Autoantibodies related to ataxia and other central nervous system manifestations of gluten enteropathy

Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease,immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following.We focused on the anti-gliadin antibodies,antibodies to different isoforms of tissue transglutaminase(TG)(anti-TG2,3,and 6 antibodies),anti-glycine receptor antibodies,anti-glutamine acid decarboxylase antibodies,anti-deamidated gliadin peptides antibodies,etc.Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction,presented as different neurological disorders.We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.

Transglutaminase 2 serves as a pathogenic hub gene of KRAS mutant colon cancer based on integrated analysis

BACKGROUND Colon cancer is acknowledged as one of the most common malignancies worldwide,ranking third in United States regarding incidence and mortality.Notably,approximately 40%of colon cancer cases harbor oncogenic KRAS mutations,resulting in the continuous activation of epidermal growth factor receptor signaling.AIM To investigate the key pathogenic genes in KRAS mutant colon cancer holds considerable importance.METHODS Weighted gene co-expression network analysis,in combination with additional bioinformatics analysis,were conducted to screen the key factors driving the progression of KRAS mutant colon cancer.Meanwhile,various in vitro experiments were also conducted to explore the biological function of transglutaminase 2(TGM2).RESULTS Integrated analysis demonstrated that TGM2 acted as an independent prognostic factor for progression-free survival.Immunohistochemical analysis on tissue microarrays revealed that TGM2 was associated with an elevated probability of perineural invasion in patients with KRAS mutant colon cancer.Additionally,biological roles of the key gene TGM2 was also assessed,suggesting that the downregulation of TGM2 attenuated the proliferation,invasion,and migration of the KRAS mutant colon cancer cell line.CONCLUSION This study underscores the potential significance of TGM2 in the progression of KRAS mutant colon cancer.This insight not only offers a theoretical foundation for therapeutic approaches but also highlights the need for additional clinical trials and fundamental research to support our preliminary findings.

Autoantibodies in chronic hepatitis C: A clinical perspective

Non-organ-specific autoantibodies and thyroid autoantibodies have been frequently found in chronic carriers of hepatitis C virus(HCV). With respect to endomysial antibodies and tissue transglutaminase, it is controversial whether the prevalence of glutenrelated seromarkers is higher in patients with HCV. In such cases, in addition to acknowledging any currently existing autoimmune disease, recognizing the risk of the patient developing an autoimmune disease during interferon(IFN)-based treatment must be a principle concern. From a clinical point-of-view, the presence of autoantibodies arouses suspicion that an autoimmunedisease may be present or may be precipitated by IFNbased HCV treatment. In this paper, we review the prevalence of autoantibodies in individuals with hepatitis C, the clinical significance of these autoantibodies, and the approach recommended for such situations.

Effects of Nicotinamide on Mouse Skin Tumor Development and Its Mode of Action

Nicotinamide (NA), a naturally occuring vitamin and a protease inhibitor, has been shown to be effective in treating some skin ailments. It inhibits cell proiferaion and induces cell differentiation. This report shows the effects of NA on mouse skin tumor development and on the critical events involved in this process. NA reduced tumor growth, inhibited the 12-O-tetradecanoylphorbol-13-acetate (TPA) induced ornithine decarboxylase activity, but induced the transglutaminare activity which was inhibited by TPA under different experimental conditions.The effects of NA on ornithine decarboxylare (ODC) and transglutaminase (TG) indicated that nicotinamide (NA) probably programmmed the cells for their death in the natural course of time, i.e. programed cell death. This observation indicates that NA might be a better agent for the detailed study and for the better use in prevention of cancer alone or in combination with other drugs.

Transglutaminase inhibition:A therapy to protect cells from death in neurodegeneration?

Transglutaminases(TGs;E.C.2.3.2.13)are ubiquitous enzymes which catalyze post-translational modifications of proteins.TGs and TG-catalyzed post-translational modifications of proteins have been shown to be involved in the molecular mechanisms responsible for several human diseases.In particular,TG activity has been hypothesized to also be involved also in the molecular mechanisms responsible for human neurodegenerative diseases.In support of this hypothesis,Basso et al recently demonstrated that the TG inhibition protects against oxidative stress-induced neuronal death,suggesting that multiple TG isoforms participate in oxidative stress-induced cell death and that nonselective TG isoform inhibitors will be most effective in fighting oxidative death in neurological disorders.In this commentary,we discuss the possible molecular mechanisms by which TG activity could be involved in the pathogenesis of neurological diseases,with particular reference to neurodegenerative diseases,and the possible involvement of multiple TG isoforms expressed simultaneously in the nervous system in these diseases.Moreover,therapeutic strategies based on the use of selective or nonselective TG inhibitors for the amelioration of thesymptoms of patients with neurological diseases,characterized by aberrant TG activity,are also discussed.

