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Biomedical subjects

P J Venables

Publications and source records attributed to P J Venables.

At least 19 recordsLinked to original sources
PubMed2006

Management of patients presenting with Sjogren's syndrome.

Sjogren's syndrome is an autoimmune exocrinopathy that predominantly affects salivary and lachrymal glands, leading to dry eyes and mouth. The most common clinical problems faced by the rheumatologist are those of dry eyes and mouth, parotid swelling, fatigue and extraglandular manifestations. The first stage in management is to make an accurate diagnosis based on the American/European consensus criteria. The most frequent differential diagnoses are dry eyes and mouth symptoms, a variant of chronic fatigue syndrome and fibromyalgia, and sialosis, which causes a non-inflammatory enlargement of the parotid glands. The mainstay of treatment for the sicca symptoms is local therapy, and that for the milder systemic symptoms is hydroxychloroquine. Steroids and immunosuppressive drugs are reserved for more severe extraglandular disease. In spite of intensive research in other systemic treatments including biologic therapies, there is limited evidence to support their use in routine clinical practice.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Glucose-6-phosphate isomerase is not a specific autoantigen in rheumatoid arthritis.

OBJECTIVE: To test the hypothesis that glucose-6-phosphate isomerase (GPI) is a novel autoantigen in RA. METHODS: Eighty-eight serum samples from 23 patients with rheumatoid arthritis (RA), 25 with Sjögren's syndrome, 20 with systemic lupus erythematosus and 20 healthy controls were tested by enzyme-linked immunosorbent assay (ELISA) using a commercially available, partially purified rabbit GPI as antigen. Beside each duplicate well containing antigen (10 micro g/ml), uncoated blocked duplicate wells (phosphate-buffered saline only) were included as controls for non-specific binding for every serum tested. We also examined antibodies binding to various polypeptides in the GPI preparation by immunoblotting in 73 of the sera. RESULTS: By ELISA, binding levels were low and there was no difference between serum from patients with RA, other rheumatic diseases and normal controls. By immunoblotting, antibodies binding to the GPI polypeptide were present in 70-80% of all groups tested. In addition, we showed that another polypeptide identified as phosphoglucomutase was also present in the preparation and reacted with human immunoglobulins. CONCLUSION: Our findings suggest that GPI is not a specific autoantigen in RA.

Antibodies↗
PubMed2000

Delta 32 deletion of CCR5 gene and association with asthma or atopy.

The CCR5-delta32 deletion polymorphism (CCR5-delta32) was investigated for linkage and association to asthma and atopy using two panels of nuclear families containing 1284 individuals. No statistically significant linkage to asthma/wheeze or atopy was observed in either of the two panels of families. Multiallelic transmission disequilibrium tests (TDT) of the combined data found no significant association for atopy (52 independent alleles transmitted, 51 non-transmitted) or asthma/wheeze (39 transmitted, 44 non-transmitted). Although functional evidence might suggest that CCR5 is a good candidate gene for atopic asthma, this study provides no genetic evidence from CCR5-delta32 polymorphism to support this hypothesis.

Alleles↗
PubMed1999

Detection of human retrovirus 5 in patients with arthritis and systemic lupus erythematosus.

OBJECTIVE: To examine whether human retrovirus 5 (HRV-5) infection is associated with autoimmune rheumatic disease. METHODS: DNA from patients with various disorders including inflammatory diseases and from normal subjects was tested by nested polymerase chain reaction (PCR) for HRV-5 proviral DNA. Positive results were confirmed by DNA sequencing. RESULTS: HRV-5 proviral DNA was detected in 53% of synovial samples from arthritic joints, in 12% of blood samples from patients with rheumatoid arthritis (RA), and in 16% of blood samples from patients with systemic lupus erythematosus. In contrast, it was not detectable by PCR of affected tissues from patients with several other autoimmune diseases and was found in only 1 of >200 tissue specimens obtained at autopsy from non-RA patients. Sequence analysis of the amplified viral segment showed genetic variation between samples with maintenance of the open reading frame, typical of a replicating infectious retrovirus. CONCLUSION: This is the first report of the frequent detection of HRV-5 in any disease. We propose that the possible involvement of HRV-5 in autoimmune and rheumatic disease should be investigated further.

Arthritis, Rheumatoid↗
PubMed1999

Human retrovirus-5 in rheumatic disease.

It has long been suggested that retroviral infection may play a role in the pathogenesis of autoimmune rheumatic disease. Particles resembling retroviruses have been reported in tissue from patients with Sjögren's syndrome, lupus and rheumatoid arthritis, and molecular mimicry between retroviral antigens and host proteins has been proposed as a mechanism of induction of autoimmunity. Since 1980, four distinct human infectious retroviruses have been discovered, HTLV-I, HTLV-II, HIV-1 and HIV-2. We recently cloned part of a new human retrovirus genome, designated human retrovirus-5 (HRV-5) and demonstrated that this is not endogenous and is therefore a novel infectious retrovirus. Because symptoms resembling arthritis, polymyositis and Sjögren's syndrome occur in individuals infected with HTLV-I and HIV-1, we investigated the possibility that HRV-5 was associated with idiopathic rheumatic disease. Using nested PCR, HRV-5 we demonstrated that proviral DNA was present in approximately 50% of synovial samples of arthritic joints and was also found in over 10% of blood samples of patients with rheumatoid arthritis and systemic lupus erythematosus. HRV-5 proviral DNA was not detectable in affected tissues of autoimmune diseases and was found in only one of over 200 tissues taken at autopsy from non-rheumatoid patients. Sequence analysis of the amplified viral segment showed genetic variation between samples with maintenance of the open reading frame typical of a replicating infectious retrovirus. Thus HRV-5 appears to be a human retrovirus found with a very low genome copy number in most tissues, but which is increased to detectable levels in inflamed joints and blood from patients with rheumatic disease. Whether HRV-5 is aetiologically important in these diseases remains to be determined.

