Biomedical subjects

Giuseppe Montalto

Publications and source records attributed to Giuseppe Montalto.

At least 19 recordsLinked to original sources

PubMed2006

Food allergy in gastroenterologic diseases: Review of literature.

Food allergy is a common and increasing problem worldwide. The newly-found knowledge might provide novel experimental strategies, especially for laboratory diagnosis. Approximately 20% of the population alters their diet for a perceived adverse reaction to food, but the application of double-blind placebo-controlled oral food challenge, the "gold standard" for diagnosis of food allergy, shows that questionnaire-based studies overestimate the prevalence of food allergies. The clinical disorders determined by adverse reactions to food can be classified on the basis of immunologic or nonimmunologic mechanisms and the organ system or systems affected. Diagnosis of food allergy is based on clinical history, skin prick tests, and laboratory tests to detect serum-food specific IgE, elimination diets and challenges. The primary therapy for food allergy is to avoid the responsible food. Antihistamines might partially relieve oral allergy syndrome and IgE-mediated skin symptoms, but they do not block systemic reactions. Systemic corticosteroids are generally effective in treating chronic IgE-mediated disorders. Epinephrine is the mainstay of treatment for anaphylaxis. Experimental therapies for IgE-mediated food allergy have been evaluated, such as humanized IgG anti-IgE antibodies and allergen specific immunotherapy.

Anaphylaxis↗

PubMed2006

Cyclooxygenases in hepatocellular carcinoma.

Many epidemiological studies demonstrate that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) reduce the incidence and mortality of certain malignancies, especially gastrointestinal cancer. The cyclooxygenase (COX) enzymes are well-known targets of NSAIDs. However, conventional NSAIDs non-selectively inhibit both the constitutive form COX-1, and the inducible form COX-2. Recent evidence indicates that COX-2 is an important molecular target for anticancer therapies. Its expression is undetectable in most normal tissues, and is highly induced by pro-inflammatory cytokines, mitogens, tumor promoters and growth factors. It is now well-established that COX-2 is chronically overexpressed in many premalignant, malignant, and metastastic cancers, including hepatocellular carcinoma (HCC). Overexpression of COX-2 in patients with HCC is generally higher in well-differentiated HCCs compared with less-differentiated HCCs or histologically normal liver, suggesting that COX-2 may be involved in the early stages of hepatocarcinogenesis, and increased expression of COX-2 in noncancerous liver tissue has been significantly associated with shorter disease-free survival in patients with HCC. In tumors, overexpression of COX-2 leads to an increase in prostaglandin (PG) levels, which affect many mechanisms involved in carcinogenesis, such as angiogenesis, inhibition of apoptosis, stimulation of cell growth as well as the invasiveness and metastatic potential of tumor cells. The availability of novel agents that selectively inhibit COX-2 (COXIB), has contributed to shedding light on the role of this molecule. Experimental studies on animal models of liver cancer have shown that NSAIDs, including both selective and non-selective COX-2 inhibitors, exert chemopreventive as well as therapeutic effects. However, the key mechanism by which COX-2 inhibitors affect HCC cell growth is as yet not fully understood. Increasing evidence suggests the involvement of molecular targets other than COX-2 in the anti-proliferative effects of COX-2 selective inhibitors. Therefore, COX-inhibitors may use both COX-2-dependent and COX-2-independent mechanisms to mediate their antitumor properties, although their relative contributions toward the in vivo effects remain less clear. Here we review the features of COX enzymes, the role of the expression of COX isoforms in hepatocarcinogenesis and the mechanisms by which they may contribute to HCC growth, the pharmacological properties of COX-2 selective inhibitors, the antitumor effects of COX inhibitors, and the rationale and feasibility of COX-2 inhibitors for the treatment of HCC.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2006

Interleukin-6 and its soluble receptor in patients with liver cirrhosis and hepatocellular carcinoma.