Physio-pathological roles of transglutaminase-catalyzed reactions

Transglutaminases(TGs) are a large family of related and ubiquitous enzymes that catalyze post-translational modifications of proteins.The main activity of these enzymes is the cross-linking of a glutaminyl residue of a protein/peptide substrate to a lysyl residue of a protein/peptide co-substrate.In addition to lysyl residues,other second nucleophilic co-substrates may include monoamines or polyamines(to form mono-or bi-substituted/crosslinked adducts) or-OH groups(to form ester linkages) .In the absence of co-substrates,the nucleophile may be water,resulting in the net deamidation of the glutaminyl residue.The TG enzymes are also capable of catalyzing other reactions important for cell viability.The distribution and the physiological roles of TG enzymes have been widely studied in numerous cell types and tissues and their roles in several diseases have begun to be identified."Tissue" TG(TG2) ,a member of the TG family of enzymes,has definitely been shown to be involved in the molecular mechanisms responsible for a very widespread human pathology:i.e.celiac disease(CD) .TG activity has alsobeen hypothesized to be directly involved in the pathogenetic mechanisms responsible for several other human diseases,including neurodegenerative diseases,which are often associated with CD.Neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease,supranuclear palsy,Huntington's disease and other recently identified polyglutamine diseases,are characterized,in part,by aberrant cerebral TG activity and by increased cross-linked proteins in affected brains.In this review,we discuss the physio-pathological role of TG-catalyzed reactions,with particular interest in the molecular mechanisms that could involve these enzymes in the physio-pathological processes responsible for human neurodegenerative diseases.

谷氨酰胺转氨酶热稳定剂优化

谷氨酰胺转氨酶(Transglutaminase,TGase)能够催化蛋白质分子发生交联,被广泛应用于食品、医药和纺织等领域。为提高其热稳定性,研究了糖、盐及醇类等稳定剂对TGase在55℃下的半衰期[t_(1/2)(55℃)]的影响。结果表明,山梨醇、小麦蛋白、Na Cl和葡萄糖能延长TGase的t_(1/2)(55℃)。在此基础上进行正交实验,获得最佳的稳定剂配方:山梨醇50 g/L、小麦蛋白50 g/L、Na Cl 50 g/L、葡萄糖50 g/L。在该复合稳定剂保护下,TGase的t_(1/2)(55℃)和最适反应温度较对照(无稳定剂)分别提高59.73倍和10℃;室温(25℃)储存80 d的残余酶活率为73.84%,较对照提高62.79%。此研究结果将促进TGase的生产改进和应用拓展。

南极磷虾肉糜制作研发

为开发南极磷虾食品,开展南极磷虾肉糜制作研究。研究采用谷氨酰胺转氨酶、组织化植物蛋白与南极磷虾肉糜进行反应,考察NaCl、CaCl2以及反应时间对凝胶的影响;结果表明:添加2%NaCl,4%组织化植物蛋白,0.5%转谷氨酰胺酶、0.1%CaCl2充分混匀,于20℃下放置2h,制备得到的虾肉糜结构紧密,凝胶强度高,同时在外观上色泽红润,并通过食品质量安全检测。综上所述,该研发技术,可以为南极磷虾肉糜开发与生产起到理论指导作用。

Novel method for extracting exosomes of hepatocellular carcinoma cells

AIM:To develop a novel method for the rapid and efficient extraction of exosomes secreted by tumor cells.METHODS:Unlike the traditional extraction method,the supernatants of cell cultures were concentrated,and the exosomes were isolated promptly and effectively using a novel nanomaterial called ExoQuick.Coomassie brilliant blue staining was used for protein quantification,and the morphology of the exosomes extracted by both methods was visualized by transmis-sion electron microscopy.Exosome marker proteins were detected by Western blot analysis.Two potential hepatoma-associated proteins,tissue transglutaminase2(TGM2)and annexin A2,were analyzed.RESULTS:The exosomes separated by the new extraction assay based on the nanomaterial were discshaped,intact vesicles with lipid bilayer membranes.They were approximately 30-100 nm in diameter,which is similar to the diameter of exosomes isolated by the traditional method.The protein concentration of exosomes extracted by the new method was approximately780μg/108 cells,and therefore,it was 19 times higher than that of exosomes extracted in the traditional manner.There were differences between the total proteins of Huh-7 cells and the exosomal proteins.Typical exosome proteins,such as the transmembrane protein CD63 and heat shock protein 70,were confirmed.Two potential hepatoma-associated proteins were also identified.TGM2 was first found to exist in the exosomes of human liver cancer cells,but annexin A2 was not secreted into exosomes.CONCLUSION:The new extraction method based on the nanomaterial is quick and efficient.The cancerassociated protein TGM2 can be secreted through an exosome-mediated non-classical secretion pathway,and it may be a valuable tumor marker.