Autoimmune Diseases↗
PubMed1999

Retroviruses: ancient and modern.

Retroviruses are transmitted in two distinct ways: as infectious virions and as 'endogenous' proviral DNA integrated in the germ line of their hosts. Modern infectious viruses such as HIV recently infected mankind from simian hosts, whereas human endogenous retroviral genomes have been present throughout old world primate evolution. Recently we have characterised novel retroviruses in humans and pigs. Human retrovirus 5 (HRV-5) is detected as an exogenous genome in association with arthritis and systemic lupus erythematosus. Porcine endogenous retroviruses (PERV) are carried in swine DNA but can be activated to produce virions that are infectious for human cells, which has implications for xenotransplantation. A brief account of HRV-5 and PERV is given here.

Animals↗
PubMed1999

ERV-3 envelope expression and congenital heart block: what does a physiological knockout teach us.

Congenital heart block is a serious condition with significant mortality due in most cases to the transplacental transfer of autoantibodies from an otherwise asymptomatic mother. Although SSA/Ro and SSB/La autoantibodies have been implicated, attention has focused recently on autoantibodies to envelope proteins of endogenous retrovirus-3 (ERV-3). We have recently identified in 1% of the caucasian population a natural knock out of ERV-3 due to a premature stop mutation generating a severely truncated form of the protein [corrected]. If a pregnant female homozygous for the truncated form of the ERV-3 carries a foetus expressing the entire protein, the mother might be expected to acquire high titre immunity, while the foetus homozygous for the truncated form would not be expected to immunise its mother. In order to test whether this naturally occurring model could shed light on the pathogenesis of CHB, we determined the status of the ERV-3 stop polymorphism in 12 mothers of CHB infants [corrected]. The fact that none was homozygous for the stop mutation tends to rule out a role for the stop polymorphism of the mothers in the generation of the CHB disease, but does not exclude that other polymorphisms might be involved [corrected].

Animals↗
PubMed1998

Viral studies in rheumatic disease.

Rheumatic disease has long been thought to represent an interaction between environmental agents on a background of genetic susceptibility. In this review herpesviruses and retroviruses are considered as possible aetiological agents in autoimmune disease with a particular emphasis on Sjögren's syndrome. A possible role for cytomegalovirus, Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6) and human herpesvirus-8 (HHV-8) is reviewed. We conclude that there is no compelling evidence for the involvement of any of these herpesviruses. Retroviruses, however, are attracting increasing interest. In Man, both Human immunodeficiency virus (HIV) and human T lymphotropic virus type I (HTLV-I) infections cause autoimmune phenomena, including Sjögren's syndrome and arthritis in a minority of infected individuals. Similar reactions to retroviral infection are also seen in animal models. A possible role for the newly described human retrovirus-5 (HRV-5) is discussed, though current evidence does not support a role in Sjögren's syndrome. Other autoimmune diseases are under investigation.

Animals↗
PubMed1998

A double blind placebo controlled trial of azathioprine in the treatment of primary Sjögren's syndrome.

OBJECTIVE: To establish whether there is a place for low dose azathioprine (AZA) as a disease modifying agent in patients with uncomplicated primary Sjögren's syndrome (SS). METHODS: Twenty-five patients with primary SS were entered into a double blind, placebo controlled trial of AZA (1 mg/kg/day) for a period of 6 months. RESULTS: Six patients, all receiving active drug, withdrew because of side effects. There was no significant change in disease activity variables when measured clinically, serologically, or histologically. CONCLUSION: This trial suggests that low dose AZA does not have a role as a disease modifying agent in SS.

Antirheumatic Agents↗
PubMed1997

Human retrovirus-5 proviral DNA is rarely detected in salivary gland biopsy tissues from patients with Sjögren's syndrome.

OBJECTIVE: To examine whether human retrovirus-5 (HRV-5) infection is associated with Sjögren's syndrome. METHODS: Salivary gland DNA was tested by nested polymerase chain reaction (PCR) for HRV-5 proviral DNA. Rigorous precautions were taken to prevent false-positive results from PCR contamination. Positive samples were confirmed by testing with an additional independent set of primers and were then sequenced. RESULTS: Ninety-two samples were examined (55 from Sjögren's syndrome patients, 37 from non-Sjögren's syndrome patients), 2 of which were positive. One was from a patient who had sicca symptoms but who did not satisfy the criteria for a diagnosis of Sjögren's syndrome. The other was from a patient with secondary Sjögren's syndrome. Owing to the extremely low virus load in minor salivary glands, the number of HRV-5-infected patients may be underestimated. In total, 3 different sequences of HRV-5 were identified which were 98% identical to the original sequence but which displayed variations between and within individuals. CONCLUSION: This is the first study to systematically seek a disease association with HRV-5, although with this method, an association with Sjögren's syndrome was not identified.

Amino Acids↗