AIM: To evaluate the immunohistochemical localization of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) on tumor tissue specimens from patients with hepatocellular carcinoma (HCC) and the serum levels of IL-6 and sIL-6R in a group of patients with HCC as well as liver cirrhosis (LC) in a group of patients with LC alone and in a control group. METHODS: Three groups of subjects were studied: group I (n = 83) suffering from HCC and LC, group II (n = 72) suffering from LC alone and group III (n = 42) as healthy controls. All patients had hepatitis C virus infection. Serum IL-6 and IL-6R levels were determined using a commercially available ELISA kit. Immunohistochemistry was performed using the streptavidin-biotin complex and rabbit polyclonal antibodies against IL-6 and IL-6R. RESULTS: Immunohistochemistry analysis showed a medium to strong cytoplasmic and membrane reactivity for IL-6 and IL-6R respectively, in at least 40% of cases of HCC, whereas liver cirrhosis patients and controls were negative for IL-6 or showed a very mild and focal dot-like cytoplasmic reaction for IL-6R. Serum IL-6 levels in HCC group were significantly higher than those in LC and control groups (P < 0.0001). There was no significant difference in sIL-6R concentrations among 3 groups. When the patients with HCC were divided into groups according to Okuda's classification, a significant serum increase of IL-6 and sIL-6R level was observed from stage I to stage III (P < 0.02, P < 0.0005). When HCC and LC patients were divided into 3 classes of cirrhosis severity according to Child-Pugh, values in HCC patients were significantly higher than those in LC patients for each corresponding class (P < 0.01). CONCLUSION: IL-6 serum levels in HCC patients are higher than those in LC patients and controls, suggesting an increased production of this cytokine by neoplastic cells. sIL-6R values are similar in all groups, increasing only in stage III HCC patients. These data suggest that they have a closer relationship with the neoplastic mass rather than with the residual functioning hepatic mass.

Adult↗

PubMed2006

Unexplained elevated serum pancreatic enzymes: a reason to suspect celiac disease.

BACKGROUND & AIMS: The frequency of elevated serum pancreatic enzymes in patients with celiac disease (CD) is unknown. The aim of this study was to evaluate the serum levels of pancreatic enzymes in CD patients. METHODS: Serum pancreatic isoamylase and lipase levels were assayed in 90 adult and 112 pediatric consecutive CD patients at diagnosis and after 12 months of gluten-free diet (GFD). Serum elastase and trypsin levels were assayed in a subgroup of adult CD patients. Pancreatic ultrasonography was also performed. RESULTS: Twenty-six adult (29%) and 29 pediatric (26%) CD patients exhibited elevated values of serum pancreatic amylase and/or lipase; trypsin was elevated in 69% and elastase in 19%. The frequency of elevated serum pancreatic enzymes observed was identical in the patients with "typical" and "atypical" CD symptoms and in the asymptomatic patients. Most of the elevated values were lower than 2-fold the threshold limits. Elevated pancreatic enzymes were not associated with alcohol consumption, drug use, presence of abdominal pain, or diabetes mellitus. Abdominal ultrasound scan showed no abnormal findings in the pancreatic region in any of the CD patients. After 12 months of GFD, pancreatic amylase was elevated in 3 cases and lipase in 2 cases; these patients had not strictly adhered to the GFD. CONCLUSIONS: We demonstrated a frequency of about 25% of elevated pancreatic enzymes values in CD patients, including subjects without gastrointestinal manifestations and apparently asymptomatic subjects. The finding of elevated serum amylase or lipase level, in the absence of signs of pancreatic disease, would appear to suggest a need to screen for celiac disease.

Adolescent↗

PubMed2006

Thyroid sarcoidosis as a unique localization.

