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Biomedical subjects

Luis Rodrigo

Publications and source records attributed to Luis Rodrigo.

31 records · Page 2Linked to original sources
PubMed2004

Serum immunological profile in patients with chronic autoimmune cholestasis.

AIM: To compare patients who had biochemical and histological features of chronic autoimmune cholestasis (CAIC) using serological autoantibody profiling. METHODS: Patients (n = 174 CAIC; 79 AMA(-) and 95 AMA(+)) were profiled for the following antibodies: antinuclear antibodies (ANAs), antimitochondrial antibodies (AMAs), antismooth muscle actin (SMA, mainly F-actin), antiperinuclear cytoplasmic neutrophil antibodies (pANCAs), anti-SP100, anti-GP210, anti-M2 (2-oxo-acid dehydrogenase complexes), and antisoluble liver antigen (SLA). Liver specimens were reviewed according to staging, biliary interface activity, lobular hepatitis, granulomas, cholestasis, and florid ductal lesion. RESULTS: In patients who were AMA(-) by indirect immunofluorescence (IIF), 34.6% were positive for anti-M2 by immunoblotting. In 49 definitively AMA(-) patients, 24 (48.9%) showed ANA-primary biliary cirrhosis (PBC)-related antibodies (rim-like, multiple nuclear dots, anti-SP100, or anti-GP210). There were no differences in immunological, biochemical, or histopathological features between IIF-AMA(+) patients and AMA(-) patients with anti-M2 or ANA-PBC-related antibodies. AIH-related autoantibodies were found in 13 patients (7.5%). Patients with AMAs or ANA-PBC-related antibodies had higher IgM levels, whereas patients with antibodies highly specific for AIH had higher AST, bilirubin, and IgG levels, and AIH scores, and higher grades of lobular hepatitis. Overall, three distinct categories of patients were observed: AMA(+) or AMA(-) patients with ANA-PBC-related antibodies; AMA(-) patients with non-PBC-related ANAs; and patients with AIH-related antibodies together with serum PBC markers. CONCLUSION: Since these three groups had immunological, biochemical, and histopathological differences, they ought to be considered as separate clinical subentities rather than as merely AMA(-) or AMA(+) patients with autoimmune cholestasis.

Autoantibodies↗
PubMed2003

MICB typing by PCR amplification with sequence specific primers.

MICB is a member of the MIC (MHC class I chain-related gene) family. Sixteen MICB alleles have been described; however, the functional relevance and population distribution of MICB alleles or their potential association to disease has not yet been evaluated. In this study, we have developed a PCR system using sequence-specific primers (PCR-SSP) that allows unambiguous amplification of all MICB alleles. This approach has been applied to type 100 healthy unrelated individuals from the Spanish population. The extent of polymorphism in this population is lower than that initially expected, and only nine alleles were detected. The alleles MICB01021 (46%), MICB0103101 (13.5%), MICB0104 (13.5%) and MICB0106 (12.5%) were found to be the most frequent alleles. HLA-B and MICA transmembrane polymorphism typing were also performed in this population. Our data showed that MICB is in linkage disequilibrium with MICA and even with HLA-B. Thus, the linkage disequilibrium with MICA and HLA-B suggests that MICB is a potential candidate for those diseases classically associated with HLA class I alleles.

Alleles↗
PubMed2003

MHC class I chain-related gene A transmembrane polymorphism modulates the extension of ulcerative colitis.

Recent evidence from several studies has suggested a genetic predisposition in the pathogenesis of ulcerative colitis (UC), which is especially related with major histocompatibility complex (MHC) genes. The aim of this study was to investigate the possible association of human leukocyte antigen (HLA-B, HLA-DR) and MHC class I chain-related-transmembrane (MICA-TM) polymorphism with the behavior and extension of UC. We selected 121 unrelated patients with UC. These were divided into two groups according to the extension of the disease: 31 patients with distal UC and 90 with wide extension UC; 116 blood donors were also selected as healthy controls, all of whom were typed for HLA-B, HLA-DR, and MICA-TM alleles. HLA-B7 was found to be overrepresented in distal UC patients compared with those with extensive UC (p(c) = 0.007, OR = 5.33) and healthy controls (p(c) = 0.03, OR = 4.09). The MICA-A5.1 allele was also increased in distal UC (p(c) = 0.015, OR = 3.82) when compared with extensive forms. These alleles are in strong linkage disequilibrium in our population. The MICA-A5 allele was significantly increased in extensive forms when compared with healthy controls(p(c) = 0.02, OR = 2.4). According to our results, MICA-A5.1 allele seems to be protective against extensive forms of UC, and MICA-A5 may condition a worse progression of the disease. These results are in agreement with other studies that suggest a similar role of such alleles in other diseases, such as insulin-dependent diabetes mellitus and celiac disease.