Celiac disease serology in patients with different pretest probabilities: Is biopsy avoidable?

AIM: To establish the diagnostic performance of sev-eral serological tests, individually and in combination, for diagnosing celiac disease (CD) in patients with different pretest probabilities, and to explore potential se- rological algorithms to reduce the necessity for biopsy. METHODS: We prospectively performed duodenal biopsy and serology in 679 adults who had either high risk (n = 161) or low risk (n = 518) for CD. Blood samples were tested using six assays (enzyme-linked immunosorbent assay) that detected antibodies to tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP). RESULTS: CD prevalence was 39.1% in the high-risk population and 3.3% in the low-risk group. In high-risk patients, all individual assays had a high diagnostic efficacy [area under receiving operator characteristic curves (AU ROC): 0.968 to 0.999]. In contrast, assays had a lower diagnostic efficacy (AU ROC: 0.835 to 0.972) in the low-risk group. Using assay combinations, it would be possible to reach or rule out diagnosis of CD without biopsy in 92% of cases in both pretest populations. We observed that the new DGP/tTG Screen assay resulted in a surplus compared to more conventional assays in any clinical situation. CONCLUSION: The DGP/tTG Screen assay could be considered as the best initial test for CD. Combinations of two tests, including a DGP/tTG Screen, might be able to diagnose CD accurately in different clinical scenarios making biopsy avoidable in a high proportion of subjects.

Extracellular quality control in the epididymis

The epididymal lumen represents a unique extracellular environment because of the active sperm maturation process that takes place within its confines. Although much focus has been placed on the interaction of epididymal secretory proteins with spermatozoa in the lumen, very little is known regarding how the complex epididymal milieu as a whole is maintained, including mechanisms to prevent or control proteins that may not stay in their native folded state following secretion. Because some misfolded proteins can form cytotoxic aggregate structures known as amyloid, it is likely that control/surveillance mechanisms exist within the epididymis to protect against this process and allow sperm maturation to occur. To study protein aggregation and to identify extracellular quality control mechanisms in the epididymis, we used the cystatin family of cysteine protease inhibitors, including cystatin-related epididymal spermatogenic and cystatin C as molecular models because both proteins have inherent properties to aggregate and form amyloid. In this chapter, we present a brief summary of protein aggregation by the amyloid pathway based on what is known from other organ systems and describe quality control mechanisms that exist intracellularly to control protein misfolding and aggregation. We then present a summary of our studies of cystatinrelated epididymal spermatogenic （CRES） oligomerization within the epididymal lumen, including studies suggesting that transglutaminase cross-linking may be one mechanism of extracellular quality control within the epididymis. （Asian J Androl 2007 July; 9： 500-507）

Calcium Glucarate Prevents Tumor Formation in Mouse Skin

Objective Calcium Glucarate (Cag), Ca salt of D-glucaric acid is a naturally occurring non-toxic compound present in fruits, vegetables and seeds of some plants, and suppress tumor growth in different models. Due to lack of knowledge about its mode of action its uses are limited in cancer chemotherapy thus the objective of the study was to study the mechanism of action of Cag on mouse skin tumorigenesis. Methods We have estimated effect of Cag on DMBA induced mouse skin tumor development following complete carcinogenesis protocol. We measured, epidermal transglutaminase activity (TG), a marker of cell differentiation after DMBA and/or Cag treatment and [3H] thymidine incorporation into DNA as a marker for cell proliferation. Results Topical application of Cag suppressed the DMBA induced mouse skin tumor development. Topical application of Cag significantly modifies the critical events of proliferation and differentiation TG activity was found to be reduced after DMBA treatment. Reduction of the TG activ

Development and Physical Properties of Film of Wheat Gluten Cross-linked by Transglutaminase

Films were developed from the modified wheat glutens by microbial transglutamina se(MTGase, [E/S]=10u/g,15u/g and 20u/g) in order to improve physical and barri er properties of the films.Glycerol was used as a plasticizer.The films prepared from the modified-glutens by MTGase show a lower elongation at break(E) and a water vapor permeability(WVP), and a higher tensile strength(TS) than the nati ve gluten films.When the modified gluten films by different concentrations of MT Gase are immersed in water at 25℃,their weight losses decreased significantly, and their water resistance increases obviously as expected, compared with the c ontrol gluten films. Moreover, an addition of glycerol as plasticizer greatly mo dified water vapor barrier and mechanical properties of the films.

