With the aim of developing a new enzyme-linked immunosorbent assay test to detect autoantibodies in the sera of rheumatoid arthritis patients with a high sensitivity and specificity using synthetic ...citrullinated peptides of fibrin (which is abundant in rheumatoid synovium) as antigenic substract, peptides belonging to alpha - and beta -fibrin chains were selected by computer-aided prediction of antigenicity and epitope mapping and synthesized in solid phase. We analysed by enzyme-linked immunosorbent assay 133 sera from patients with well-characterized rheumatic diseases, including 67 patients with rheumatoid arthritis. The results of the immunoassays reported highlight the usefulness of fibrin-related peptides in rheumatoid arthritis diagnosis and, especially, the ability and specificity of the Cit super(621,627,630) alpha -fibrin(617-631) ( alpha fib617) peptide sequence to recognize the autoantibodies that are present in rheumatoid arthritis patients.
In renal transplantation, chronic allograft nephropathy is the leading cause of long-term graft losses, transplant glomerulopathy being its glomerular form. Differential diagnosis from recurrent or ...de novo membranoproliferative glomerulonephritis should be established. Whether hepatitis C virus is associated with cryoglobulinemia and glomerular damage in renal allograft recipients, as in native kidneys, is not known. We identified six hepatitis C virus-infected renal allograft recipients with proteinuria higher than 1.5 g/day, microhematuria, and membranoproliferative glomerulonephritis. Virologic and immunologic studies were conducted. Low serum levels of circulating immune complexes and cryoglobulins were observed, which were type II immunoglobulin G polyclonal-immunoglobulin Mk monoclonal in all six patients. Classical serum complement pathway activation and at least one type of autoantibodies were present in all of them. Hepatitis C virus RNA was found in higher concentrations in cryoprecipitate than in serum (percentage of enrichment ranged from 341 to 18,200%). Hepatitis C virus genotype was 1b in 4 of 6 patients, 1a in 1 of 6 patients, and 2a in 1 of 6 patients. In renal histology prominent parietal diffuse deposition of immunoglobulin M was the rule. Glomerular subendothelial electron-dense deposits with fibrillar appearance were observed in the two patients in which electron microscopy provided information about glomeruli. In renal allograft recipients hepatitis C virus infection may be associated with type II cryoglobulinemia which may lead to membranoproliferative glomerulonephritis. Immunologic and virologic studies may help to differentiate hepatitis C virus-associated membranoproliferative glomerulonephritis from transplant glomerulopathy.
The prevalence of hepatitis C virus antibody and its relationship to the severity of liver disease in chronic alcoholic patients has been assessed, using a recently developed enzyme immunoassay and ...confirmed by a recombinant immunoblot assay, in 144 patients (mean age +/- S.D. = 44.4 +/- 11.3 yr) who had consumed greater than 80 gm/day ethanol for greater than 5 yr. Hepatic disease was evaluated by clinical and biochemical studies and by liver biopsy when appropriate. In addition, 76 liver biopsy specimens from these patients were analyzed to determine whether liver lesions were similar in alcoholic patients with and without hepatitis C virus antibodies. According to clinical and histological features alcoholic patients were divided into five groups: normal liver (45 patients), fibrosteatosis (20 patients), alcoholic hepatitis (14 patients), cirrhosis (61 patients) and chronic hepatitis (4 patients). Hepatitis C virus antibodies were present in 35 alcoholic patients (24.3%). The prevalence of hepatitis C virus antibodies correlated with the severity of liver injury: 2.2% in patients without liver disease, 20% in those with fibrosteatosis, 41.4% in those with alcoholic hepatitis and 42.6% in those with cirrhosis. Hepatitis C virus antibodies were found in one of the four patients with chronic hepatitis (p less than 0.001). Furthermore, patients positive for hepatitis C virus antibodies with normal liver or fibrosteatosis showed higher serum bilirubin and gamma-globulin concentrations and lower aminopyrine breath test scores than did patients negative for hepatitis C virus antibodies with normal liver or fibrosteatosis. Similar differences between patients with and without hepatitis C virus antibodies were observed in patients with alcoholic hepatitis or cirrhosis.
Transplantation of kidneys from donors with hepatitis C antibody into recipients pre-transplantation anti-HCV. Hepatitis C virus (HCV) is transmitted by organ transplantation. Consequently, several ...organ procurement organizations have imposed a moratorium on use of organs from anti-HCV positive donors. Because of the inadequate supply of cadaver kidneys for transplantation, we adopted a policy to transplant kidneys from anti-HCV donors into anti-HCV positive recipients. During the period between March 1990 and December 1992, 24 anti-HCV positive dialysis patients received a kidney from anti-HCV positive donors (group I) and 40 anti-HCV positive patients received a kidney from anti-HCV negative donors (group II). We compared the prevalence of liver disease, anti-HCV, HCV RNA, graft and patient survival between groups.Pre-transplantation 17 of 24 (71%) patients in group I and 31 of 40 (79%) of patients in group II had serum HCV RNA. Post-transplantation follow-up was 26 ± 8 months and 30 ± 10 months in groups I and II, respectively. During follow-up, elevated ALT levels were present in 7 of 24 (29%) and 16 of 40 (40%) of patients in groups I and II, respectively (P > 0.05). Post-transplantation, all patients in both groups retained anti-HCV. The prevalence of HCV RNA post-transplantation was 22 of 23 (96%) patients in group I and 30 of 39 (77%) of patients in group II (P > 0.05). Graft and patient survival in group I (96% and 100%, respectively) were not significantly different from those in group II (93% and 98%, respectively). The results of this study demonstrate the short-term safety of using kidneys from anti-HCV positive donors in anti-HCV positive recipients. However, this policy may not prevent transmission of HCV. A safer strategy would be to transplant kidneys from anti-HCV positive donors into recipients with HCV RNA.
