0001) was found between the anti-tTG serum levels/cut-off ratio and the degree of duodenal lesions. The anti-tTG serum levels/cut-off ratio was classified as an accurate parameter (AUC=0.715, p<0.0001), with the best diagnostic performance obtained considering the threshold value >3.6 (sensitivity=76.8%, PPV=97.2%). The anti-tTG serum levels/cut-off ratio correlates with the degree of duodenal lesions and, if used with the threshold value >3.6, could avoid endoscopy with biopsy in about 75% of seropositive adults waiting for CD diagnosis. However, since this procedure could also imply CD diagnosis in almost 3% of seropositive patients with normal villous architecture, a consensus opinion is needed to suggest its use in the diagnosis of adult CD.

Biochemical markers to the protective effects of Fructus Piperis Longi extract on Hepatic encephalopathy in rats

The present study was designed to elucidate the protective effect of subsequent pretreatment withFructus Piperis Longi extract in liver and brain tissue of experimental rats exposed to Hepaticencephalopathy induced by intraperitoneal administration of TAA. Plf extract (50 mg/kg) was force-fedto rats every day, 7 days before administration of Thioacetamide. Thioacetamide 200 mg/kg wasintraperitoneally administered to rats twice per week for four weeks. Administration of Plfext wasextended during Thioacetamide. After 4 weeks, animals were sacrificed. Biochemical parameters inserum and homogenized liver and brain were tested. A significant increase in serum transglutaminase,alkaline phosphatase and gamma glutamyl transferase activity and plasma ammonia, a significantdecrease in serum albumin and total protein was recorded in the liver of Thioacetamide-treated rats.Significant increases in liver and brain lipid peroxides associated to significant decreases of liver andbrain reduced glutathione concentration and catalase activities were also recorded. Administration ofPlfext treatment reduced the severity of liver fibrosis and oxidative damage which was substantiated byimprovement of liver function detected by a decrease in serum aspartate amino transaminase, alanineaminotransferase, alkaline phosphatase, gamma glutamyl transferase activities and increase in totalprotein and Albumin. It was concluded that treatment of the ethanolic extract of Fructus Piperis Longienhance Liver and brain parameter and enhanced antioxidant activities of liver and brain.

Contribution of celiac disease autoantibodies to the disease process

Evaluation of: Teesalu K, Panarina M, Uibo O, Uibo R, Utt M. Autoantibodies from patients with celiac disease inhibit transglutaminase 2 binding to heparin/heparan sulfate and interfere with intestinal epithelial adhesion. Amino Acids doi:10.1007/s00726-011-1020-1 (2011) (Epub ahead of print).Transglutaminase 2 is a multifunctional protein involved in cellular adhesion. Moreover, transglutaminase 2 has been identified as the autoantigen in celiac disease, and in untreated celiac disease, in addition to being present in the serum, the transglutaminase 2-targeted autoantibodies are bound to their antigen in the basement membrane underlining the small-bowel mucosal epithelium. Furthermore, the disease-specific transglutaminase 2-targeted autoantibodies have been experimentally shown to exert various biological effects on different cell types. Using Caco-2 intestinal epithelial cells, it has now also been demonstrated that serum transglutaminase 2-targeted autoantibodies from untreated celiac patients inhibit the adhesion of these cells. These findings provide an important direction for future research to improve our general understanding of celiac disease pathogenesis and especially the role of the disease-specific autoantibodies during the progression of the disorder.

Does celiac disease trigger autoimmune thyroiditis?

Autoimmune thyroiditis has increased prevalence in patients with celiac disease and vice versa. new research suggests that serum transglutaminase 2 autoantibodies, which are present in patients with celiac disease, might have a role in the development of thyroid dysfunction.

Performance of a new rapid whole blood coeliac test in adult patients with low prevalence of endomysial antibodies

Background In coeliac disease endomysial and transglutaminase autoantibodies are directed against the human autoantigen, transglutaminase. The conventional coeliac antibody tests are performed from serum samples in centralized laboratories. Aims To evaluate a rapid and easy immunoglobulin A-class whole blood point-of-care test and its commercial application, the Biocard test, in coeliac autoantibody detection. Methods In the whole blood point-of-care test transglutaminase is liberated from the red blood cells by haemolysis. Transglutaminase antibodies, if present, complex with the liberated antigen, and are visualized. Altogether 51 biopsy-proven untreated coeliac adult patients, 48 of the same patients after treatment, and 36 controls were tested. The point-of-care test results were compared with serum endomysial and transglutaminase antibody and Biocard test results and histology. Results The whole blood point-of-care test was as sensitive (82%) as the serum endomysium test (80%) in detecting untreated coeliac disease while the serum transglutaminase antibody test was superior (88%). The tests had 100% specificity. A positive point-of-care test result seroconverted or the test reaction weakened in 90% of the treated coeliac patients. Biocard test-positive were 22 of the 24 tested untreated coeliac patients. Biocard test-negative were 15 of 19 controls. Conclusions The whole blood rapid tests are as reliable as the conventional serological tests in detecting untreated coeliac disease and in coeliac disease diet monitoring.