Sarcoidosis is a systemic disorder characterized by granulomatous lesions, principally affecting the lungs. There are numerous reports in the literature of an associated involvement of the thyroid, much more frequently in hypothyroid than in hyperthyroid subjects. The present case report refers to a woman presenting with thyroid nodules and normal biochemical levels and thyroid function parameters, while histology revealed sarcoid-type lesions. Subsequent investigations and a long follow-up showed no evidence of involvement of other sites, including the lungs. Consequently, after a long period of normal health associated with the negative results of the examinations, a diagnosis of sarcoidosis limited to the thyroid was proposed, which was cured by thyroidectomy.

Adult↗

PubMed2006

The selective cyclooxygenase-1 inhibitor SC-560 suppresses cell proliferation and induces apoptosis in human hepatocellular carcinoma cells.

Two isoforms of cyclooxygenase (COX) are known, and to date most studies have implicated COX-2 in the development and progression of various human cancers. Increasing evidence suggests that COX-1 may also play a similar role. Indeed, we have recently observed that the dual COX-1/COX-2 inhibitor indomethacin induces apoptosis in human hepatocellular carcinoma (HCC) cell lines more effectively than the selective COX-2 inhibitors, possibly implicating COX-1 in HCC. In this study we investigated the expression of COX-1 in non-tumor and malignant human liver tissues, as well as the effects of the highly selective COX-1 inhibitor SC-560 on cell growth and apoptosis in human HCC cell lines. Expression of COX-1 was detected in nearly all the samples assayed, although with a high variability between non-tumoral (NT) and malignant tissues. The percentage of COX-1 positive cells was significantly higher in the NT tissues than in the tumors (p<0.0001). In well-differentiated HCC COX-1 expression was significantly higher than in the poorly-differentiated tissues (p<0.05). SC-560 showed a dose- and time-dependent inhibitory effect on HCC cell growth. The combination of the COX-1 inhibitor with nimesulide and CAY10404, two selective COX-2 inhibitors, resulted in additive effects on cell growth inhibition. SC-560 also inhibited colony formation in soft agar and induced apoptosis in HCC cells in a dose-dependent manner. Moreover, SC-560 decreased the levels of the anti-apoptotic proteins survivin and XIAP and activated caspase-3 and -7 in a dose- and time-dependent fashion. In conclusion, we report for the first time that the selective COX-1 inhibitor SC-560 exhibits anti-tumor and apoptotic effects in human HCC cells. Overall, our previous and present results suggest that both COX-1 and COX-2 inhibitors may have potential therapeutic implications in HCC patients.

Aged↗

PubMed2005

Correlation between expression of cyclooxygenase-2 and the presence of inflammatory cells in human primary hepatocellular carcinoma: possible role in tumor promotion and angiogenesis.

AIM: To investigate the association of cyclooxygenase-2 (COX-2) expression with angiogenesis and the number and type of inflammatory cells (macrophages/Kupffer cells; mast cells) within primary hepatocellular carcinoma (HCC) tissues and adjacent non-tumorous (NT) tissues. METHODS: Immunohistochemistry for COX-2, CD34, CD68 and mast cell tryptase (MC(T)) was performed on 14 well-characterized series of liver-cirrhosis-associated HCC patients. COX-2 expression and the number of inflammatory cells in tumor lesions and surrounding liver tissues of each specimen were compared. Moreover, COX-2, CD34 staining and the number of inflammatory cells in areas with different histological degrees within each tumor sample were comparatively analyzed. RESULTS: The percentage of COX-2 positive cells was significantly higher in NT tissues than in tumors. COX-2 expression was higher in well-differentiated HCC than in poorly-differentiated tissues. Few mast cells were observed within the tumor mass, whereas a higher number was observed in the surrounding tissue, especially in peri-portal spaces of NT tissues. Abundant macrophages/Kupffer cells were observed in NT tissues, whereas the number of cells was significantly lower in the tumor mass. However, a higher cell number was observed in the well-differentiated tumor and progressively decreased in relation to the differentiation grade. Within the tumor, a positive correlation was found between COX-2 expression and the number of macrophages/Kupffer cells and mast cells. Moreover, there was a positive correlation between CD34 and COX-2 expression in tumor tissues. Comparison between well- and poorly-differentiated HCC showed that the number of CD34-positive cells decreased with dedifferentiation. However, COX-2 was the only independent variable showing a positive correlation with CD34 in a multivariate analysis. CONCLUSION: The presence of inflammatory cells and COX-2 expression in liver tumor suggests a possible relationship with tumor angiogenesis. COX-2 expressing cells and the number of macrophages/Kupffer cells and mast cells decrease with progression of the disease.