Age of Onset↗
PubMed2003

Prospective analysis of risk factors for hepatocellular carcinoma in patients with liver cirrhosis.

Better knowledge of the risk factors associated with the appearance of hepatocellular carcinoma (HCC) could improve the efficacy of surveillance programs. A total of 463 patients aged 40 to 65 years with liver cirrhosis in Child-Pugh class A or B were included in a program of early diagnosis. The predictive value of different risk factors was evaluated using the Kaplan-Meier method and Cox regression model. Thirty-eight patients developed HCC. In the multivariate analysis, 4 variables showed an independent predictive value for the development of HCC: age 55 years or older, antibody to hepatitis C virus (anti-HCV) positivity, prothrombin activity 75% or less, and platelet count less than 75 x 10(3)/mm(3). According to the contribution of each of these factors to the final model, a score ranging between 0 and 4.71 points was constructed to allow the division of patients into 2 different risk groups. The low-risk group included those with a score of 2.33 points or less (n = 270; 4 with HCC; cumulative incidence of HCC at 4 years, 2.3%), and the high-risk group included those with a score greater than 2.33 (n = 193; 34 with HCC; cumulative incidence of HCC at 4 years, 30.1%) (P =.0001). In conclusion, a simple score made up of 4 clinical and biological variables allowed us to distinguish 2 groups of cirrhotic patients at high and low risk for the development of HCC. We believe this score can be useful in establishing a subset of cirrhotic patients in whom a surveillance program for early detection of HCC could be unjustified.

Adult↗
PubMed2003

Quality of life in patients with functional dyspepsia: a prospective 1-year follow-up study in Spanish patients.

BACKGROUND AND AIMS: The natural history of functional dyspepsia is not well known. We prospectively assess the quality of life and severity of symptoms in a group of Spanish patients with functional dyspepsia. PATIENTS AND METHODS: One hundred and twelve consecutive patients with functional dyspepsia, according to Rome II criteria, were prospectively followed up for 1 year. All patients completed symptom (Dyspepsia Questionnaire and the Gastrointestinal Symptoms Rating Scale) and quality of life [the Psychological General Well-Being (PGWB) Index and the General Health Questionnaire (GHQ)] questionnaires every 3 months. Only free antacid consumption was permitted during the study period. RESULTS: The group was made up of 81 women and 31 men with a mean age of 45 +/- 17 years; 66% of patients were infected with Helicobacter pylori, and ulcer-like dyspepsia (53%) was the predominant subgroup. At baseline, quality of life scores were low (PGWB, 87.1 +/- 17.6 and GHQ, 20.6 +/- 11.8), but these values gradually improved during the year of follow-up (PGWB, 107.7 +/- 1.1 and GHQ, 8.9 +/- 0.4). Digestive symptoms also decreased. In the multivariate analysis, the anxiety score on the PGWB index (Wald, 5.2; P = 0.02) and smoking status (Wald, 4.3; P = 0.04) were predictors of end quality of life. At baseline, patients with a high level of anxiety had a very reduced quality of life, although their symptom scores were similar to other patients. CONCLUSION: Quality of life is reduced in patients with functional dyspepsia. Some improvement in quality of life together with a decrease in the severity of symptom scores was seen during the 1 year of follow-up. We believe that both the reassurance of negative endoscopy and the scheduling of visits to the doctor favourably influence the quality of life.

Adult↗
PubMed2003

Characterization and clinical impact of antinuclear antibodies in primary biliary cirrhosis.

OBJECTIVES: The clinical impact of antinuclear antibodies in primary biliary cirrhosis is uncertain. We analyzed in detail the antinuclear antibodies reactivity of primary biliary cirrhosis patients and correlated the fine specificities observed with clinical, biochemical, and immunologic parameters. METHODS: A total of 96 consecutive primary biliary cirrhosis patients and 283 pathologic controls were studied. To dissect the fine antinuclear antibodies specificities we used different techniques, such as indirect immunofluorescence on cryostat tissue sections and cell culture (HEp-2 cells), counterimmunoelectrophoresis with thymus and spleen extracts, ELISA assays with recombinant Sp100 and purified gp210 and Lamin B receptor, and immunoblot with several recombinant nuclear and cytoplasmic antigens. RESULTS: Antinuclear antibodies were detected in 53% of patients, with the following hierarchy of specificities: 27% anti-Sp100, 16% "multiple nuclear dots," 16% anti-gp210, 16% anti-centromere, 7% XR1, 6% anti-lamin B receptor, 5% anti-SS-A/Ro, 5% anti-ribonucleoprotein, 4% XR2, 2% anti-SS-B/La, 2% perinuclear antineutrophil cytoplasmic antibodies, and 1% anti-double-stranded deoxyribonucleic acid. Several patients showed multiple specificities. The "multiple nuclear dots" pattern was detected more often in antimitochondrial antibodies negative patients. In particular, primary biliary cirrhosis specific antinuclear antibodies (anti-Sp100, anti-gp210, and anti-lamin B receptor) were detected in nine of 13 antimitochondrial negative primary biliary cirrhosis cases. Anti-gp210 was more frequent in patients with more pronounced cholestasis and more impaired liver function. CONCLUSIONS: Antinuclear antibodies reactivities are present in more than half of primary biliary cirrhosis patients and target diverse autoantigens located in distinct subnuclear structures. Anti-gp210 identifies a subgroup of primary biliary cirrhosis patients with more serious liver disease. Positivity for anti-Sp100, anti-gp210, and anti-lamin B receptor, either alone or in combination, may act as a serologic marker of antimitochondrial antibodies negative primary biliary cirrhosis.