Serum transglutaminase correlates with endoscopic and histopathologic grading in patients with ulcerative colitis.

Factor XIIIa, a circulating form of transglutaminase, plays a key role in intestinal mucosal repair. We found that transglutaminase levels are decreased in serum of patients with inflammatory bowel diseases and demonstrated in a rat model of chronic colitis that serum transglutaminase is closely related to the severity of intestinal damage. We aimed, therefore, to correlate serum transglutaminase levels with standard endoscopic and histopathologic grading systems in patients affected by ulcerative colitis (UC). In 249 patients with UC, we assayed serum transglutaminase activity by a radioenzymatic method and measured clinical activity index (CAI) according to modified Rachmilewitz's criteria. In a subset of 82 patients undergoing colonoscopy, endoscopic and histologic indices were studied. Biopsy specimens were also taken from 28 patients to measure myeloperoxidase (MPO) as a marker of mucosa inflammation. Serum transglutaminase levels significantly correlated with the CAI scoring (r = -0.63; P < 0.01); likewise serum transglutaminase showed the best correlation with endoscopic (r = -0.71; P < 0.001) and histologic (r = -0.79; P < 0.001) scores. Myeloperoxidase activity was significantly higher in patients with active UC than those in remission (P < 0.01), showing a significant correlation with serum transglutaminase levels (r = -0.68; P < 0.01). Immunohistochemistry showed factor XIIIa localization in the extracellular matrix of damaged mucosa. In conclusion, these results suggest that transglutaminase assay can be useful in managing UC as a serological, noninvasive indicator of intestinal mucosal status.

Factor XIII Improves Gastric Stress Lesions in Rats

Background/Aims: Tissue transglutaminase has been reported to be involved in the healing of experimental gastric ulcer; nevertheless, other type(s) of transglutaminase could be involved. The present experiments aimed at examining whether plasma transglutaminase (factor XIIIa) contributes to such healing and at evaluating whether factor XIII supplementation improves gastric mucosal lesions. Methods: The healing effect of 200 U/kg of factor XIII administered intravenously was examined using a water immersion restraint rat model of stress gastric damage. The rats were sacrified 0, 2, 4, and 12 h after stress. The gastric mucosa was examined macroscopically and microscopically, and the transglutaminase activities were assayed in serum and gastric mucosa. Factor XIIIa and tissue transglutaminase protein levels in the gastric mucosa were analyzed by immunoblot. Immunohistochemistry was used to identify the location of tissue transglutaminase, factor XIIIa, and fibronectin in the gastric mucosa. Results: The transglutaminase activity, reduced by stress in the gastric mucosa, increased up to 12 h after stress, peaking at 4 h, when the ulcer index significantly decreased. The serum transglutaminase level was low at all time points. Exogenous administration of factor XIII allowed a faster reduction of the ulcer index that was coincident with an increased transglutaminase activity in the mucosa. Both tissue transglutaminase and factor XIIIa protein levels were reduced by 6 h of stress and increased after factor XIII administration. Immunohistochemistry showed a colocalization of both factor XIIIa and tissue transglutaminase with fibronectin in the extracellular matrix of the damaged area. Conclusions: Two forms of transglutaminase are involved in the healing of stress-induced gastric erosions, and factor XIII administration allows faster gastric mucosa healing.

Role of tissue transglutaminase in celiac disease.

Role of tissue transglutaminase in celiac disease.

Recombinant factor XIII improves established experimental colitis in rats.