Mspl polymorphism of the human p53 gene de la Calle-Martin, Oscar; Romero, Matilde; Fabregat, Virginia ...
Nucleic acids research,
08/1990, Letnik:
18, Številka:
16
Journal Article
From 1981 to 1987, 26 outbreaks of asthma caused by the inhalation of soybean dust, affecting a total of 688 individuals, were detected in Barcelona, Spain. Because only a small proportion of ...asthmatic individuals living in Barcelona expressed the epidemic phenotype, it is hypothesized that a genetically determined human leukocyte antigen (HLA) Class II factor could have played a role in the susceptible individuals. Accordingly, we studied the distribution of both HLA-DR and HLA-DQ in soybean epidemic asthmatic patients. An analysis of the HLA-DR and HLA-DQ genes for genetic polymorphisms of the beta 1 chain was done with the polymerase chain reaction (PCR) in 78 soybean epidemic asthma patients, and the findings were compared with those for 67 nonepidemic asthmatic individuals and 168 individuals from the general population. An allelic disequilibrium could be established; the risk of epidemic asthma was particularly associated with the DRB1*13 gene (p value corrected for multiple comparisons < 0.02). The association observed for the DRB1*13 gene was stronger in individuals in the lowest tertile for total IgE, with an estimated risk with a 95% confidence interval (CI), of 14.5 (1.6 to 130.8). The combination of two genes from among the DRB1*05-05, DRB1*05-06, and DRB1*06-06 genes was present in epidemic asthmatic subjects only. No association with an HLA-DQB1 allele could be observed. Genetic predisposition could contribute to the response of some asthmatic patients to exposure to soybean dust, having led to their being affected during the epidemics of asthma in Barcelona.
Around 50% of new cases of type 1 diabetes mellitus (DM1) are seen in subjects aged above 15 years. It is of particular interest the characterization of such a population.
a) to characterize a group ...of non-pediatric subjects with DM1 at the onset of the disease; b) to evaluate the prognosis of the disease under conventional intensive insulin therapy, and c) to investigate the presence of mutations in the HNF-1* gene in those subjects who did not display pancreatic autoimmune markers.
All subjects with an age >= 15 and 35 years recently diagnosed DM1 (1998-2001) were included in the study. Pancreatic cell function was assessed by glucagon test (at onset and at 12 months). The presence of pancreatic autoantibodies, GAD, IA2 and IAA was evaluated. HLA class II genes and the 10 exons of HNF-1* gene were analyzed from genomic DNA.
We studied 86 subjects (32 women, 23.9 5.3 year-old). Eighty percent of subjects were positive for any of the studied autoantibodies. Alone or in combination, GAD was positive in 68.6% of subjects, IA2 in 45.3% and IAA in 27.9% of them. Most frequent haplotype was DRB1*0301-DQA1*0501-DQB*0201. There were no differences with regard to clinical, metabolic or genetic characteristics among those subjects with or without presence of pancreatic autoantibodies (at onset and at 12 months). We did not find mutations in the HNF-1* gene in any of the subjects included in our study. After 12 months of follow-up, cell function remained unaltered in comparison with that observed at the onset of the disease.
Clinical, immunological and HLA characteristics of a non-pediatric DM1 population are in agreement with expected results. The absence of pancreatic autoimmune markers neither rules out the existence of type 1A diabetes mellitus nor is associated with mutations in the MODY-3 gene. A therapeutic programme using conventional intensified insulin treatment prevents the impairment of insulin secretory capacity for a short-term follow-up.
1. The power of the aerobic metabolic pathway correlates well with successful physical performance in endurance sports events. The ability to alter the pathway through training presents well-known ...limitations, and consequently a good genetic endowment is essential to participate in elite sporting activities. 2. In 32 subjects (16 healthy pairs of male twin sportsmen, 8 monozygotic and 8 dizygotic) zygosity was determined by means of the genetic analysis of human leucocyte antigen (HLA) system specificities at class I and II loci and other genetic variants. The subjects performed a progressive exercise test on a treadmill to ascertain the maximal oxygen uptake (VO2max), measured by an automatic breath-by-breath analyser. We have considered the relationship between the A, B and C loci of the HLA system and VO2max. 3. We found a high correlation between the presence of both HLA A2 and A11 and VO2max. In the A2A11 group (n = 6) we found a VO2max (mean +/- SD) equal to 71 +/- 4 ml min-1 kg-1. The group without this pair of alleles (n = 26) showed a much lower aerobic power (58 +/- 5 ml min-1 kg-1). Differences between the two groups were found to be largely significant (P < 0.001). It is noteworthy that in two pairs of dizygotic twins, the higher VO2max value corresponded to the twin with the A2A11 allele. 4. The very marked concordance between the presence of the A2A11 locus of the HLA system and the VO2max could be of great interest for the identification of outstanding performers.
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