May the assessment of baseline mucosal molecular pattern predict the development of gluten related disorders among microscopic enteritis?

AIM To evaluate mucosal baseline m RNA expression of tissue transglutaminase 2(t TG2), interferon gamma(IFNγ), toll-like receptor 2(TLR2) and Myeloid Differentiation factor 88(MyD 88) in patients with microscopic enteritis(ME).METHODS We retrospectively enrolled 89 patients with ME of different etiology, which was defined within a 2-year mean period of follow-up. Baseline histological examination was performed on Hematoxylin-Eosin stained sections and CD3 lymphocyte immunohistochemistry was used for intraepithelial lymphocyte count(IELs). ME was defined according to the criteria of Bucharest Consensus Conference. For each patient, formalin embedded biopsy samples of the duodenum referred to the period of ME diagnosis were retrieved. Real-time polymerase chain reaction(RT-PCR) was used to detect the amount of mR NA coding for tT G2, IFNγ, TLR2 and My D88, and the quantity was expressed as fold change compared to controls. Control group was represented by duodenal normal specimens from 15 healthy subjects undergoing endoscopy for functional symptoms. Comparisons among continuous variables were performed by One way analysis of variance(ANOVA) and Bonferroni’s test. The χ~2 test was used for categorical variables. Pearson’s test was used to evaluate correlations. Receiver operating curves were drawn for all four markers to estimate sensitivity and specificity in discriminating the development of CD and GS.RESULTS After a period of follow up of 21.7 ± 11.7 mo, the following diagnoses were achieved: gluten related disorders in 48 subjects(31 CD; 17 GS) and non-gluten related ones in 41(29 Irritable Bowel Syndrome- IBS; 12 Others). CD patients had the highest tT G2 levels(8.3 ± 4.5). The ANOVA plus Bonferroni analysis showed that CD > Other ME > GS = IBS > negative controls. A cut off value of 2.258 was able to discriminate between CD and GS with a sensitivity of 52.94% and a specificity of 87.1%. Additionally, CD patients had the highest IFNγ levels(8.5 ± 4.1). ANOVA plus Bonferroni demonstrated CD > Other ME > GS = IBS > negative controls. A cut off of 1.853 was able to differentiate CD and GS with a sensitivity of 47.06% and a specificity of 96.77%. Patients with non gluten-related causes of ME exhibited the highest TLR2 levels(6.1 ± 1.9) as follows: Other ME > CD = GS = IBS > negative controls. TLR2 was unable to discriminate CD from GS. Patients with CD overexpressed MyD 88 levels similarly to non gluten-related causes of DL(7.8 ± 4.9 and 6.7 ± 2.9), thus CD = Other ME > GS = IBS > negative controls. A cut off of 3.722 was able to differentiate CD from GS with a sensitivity of 52.94% and a specificity of 74.19%. IELs count(15-25 and more than 25/100 enterocytes) strongly correlated with mR NA levels of all tested molecules(P < 0.0001).CONCLUSION Our results confirm that a single marker is unable to predict a discrimination among ME underlying conditions as well as between CD and GS. Mucosal high levels of t TG and IFNγ m RNA may predict the development of CD more than GS with high specificity, despite an expected low sensitivity. TLR2 does not discriminate the development of CD from GS. My D88 levels indicate that intestinal permeability is more increased when a severe intestinal damage underlies ME in both gluten related and unrelated conditions. Therefore, the results of the present paper do not seem to show a clear translational value.