Antibodies, Antinuclear↗
PubMed2003

TNF-alpha -308A promoter polymorphism is associated with enhanced TNF-alpha production and inflammatory activity in Crohn's patients with fistulizing disease.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) plays a key role in the inflammatory response and pathogenesis of Crohn's disease (CD). TNF-alpha -308A polymorphism within the TNF-alpha gene promoter has been associated with enhanced TNF-alpha production in vitro. The aim of this study was to investigate the effect of TNF-alpha promoter polymorphism at -308 on the susceptibility and phenotypic expression of fistulizing CD. METHODS: The distribution of -308 TNF-alpha genotypes was analyzed in 50 patients with fistulizing CD and 100 healthy matched controls. TNF-alpha, interleukin-1beta, and interleukin-6 serum levels were measured by ELISA. Serum amyloid-A, C-reactive protein, alpha1-antitrypsin, alpha1-acid glycoprotein, and haptoglobin were measured by nephelometry. RESULTS: No significant differences were found in the allele frequencies of the polymorphism between patients and controls. However, compared with -308GG patients, those carrying -308AG had a significant increase of serum levels of TNF-alpha (58 +/- 79 vs 8 +/- 19 pg/ml, p < 0.001), interleukin-1beta (36 +/- 45 vs 16 +/- 20 pg/ml, p = 0.048), and acute phase proteins (APPs). -308A carriers had also a higher frequency of arthritis (66% vs 26%, p = 0.039). The logistic regression model showed that the patients carrying -308A polymorphism had a relative risk for developing arthritis of 5.45 (95% CI = 1.1-25.6). No other clinical or analytical findings were predictive for the risk of development of arthritis. CONCLUSIONS: TNF-alpha -308A polymorphism is associated with enhanced TNF-alpha production, more intense inflammatory activity, and an increased risk for arthritis susceptibility in CD patients with fistulizing disease.

Acute-Phase Proteins↗
PubMed2002

MICA-A5.1 allele is associated with atypical forms of celiac disease in HLA-DQ2-negative patients.

We selected 38 consecutive celiac disease (CD) patients (from a group of 316 consecutive CD patients) and 91 healthy blood donors, all of whom were HLA-DQ2 (DQA1*0501/DQB1*0201) negative, and investigated the presence of the classically associated alleles HLA-DQ8 and HLA-DRB4. We also studied the distribution of MICA transmembrane alleles in the two clinical forms of the disease. For this reason, these 38 DQ2-negative patients were subdivided into two groups: 18 typical CD patients and 20 atypical CD patients. No differences were found in the distribution of the DRB4 allele between DQ2-negative patients and controls. The HLA-DQ8 heterodimer (DQA1*03xx/DQB1*0302) was increased in CD patients (29%) compared with controls (10%), but no statistical differences were found. No differences were observed in the frequency of these alleles between either group of CD DQ2-negative patients. MICA-A5.1 was increased in atypical CD patients when compared with the typical forms of disease ( P(c)=0.03) and with healthy controls (P(c)=0.002). No other MICA allele was found to be significantly increased in the groups under study. The presence of MICA-A5.1 in atypical CD DQ2-negative patients may indicate a possible role of this allele in the development of CD.

Adult↗
PubMed2002

High variability of HLA-B27 alleles in ankylosing spondylitis and related spondyloarthropathies in the population of northern Spain.

The distribution of B27 alleles (B*2701-23) was characterized by PCR-SSP in ankylosing spondylitis and related spondyloarthropathies (SpA) in a sample of B27 positive patients from northern Spain. Six B27 alleles were identified: B*2705,02,03,07,08 and B*2713. B*2705 and 02 were the most common alleles in the SpA studied: ankylosing spondylitis (AS) (n = 89), reactive arthritis (ReA) (n = 11), psoriatic arthritis (PsA) (n = 29), and inflammatory bowel disease (IBD) (n = 21). B*2707 and B*2708 were found in PsA patients and B*2703 in one patient with IBD. B*2713 was identified in a healthy control family. B*2713 has not been reported to be represented in either ethnic group. Thus, this population shows higher levels of B27 diversity than other Caucasian groups.