Aged↗

PubMed2005

Treatment of hepatocellular carcinoma in compensated cirrhosis with radio-frequency thermal ablation (RFTA): a prospective study.

BACKGROUND/AIMS: To assess the effectiveness and the safety of radio-frequency thermal ablation (RFTA) in patients with hepatocellular carcinoma (HCC) < or = 5 cm in compensated cirrhosis. METHODS: A cohort of 202 consecutive patients (165 Child-Pugh class A and 37 class B) was prospectively assessed. A single lesion was observed in 160/202 (79.2%), two lesions in 29/202 (14.3%), and three lesions in 13/202 (6.4%) of patients. RESULTS: Sixty-seven patients died. Survival rates were 80% at 12 months, 67% at 24 months and 57% at 30 months (Child-Pugh A 59% and Child-Pugh B 48%). By Cox regression analysis, survival was independently predicted by serum albumin levels > or = 35 g/L, platelet count > or = 100.000/mmc, tumor size < or = 3 cm, complete response at 1 month and Barcelona Clinic Liver Cancer (BCLC) staging classification. Overall recurrence rates were 22, 38, and 44% at 12, 24, and 30 months, respectively. One procedure-related death occurred. The proportion of major complications after treatment was 3.9%. CONCLUSIONS: A complete response after RFTA significantly increases survival. The longest survival is obtained in the presence of HCC < or = 3 cm and of higher baseline albumin levels and platelet counts. BCLC staging classification is able to discriminate patients with good or poor prognosis.

Aged↗

PubMed2004

Perihepatic lymph nodes and antiviral response in chronic HCV-associated hepatitis.

To identify predictive factors of response to interferon alpha (IFN-alpha) plus ribavirin therapy in patients with chronic hepatitis C (CHC), the presence of lymphadenopathy (LyA) of the hepatoduodenal ligament and other variables were investigated. A total of 110 patients with histologically proven CHC were enrolled in this study. Ultrasound (US) was performed at the start and end of therapy and 6 months after stopping therapy. At baseline, LyA was present in 35 (43.7%) of 80 patients with alanine aminotransferase (ALT) values and grading was significantly higher than in the LyA-negative group. LyA was more frequent in nonresponders (nonR) than in relapsers (relR) or sustained responders (susR). Lymph node volume (LyV) was significantly lower in susR than in nonR or relR (p < 0.05). Under antiviral treatment, the reduction in LyV was significantly higher in nonR (p < 0.01); in susR and relR, it was not significantly reduced. LyA totally disappeared in two patients of the susR group. Logistic regression analysis confirmed only a positive association of susR with grading and a negative association with staging (p < 0.02 and p < 0.006). In conclusion, this study suggests that US evidence of LyA is useful in evaluating the severity of a given chronic hepatitis C, but it cannot be proposed as a predictive index of response to antiviral treatment.

Adult↗

PubMed2004

Long-lasting remission of primary hepatic lymphoma and hepatitis C virus infection achieved by the alpha-interferon treatment.