Microbial transglutaminase should be considered as an environmental inducer of celiac disease

Due to the recent interest in food additives that can act as triggering factors in autoimmune diseases including celiac disease(CD),the present letter to the editor expands on the microbial transglutaminase(mTG).It is heavily consumed by a plethora of food processing industries as“glue of proteins”thus improving product’s stability,texture and shelf life.However,more and more information is accumulated lately,questioning its safety.Its cross-linked gliadin complexes are immunogenic in CD.The enzyme increases gliadin uptake,is transported in a trans-epithelial way and deposited below the enterocyte’s line,has antiphagocytic activity,enhances intestinal permeability and creates luminal resistant isopeptide bonds.No doubt that mTG is beneficial to food industries but a caveat to public health is highly recommended.

Erythrocytic transglutaminase inhibition hemolysis at presentation of celiac disease

Celiac disease (CD) is a common autoimmune condition.Previously it was considered to be a rare childhood disorder,but is actually considered a relatively common condition,present at any age,which may have multiple complications and manifestations.Hematological disorders of the disease are not uncommon.Among these disorders,the most frequently reported are anemias as a result of iron deficiency,often associated with folate and/or B12 deficiency.Anemias caused by hemolysis are very rarely reported in celiac patients.An 11-year-old girl with a previous uneventful medical history presented with severe hemolytic anemia.Hemolysis was Coombs negative,accompanied by inappropriate low reticulocyte count,despite exaggerated bone marrow hyperplasia of the erythroid precursors which showed normal maturation.Serology for recent infections,including EpsteinBarr virus,parvovirus B19,cytomegalovirus and mycoplasma,were all negative.Levels of serum IgA,IgG and IgM,were all within normal ranges for age.Screeningfor anti-DNA,antinuclear,antineutrophil cytoplasmic,antimicrosomal,antithyroglobulin,and antimitochondrial antibodies and lupus anticoagulants,was negative.She was also negative for human immunodeficiency virus.Conventional therapy with corticosteroids and intravenous immunoglobulin failed.CD was serendipitously discovered upon screening for anti-tissue transglutaminase autoantibodies.The disease was confirmed by biopsy of the small intestine mucosa.The patient recovered with gluten-free diet.A unique case of CD is presented.CD should be serologically screened in each patient with Coombs negative "immune"hemolytic anemia,particularly if accompanied by "reticulocytopenia".A new hemolytic mechanism and very speculative explanation for "reticulocytopenia"are discussed.

Inhibitory Effect of Tissue Transglutaminase (tTG) Antisense Oligodeoxynucleotides on tTG Expression in Cultured Bovine Trabecular Meshwork Cells

To study the effect of tTG fully phosphorothioated antisense oligodeoxynucleotides （tTG-ASDON） on tTG expression in cultured bovine trabecular meshwork cells （BTMCs） in vitro and explore a new treatment alternative for primary open angle glaucoma （POAG）, the ASDON1 and ASDON2 complementary to the protein codogram region of tTG were designed, synthesized and phosphorothioated according to the secondary structure of tTG. The ASDON1 and ASDON2 were embedded in Lipofectamine and transfected into BTMCs. The untreated group served as negative controls. The expression of tTG in the mRNA and protein level were measured by semi-quantitative RT-PCR and immunohistochemical technique-Supervision method respectively. Our results showed that both the mRNA and the protein of tTG with tTG-ASDON1 and tTCr-ASDON2 were significantly decreased as compared with that of the controls （P〈0.05）. On the other hand, no significant difference was found between the ASDON1 group and the ASDON2 group. It is concluded that the expression of tTG mRNA and protein in cultured BTMC are down-regulated by tTG- ASDON. As a result, tTG-ASDON may be used for the treatment of POAG through the inhibitory effect on the expression of tTG.

The Impact of Microbial Transglutaminase on the Quality and Antioxidant Activity of Camel-Milk Soft Cheese

This study aimed at investigating the impact of adding microbial transglutaminase (MTGase) after rennet addition on some properties of fresh soft cheese made from camel milk. MTGase was added to milk at concentration of 80, 100 and 120 U/L after 20 and 30 min of renneting. The chemical composition, yield, hardness, antioxidant activity and sensory properties of cheese were estimated. Enzymatic protein crosslinking was analyzed by SDS-PAGE. Results revealed that MTGase-treated cheeses were higher in moisture and lower in protein content compared to control. In addition, the concentration of MTGase and time of addition significantly (P 0.05) impacted these parameters. Among treated cheeses, samples with 80 U of MTGase and addition time of 20 min were the highest in total solids and protein content. Adding MTGase significantly (P 0.05) increased the cheese yield, however, increased MTGase concentration at any time of addition did not improve it. The electrophoretic patterns of MTGase-cheese proteins showed a reduction in the intensity of caseins bands and the appearance of new protein fractions with high molecular weights. However, the changes in the intensity of the whey proteins bands were not sufficiently clear as caseins. The cheese hardness was significantly (P 0.05) affected by adding MTGase. Cheese containing 80 U of MTGase had the highest hardness value compared to control and other treated samples. The antioxidant activity of cheese was negatively influenced by adding the enzyme. The use of MTGase enhanced the mouthfeel, texture and overall acceptability of cheese. However, the effect of MTGase concentration and addition time was not significant (P > 0.05) on the sensory attributes. In conclusion, adding MTGase to milk at concentration of 80 U after 20 min of renneting is recommended to improve the yield, textural and some sensory properties of fresh soft cheese made from camel milk.