Alleles↗
PubMed2002

Autoantibodies to Golgi proteins in hepatocellular carcinoma: case report and literature review.

Anti-Golgi antibodies are a type of anticytoplasmic autoantibody rarely found during routine examination of pathological samples. Although they have been mostly associated with connective autoimmune diseases, they are also present in other clinical conditions, including few cases of liver dysfunction. In this report, we describe for the first time the presence of high titres of anti-Golgi antibodies in a patient with virus-C-induced hepatocellular carcinoma (HCC). By immunofluorescence, the patient's serum yielded a characteristic fluorescence pattern that corresponded to the presence of Golgi reactivity. On immunoblot, the serum disclosed three reactive bands of approximately 105, 79 and 59 kDa. In addition, we retrospectively analysed the presence of anti-Golgi antibodies in sera from 95 patients with chronic hepatitis C, in 32 patients with chronic hepatitis B, in 35 patients with HCC associated with either virus C (27 cases), virus B (five cases) or both virus C and virus B (three cases), and in 18 patients with HCC induced by alcoholism. We found an additional positive patient, beside the patient presented herein, with HCC induced by B virus infection, whereas all patients without HCC were negative. Thus, the overall frequency of anti-Golgi antibodies in our series of patients with virus-induced HCC was 5.5% (two cases out of 36). The mechanism involved in the appearance of anti-Golgi antibodies in HCC is discussed, along with a review of the reported cases of liver diseases associated with the appearance of Golgi autoantibodies.

Aged↗
PubMed2002

HFE gene mutations in alcoholic and virus-related cirrhotic patients with hepatocellular carcinoma.

OBJECTIVE: The increased risk of developing hepatocellular carcinoma in hereditary hemochromatosis has been associated with cirrhosis and hepatic iron overload. The aim of this study was to investigate the association between HFE gene mutations (C282Y, H63D) and hepatocellular carcinoma in patients with alcoholic and virus-related cirrhosis. METHODS: Serum markers of iron status and HFE mutations were determined in 179 patients with alcoholic cirrhosis and 98 patients with hepatitis B and/or hepatitis C virus-related cirrhosis. A total of 43 patients with alcoholic cirrhosis and 34 patients with virus-related cirrhosis had hepatocellular carcinoma. The control group consisted of 159 healthy bone marrow donors. RESULTS: No differences were found in the frequencies of mutations among patients with alcoholic cirrhosis, those with virus-related cirrhosis, and the control subjects. However, nine (20.9%) of the 43 patients with alcoholic cirrhosis and hepatocellular carcinoma were heterozygous for the C282Y mutation, compared with six (4.4%) of the 136 patients without tumor (p = 0.002). This difference was not found in patients with virus-related cirrhosis, with or without hepatocellular carcinoma, or the H63D mutation. The transferrin saturation was the only serum iron marker the value of which was significantly higher among C282Y heterozygotes with alcoholic cirrhosis compared to those without mutation. CONCLUSIONS: The high frequency of heterozygosity for the C282Y mutation in patients with alcoholic cirrhosis plus hepatocellular carcinoma suggests that the presence of this mutation could be associated with an increased risk of developing hepatocellular carcinoma in these patients.

Adult↗
PubMed2002

Celiac disease in autoimmune cholestatic liver disorders.

OBJECTIVES: In this study, serological screening for celiac disease (CD) was performed in patients with autoimmune cholestasis to define the prevalence of such an association and to evaluate the impact of gluten withdrawal on liver disease associated with gluten sensitive enteropathy. METHODS: Immunoglobulin A endomysial, human and guinea pig tissue transglutaminase antibodies, and immunoglobulin A and G gliadin antibodies were sought in 255 patients with primary biliary cirrhosis, autoimmune cholangitis, and primary sclerosing cholangitis. RESULTS: Immunoglobulin A endomysial and human tissue transglutaminase antibodies were positive in nine patients (seven primary biliary cirrhosis, one autoimmune cholangitis, and one primary sclerosing cholangitis), whose duodenal biopsy results showed villous atrophy consistent with CD. Two of these patients had a malabsorption syndrome, and one had iron-deficiency anemia. Clinical and biochemical signs of cholestasis did not improve after gluten withdrawal in the three patients with severe liver disease. A longer follow-up of the six celiac patients with mild liver damage is needed to clarify whether gluten restriction can contribute to slow down the progression of liver disease. CONCLUSIONS: The high prevalence of CD (3.5%) in autoimmune cholestasis suggests that serological screening for CD should be routinely performed in such patients by immunoglobulin A endomysial or human tissue transglutaminase antibodies.

Adult↗