Primary hepatic lymphoma is a rare but well-defined lymphoma entity that often pursues an aggressive clinical course. Most cases have been described in hepatitis C virus (HCV)-related chronic liver disease patients. Although anthracycline-based chemotherapy has been reported to be highly effective, the best therapeutic strategy has not been defined yet. The prognosis is dismal especially in patients treated with chemotherapy alone or when an advanced liver disease is present. Herein, we describe a case of primary hepatic large B-cell non-Hodgkin's lymphoma, in a patient with HCV chronic infection. After a minor response with eight cycles of CHOP chemotherapy, a complete and sustained remission was obtained with alpha-interferon at the daily dose of 3 MU. HCV-RNA clearance pace from the blood almost paralleled the response of the lymphoma and both diseases went in remission within 1 year of therapy. The possible place of alpha-Interferon in the treatment of primary hepatic lymphoma is discussed.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Expression of IAPs and alternative splice variants in hepatocellular carcinoma tissues and cells.

IAPs (inhibitors of apoptosis proteins) might have a major role in the apoptotic resistance that marks many cancers. The studies on IAPs in human HCC have focused on survivin or XIAP, indicating that their new or increased expression in this tumor is associated with a more unfavorable prognosis. The present results corroborate these findings, emphasizing the role that the coordinated expression of different IAPs and alternative splice variants might play in the adverse biology of hepatocellular carcinoma.

Alternative Splicing↗

PubMed2004

Expression of WISPs and of their novel alternative variants in human hepatocellular carcinoma cells.

WISPs (Wnt-induced secreted proteins) are members of the CCN (CTGF/Cyr61/Nov) family involved in fibrotic disorders and tumorigenesis. They have a typical structure composed of four conserved cysteine-rich modular domains, but variants of CCN members lacking one or more modules, generated by alternative splicing or gene mutations, have been described in various pathological conditions. WISP genes were first described as downstream targets of the Wnt signaling pathway, which is frequently altered in human hepatocellular carcinoma (HCC). In the present study, WISP mRNA expression was analyzed by RT-PCR in four human HCC cell lines (HepG2, HuH-6, HuH-7, HA22T/VGH). Our results show for the first time that WISP1, WISP1v, and WISP3 are expressed in HCC cell lines. Moreover, we identified two novel variants, generated by alternative splicing of WISP1 and WISP3, respectively, named WISP1 delta ex3-4 and WISP3vL. Overall, our study suggests that WISP transcripts may have a role in the development of HCC, although further studies are necessary to clarify the relative importance of the expression of wild-type WISPs, as well as of their novel variants, in this tumor type.

Alternative Splicing↗

PubMed2004

Induction of apoptosis and inhibition of cell growth in human hepatocellular carcinoma cells by COX-2 inhibitors.

The aim of the present study was to examine the effects of nonselective (indomethacin) and selective cyclooxygenase-2 (COX-2) inhibitors (NS-398, nimesulide, and CAY10404) on cell growth, cell cycle distribution, and apoptosis in three human hepatocellular carcinoma cell lines (HepG2, HuH-6, and HA22T/VGH) with different characteristics of differentiation and biological behavior. The four COX inhibitors showed a dose-dependent growth-inhibitory effect in all the cell lines. No substantial arrests in the progression of the cells through the cell cycle were observed after treatment of HuH-6 or HA22T/VGH for 48 h with the various inhibitors. On the other hand, there were significant increases in apoptosis, with the highest effect of cell kill being seen after treatment with indomethacin, especially in HuH-6. Our findings support the suggestion that selective or, perhaps more efficiently, nonselective COX-2 inhibitors may have potential therapeutic effects in hepatocellular carcinoma. Further studies must be carried out to better determine the possible mechanisms of these effects.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

Induction of apoptosis by the proteasome inhibitor MG132 in human HCC cells: Possible correlation with specific caspase-dependent cleavage of beta-catenin and inhibition of beta-catenin-mediated transactivation.