Children with celiac disease and high tTGA are genetically and phenotypically different

AIM:To investigate whether celiac disease(CD)patients with tissue-transglutaminase antibody(tTGA)≥100 U/mL are different from patients with lower tTGA levels.METHODS:Biopsy-proven(MarshⅢ)pediatric CD patients(n=116)were prospectively included between March 2009 and October 2012.The biopsies were evaluated by a single pathologist who was blinded to all of the patients’clinical data.The patients were distributed into 2 groups according to their tTGA level,which was measured using enzyme-linked immunoassay:tTGA≥100 U/mL and Ttga<100 U/mL.The patients’characteristics,symptoms,human leukocyte antigen(HLA)genotype and degree of histological involvement were compared between the 2 groups.RESULTS:A total of 34(29.3%)children had tTGA values<100 U/mL and 82(70.7%)tTGA levels of≥100 U/mL.Patients with high tTGA levels had lower average body weight-for-height standard deviation scores(SDS)than did patients with tTGA<100 U/mL(-0.20±1.19 SDS vs 0.23±1.03 SDS,P=0.025).In the low tTGA group,gastrointestinal symptoms were more common(97.1%vs 75.6%,P=0.006).More specifically,abdominal pain(76.5%vs 51.2%;P=0.012)and nausea(17.6%vs 3.7%,P=0.018)were more frequent among patients with low tTGA.In contrast,patients with solely extraintestinal manifestations were only present in the high tTGA group(18.3%,P=0.005).These patients more commonly presented with aphthous stomatitis(15.9%vs 0.0%,P=0.010)and anemia(32.9%vs 11.8%,P=0.019).In addition,when evaluating the number of CD-associated HLA-DQ heterodimers(HLA-DQ2.5,HLA-DQ2.2 and HLA-DQ8),patients with low tTGA levels more commonly had only1 disease-associated heterodimer(61.8%vs 31.7%,P=0.005),while patients with high tTGA more commonly had multiple heterodimers.Finally,patients with tTGA≥100 U/mL more often had a MarshⅢc lesion(73.2%vs 20.6%,P≤0.001)while in patients with low tTGA patchy lesions were more common(42.4%vs6.8%,P≤0.001).CONCLUSION:Patients with tTGA≥100 U/mL show several signs of more advanced disease.They also carry a larger number of CD associated HLA-DQ heterodimers.

转谷氨酰胺酶4在前列腺癌进展及预后中的作用

Transglutaminase 4 has been shown to enhance various biological properties of prostate cancer cells, e.g., cell-matrix adhesion, invasiveness and the epithelial-mesenchymal transition. The objectives of this study were to investigate the associations between transglutaminase 4 expression and the established features and biochemical recurrence of prostate cancer. Transglutaminase 4 immunostaining was performed on a tissue microarray. The expression of transglutaminase 4 was evaluated by a scoring method based on the intensity and extent of staining. The clinical and pathological information was obtained through a review of medical records. Follow-up data were obtained by consulting the hospital medical records and the prostate cancer database of our department and by contacting patients or family members. We then compared the transglutaminase 4 expression levels between the prostate cancer tissues and the paracarcinoma tissues and evaluated the correlation of transglutaminase 4 expression with the clinical parameters and biochemical recurrence of prostate cancer. Our results indicated that the transglutaminase 4 staining was significantly higher in tumour tissue than in paracarcinoma tissue （P^O.O01） and was positively associated with higher Gleason score （P^O.O01） and higher prostate-specific antigen level （P=0.005）. Patients with transglutaminase 4 overexpression experienced shorter biochemical recurrence-free survival after surgery （P=0.042） in the univariate analysis but not in the multivariate analysis （P=0. 139）, which indicated that transglutaminase 4 may serve as a potential predictor of biochemical recurrence of prostate cancer.