Factor XIII (FXIII) is the plasma-borne transglutaminase involved in fibrin clot stabilization and wound healing. FXIII levels in the plasma of patients with inflammatory bowel diseases are lower than normal and there is a significant inverse correlation of FXIII levels with clinical severity. Moreover, uncontrolled studies report beneficial effects of FXIII supplementation in patients resistant to conventional therapies. We investigated the effects of intravenous recombinant FXIII (rFXIII) treatment in experimentally induced rat colitis to verify that FXIII was the active agent in plasma FXIII concentrates and to better understand the potential therapeutic use of this protein. Colitis was induced by instillation of 12% 2.4,6-trinitrobenzenesulfonic acid (TNBS) in 50% ethanol into the colon of male Wistar rats. Rats were treated with 0.65 mg/kg rFXIII or vehicle (intravenously) daily for 10 days. Treatment was started either immediately after TNBS/EtOH instillation (to evaluate effects on developing lesions) or seven days later (to evaluate effects on established lesions). In both cases rats were killed either immediately after the end of treatment (to evaluate immediate effects) or 17 days later (to evaluate long-lasting effects). The effects of rFXIII were compared to positive (5-amino-2-hydroxybenzoic acid) control over a 35-day time course. The severity of lesions was determined by colon weight and macroscopic and histologic scores. Transglutaminase activity was measured in both colon tissue and serum. rFXIII treatment reduced lesion severity significantly not only in developing but also in established lesions. Improvements in healing persisted at least 18 days after treatment was discontinued. Serum and tissue transglutaminase levels were restored by rFXIII treatment. In conclusion, pure rFXIII is as effective as plasma FXIII concentrates in a rat model of experimental colitis. In addition, rFXIII significantly improves the healing of preexisting lesions, a characteristic useful in treatment of human inflammatory bowel diseases.

SERUM TRANSGLUTAMINASE IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE

21 Background: The clinical activity of inflammatory bowel diseases(IBD) is based on clinical and laboratory findings that do not always reflect the pathogenic processes taking place in the intestine. There is evidence that Factor XIIIa, a plasma born transglutaminase (TG), plays a key role in the extracellular matrix assembly in damaged tissue following various intestinal injuries. We previously found that TG levels are decreased in serum of adult patients with IBD and demonstrated in a rat model of chronic colitis that serum TG is closely related to the severity of intestinal mucosal damage.Aims: The aim of this study was to extend our findings to children and to examine whether serum TG levels are related to the endoscopic activity index in children with IBD. Patients/Methods: Serum was collected from 16 children with Crohn's disease (mean age, 12.2±3 years; range, 8-17); from 11 children with ulcerative colitis (mean age, 10.4±3.3 years; range, 9-15); and from 9 age-matched healthy controls (mean age, 8±3.4 years; range, 5-16). Besides scoring clinical parameters, the disease activity of each patient was endoscopically evaluated as inactive(0-3), milde/moderate (3-5) or severe (5-10) scoring on a 0-2 scale the erythema, friability, granularity erosions and ulcerations. Serum TG activity was assayed by a radioenzymatic method. Results: Serum TG was significantly lower in patients with active disease compared with inactive disease or normal subjects (0.66±0.17 vs 1.34±0.62, p<0.001, and 0.66±0.17 vs 1.36±0.40, p<0.001; respectively). Serum TG showed a negative correlation with endoscopic scores both in children with Crohn's disease (r = -0.77, p<0.001) and ulcerative colitis (r = -0.74, p<0.01). Conclusions: These data raise the possibility that TG assay may prove useful in management of IBD in children as a new serological non-invasive indicator of intestinal mucosal status.

Serum transglutaminase correlates with endoscopical and histopathological grading in patients with ulcerative colitis

Serum transglutaminase correlates with endoscopical and histopathological grading in patients with ulcerative colitis

Transglutaminases in Crohn's disease.

Transglutaminases are a family of Ca-dependent enzymes involved in various biological events. Circulating transglutaminase (factor XIIIa) is decreased in blood of patients with inflammatory bowel diseases. There is evidence that factor XIIIa and tissue type transglutaminase, present in cell cytosol, bind to various proteins of the extracellular matrix. This study examined the value of serum transglutaminase assay in the treatment and follow up of Crohn's disease and then investigated the intestinal location of both forms of transglutaminases by immunohistochemistry in normal and abnormal tissues. Serum transglutaminase activity was assayed in 36 patients with active Crohn's disease (CDAI > 150). Eighteen patients were studied prospectively from relapse into remission. A significant inverse correlation (p < 0.001) was found between circulating transglutaminase and Crohn's disease activity index; a correlation was also found between serum transglutaminase and serum orosomucoid (p < 0.01) and C reactive protein (p < 0.01). Patients were prospectively studied until clinical remission showed improvement in both their CDAI score mean (SD) (230 (46) to 72 (34), p < 0.01) and transglutaminase activity mean (SD) (0.61 (0.12) to 0.93 (0.13) mU/ml, p < 0.01). The immunohistochemistry assessment showed a colocalisation of factor XIIIa and tissue transglutaminase to the extracellular matrix of damaged tissues. In conclusion, these data confirm the value of serum transglutaminase assay as marker of Crohn's disease activity, extend the utility of serum transglutaminase assay to follow up of the disease, and emphasised the role of different types of transglutaminases in extracellular matrix assembly in the damaged tissues.