Proteasome inhibitors, like MG132, can exert cell growth inhibitory and apoptotic effects in different tumor types. The apoptotic mechanism of these compounds involves the activation of the effector caspases. beta-catenin, also an oncogene, represents one of the substrates of these proteases, but the consequences of its cleavage are poorly understood. We investigated its function during apoptosis induced by MG132 in three hepatocellular carcinoma (HCC) cell lines, endowed (HepG2 and HuH-6) or not (HA22T/VGH) with activating mutations of beta-catenin. Induction of apoptosis was associated with cell growth inhibition, accumulation of the cells at the G(2)/M phases of the cell cycle, as well as with fragmentation of beta-catenin (but not of alpha- or gamma-catenin) in all the cell lines. The cleavage of beta-catenin was inhibited by the caspase inhibitors Z-VAD-fmk and Z-DEVD-fmk. Fragmented beta-catenin was found in the nuclei of the treated cells. Analyses through the reporter plasmid pTOPflash showed that MG132 significantly reduces Tcf transcriptional activity in the cells. This was associated with a decrease in the mRNA expression of survivin and c-myc, which are target genes of the APC/beta-catenin/Tcf signaling. Nevertheless, Z-VAD-fmk or Z-DEVD-fmk did not reverse the MG132 effects on Tcf transcriptional activity, suggesting that the compound may affect this activity also by other mechanisms. Overall, the present study supports the therapeutic potential of the proteasome inhibitors in HCC.

Amino Acid Chloromethyl Ketones↗

PubMed2003

Local estrogen formation by nontumoral, cirrhotic, and malignant human liver tissues and cells.

We have investigated the activity and expression of aromatase enzyme in nontumoral, cirrhotic, and malignant human liver tissues and cells using both chromatographic and reverse transcription (RT)-PCR analyses. After 24- and 72-h incubation of tissue minces or hepatic cell lines with either testosterone or androstenedione as androgen precursor, human hepatocellular carcinoma (HCC) tissues and HepG2 hepatoma cells showed elevated aromatase activity, with estrogen formation rates being 20 and >95%, respectively, as opposed to nontumoral hepatic tissues and nonmalignant Chang liver (CL) cells, where no aromatase activity could be detected. Cirrhotic samples exhibited intermediate enzyme activity. Notably, exposure of HepG2 cells to the aromatase inhibitor Letrozole resulted in a striking decrease of estrogen formation, which became virtually absent at a Letrozole dose of 0.4 nM. RT-PCR analysis revealed markedly lower aromatase mRNA in both CL cells and nontumoral liver tissues, as compared with HepG2 cells and HCC samples. Cirrhotic specimens displayed variable transcript levels, in turn comparable with those observed in nontumoral or HCC tissues. Exon-specific RT-PCR showed prominent expression of exon I.3A-containing message and exon I.4-containing message in CL and HepG2 cells, as in nontumoral and HCC tissues, respectively. The present evidence implies that locally elevated estrogen formation in malignant human liver tissues and cells may have a role in the development and/or maintenance of human HCC, eventually leading to develop alternative strategies for treatment of HCC patients using antiaromatase agents.

Androgens↗

PubMed2003

Screening for celiac disease in patients with chronic liver disease.

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Adolescent↗

PubMed2003

Autoimmune enteropathy and colitis in an adult patient.

The presence of circulating autoantibodies to gut enterocytes has been very rarely described in adults and is considered a possible cause of refractory sprue. Our aims was to describe the case of an adult patient with serum anti-enterocyte autoantibodies associated with a clinical picture characterized by involvement of both the small intestine and colon. A female, age 50, had suffered from diarrhea with mucus and blood, abdominal pain, thinness, anemia, and leukopenia since the age of 20. She also suffered from HCV infection and had mild chronic hepatitis. Family history was positive for autoimmunity. Symptoms were reported to worsen after eating gluten-containing foods, but anti-transglutaminase and anti-endomysial antibodies were negative. Intestinal histology showed mild, patch villous atrophy with a high intraepithelial lymphocyte count, but a normal number of intraepithelial lymphocytes carrying the gamma/delta+ receptor. HLA was: A11, A31 (19), B52 (5), DR 15 (2), DR 14 (6), DR 51, DR 52, DQ1. Colonoscopy did not show ulcerations or erosions and colon histology showed a moderate inflammatory infiltrate without minor crypt distortion or granuloma. RAST tests were positive for lactalbumin, lactoglobulin, casein, egg, and gliadin. After commencement of an oligoantigenic diet, stool frequency initially decreased, but the presence of mucus in the stools persisted, with episodes of bloody diarrhea. After one year of diet, nutritional parameters were low and anemia associated with a low leukocyte count persisted. Upper and lower gastrointestinal endoscopy and histology of the small intestine and colon were virtually unchanged. Consequently, natural autoantibodies and enterocyte autoantibodies were assayed. The patient was positive for IgG class enterocyte autoantibodies at a titer of 1:34. No other organ-specific or non-organ-specific autoantibodies were positive. Prednisolone treatment was started and the symptoms improved. After one year of this treatment plus elimination diet she was reevaluated. Bowel movement frequency was normal, body weight increased, and the asthenia had completely regressed. IgG anti-enterocyte autoantibodies were absent. Histology of the distal duodenum showed a normal villus/crypt ratio and IEL infiltration was reduced. Colon histology showed a reduction in inflammatory infiltrate in the lamina propria. In conclusion, we report a case of generalized gut disorder in an adult patient, affecting both the small intestine and the colon and characterized by the presence of circulating anti-enterocyte autoantibodies. Systematic testing for enterocyte autoantibodies should be performed not only in patients with refractory sprue, but also in subjects with upper and lower intestinal symptoms who have not been definitively diagnosed.

Adult↗

PubMed2003

Screening for celiac disease in non-Hodgkin's lymphoma patients: a serum anti-transglutaminase-based approach.

Several studies have shown the existence of an association between celiac disease (CD) and non-Hodgkin's lymphoma (NHL). Our aim was to evaluate the usefulness of the serum anti-tissue transglutaminase (anti-tTG) antibody assay in screening for CD in consecutive NHL patients. In all, 80 consecutive patients (median age 61 years) with a new diagnosis of NHL were included. To compare the frequency of CD and of positive results for the anti-tTG assay, we enrolled 500 blood donors. In all patients serum anti-tTG was determined with two different ELISA: one based on tTG from guinea pig (gp-tTG) and the other based on human recombinant t-TG (h-tTG) as the antigens. Serum anti-endomysial antibodies (EmA) were also assayed. Subjects with positive serum EmA and/or anti-tTG underwent intestinal biopsy for histology study, HLA-DQ phenotype determination, and serum anti-gliadin (AGA) assay. Eight of 80 (10%) NHL patients were positive for anti-tTG ELISA--two of these exclusively for anti-gp-tTG and six for anti-h-tTG (7.5%). None of the 80 NHL patients were positive for serum EmA. The frequency of anti-tTG positivity in the blood donor controls was 2/500 (0.4%), significantly lower than that observed in the NHL patients (P < 0.0001). Both these blood donors were found to have CD. Only in one anti-h-tTG-positive NHL patient was there intestinal mucosa atrophy, and follow-up confirmed a CD diagnosis (CD frequency in NHL patients is 1.2%; versus blood donors: P = 0.4). In all the other seven anti-tTG-positive NHL patients a normal intestinal architecture was found, although, inflammatory infiltration of the lamina propria was observed in four patients. No anti-tTG-positive NHL patients, including the subject diagnosed as having CD, had a family history of CD, and all had normal weight and no signs of malabsorption. Anti-tTG false positive results were associated with a higher frequency of serum autoantibody positivity and T-cell type NHL. In conclusion, NHL patients the anti-tTG assay often gives discordant data with the EmA assay, with a high frequency of anti-tTG false positive results for CD diagnosis.

Adolescent↗