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Biomedical subjects

R N Maini

Publications and source records attributed to R N Maini.

At least 217 records · Page 12Linked to original sources
PubMed1989

Rapid clearance of the lupus antigen Sm is delayed by autoantibody: a possible mechanism of autoimmunity perpetuation.

Sm ribonucleoprotein complex was immunopurified and labelled with 125I. After i.v. injection into normal mice 125I-Sm was cleared with a half life of less than 3 min, mainly to the liver (54% at 15 min). With time there was a progressive reduction in liver uptake (13.3% at 1 h), and this was associated with the appearance of increasing amounts of trichloroacetic acid soluble 125I in serum, suggesting complete Sm catabolism. Injection of 125I-Sm as a preformed immune complex with human anti-Sm antibody was associated with slower antigen removal from the circulation (half life 15 min), more gradual liver uptake (27% at 1 hr), and less degradation products in the serum than after injection of antigen alone. These data suggest that release of 125I-Sm into the circulation is followed by specific organ uptake and antigen degradation. In the form of an immune complex, the rapid removal mechanism is impaired, and antigen persists in the circulation in an undegraded form. Simultaneous production of anti-Sm antibody and Sm antigen release following tissue destruction could lead to amplification of any primed immune response as a result of autoantigen drive in systemic lupus erythematosus.

Animals↗
PubMed1988

Preparative isolation of p67, A, B, B' and D from nRNP/Sm and Sm antigens by reverse-phase chromatography. Use in a polypeptide-specific ELISA for independent quantitation of anti-nRNP and anti-Sm antibodies.

The p67 (67 kDa) and A (33 kDa) polypeptides of nRNP/Sm antigen and the B, B' (28 and 29 kda) and D (16 kDa) polypeptides of 'free' Sm antigen were isolated and used in enzyme-linked immunoadsorbent assays (ELISA) for human autoantibodies. ELISA specificity was demonstrated using monoclonal antibodies. The ELISA using HPLC-purified polypeptides was found to be more sensitive than immunoblotting for detecting antibody. 86% of sera with precipitating anti-nRNP antibodies were positive in the ELISA, as were all sera with precipitating anti-Sm antibodies. Patients with rheumatoid arthritis (RA), Sjögrens syndrome (SS) and undifferentiated connective tissue disease (UCTD) had low levels of anti-p67 with a prevalence 11.6% and 18%, respectively, whilst patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) had high levels and prevalence rates of 55.2% and 80%, respectively. Anti-B or anti-D antibodies were detected at high levels in SLE (prevalence 30%) but were found rarely in UCTD and MCTD (prevalence 7% and 10%) and not at all in RA or SS sera.

Animals↗
PubMed1988

Immuno-electron microscopy of chondrocyte-derived cells in the rheumatoid cartilage-pannus junction.

Immuno-electron microscopy has been utilised to examine the cartilage-pannus junction in seven patients with rheumatoid arthritis. Using a monoclonal antibody, keratan sulphate was localised to cells with the ultra-structural appearance of fibroblasts within a transitional fibroblastic zone in the pannus in two cases. This confirms previous light microscopy evidence that this area (which is clearly separate from articular cartilage) contains cells which produce keratan sulphate, and strengthens the hypothesis that these cells are derived from cartilage rather than from the adjacent synovial membrane.

Antibodies, Monoclonal↗
PubMed1988

T cells expressing gamma delta chain receptors in rheumatoid arthritis.

Whereas the majority of T cells use alpha and beta chains to form their T-cell receptor, a small minority of T cells, which do not express the CD4 or CD8 surface markers, use other chains termed gamma and delta to form their receptor. Flow cytometry was performed on cells isolated from the blood and synovial joints of patients with rheumatoid arthritis. Monoclonals which recognise the gamma and delta chains were used to compare the proportion of TCR gamma delta cells in these sites. Approximately half the patients had more TCR gamma delta in the joints than in their blood and one newly diagnosed patient had high numbers of TCR gamma delta cells in both blood and joints. In this preliminary study it is not possible to evaluate the role of these cells in the disease process, but it is of interest that in some RA patients there is an overabundance of both T cells that arise early in ontogeny (TCR gamma delta cells) and B cells that arise early in ontogeny, the CD5 B cell.

Antibodies, Monoclonal↗
PubMed1988

Autoimmunity to La (SS-B) in vitro is related to HLA-DR3 in healthy subjects.

In patients with Sjögren's syndrome 50-90% of those who have anti-La (SS-B) in their serum are HLA-DR3 positive. To investigate the relation between DR3 and anti-La antibody production 18 healthy subjects were divided into nine pairs, each matched for age and sex, containing one DR3 positive individual and one with a different DR type. Peripheral blood mononuclear cells from each pair were cultured with varying doses of pokeweed mitogen and supernatants from nine day cultures assayed for antibodies to La, nRNP/Sm, and DNA by enzyme linked immunosorbent assay (ELISA) using purified antigens. In each case peak anti-La secretion was greater in the DR3 positive subject than in the matched DR3 negative individual; in contrast, there was no consistent difference in levels of anti-DNA or anti-nRNP/Sm secretion. This specificity of enhanced autoantibody response in healthy individuals after polyclonal activation suggests that anti-La production may be under the control of genes linked to DR3.

Adult↗
PubMed1988

Specificity of anti-Sm antibodies by ELISA for systemic lupus erythematosus: increased sensitivity of detection using purified peptide antigens.

Sm antigen was purified by immunoaffinity chromatography using a murine monoclonal anti-Sm antibody and was confirmed to be free from contaminating polypeptides. This was then used to detect anti-Sm antibodies in patients' sera by enzyme linked immunosorbent assay (ELISA). Antibodies against Sm were detected in only 9/52 (17%) patients with systemic lupus erythematosus (SLE) by immunodiffusion, but 15/52 (29%) were positive for IgG anti-Sm antibodies by ELISA. The presence of anti-Sm antibodies remained disease specific despite the increase in sensitivity of this assay and validates its potential use for clinical application. There was no correlation between the presence of anti-Sm antibodies and any clinical features of SLE. In 23 renal biopsies a membranous component to the glomerulonephritis correlated with anti-Sm antibodies (p less than 0.05). Patients from West Africa, the Carribean Islands, and Asia had a higher prevalence of anti-Sm antibodies than the local Caucasian population.

Antibody Specificity↗
PubMed1988

Increased concentrations of proteoglycan components in the synovial fluids of patients with acute but not chronic joint disease.

Synovial fluid samples (139) from 121 patients with rheumatoid arthritis, osteoarthritis, pseudogout, chronic pyrophosphate arthritis, gout, and reactive arthritis were analysed for cartilage proteoglycan components. Keratan sulphate (KS) epitope was determined by a competitive radioimmunoassay, and total sulphated glycosaminoglycans (S-GAG) were determined after papain digestion by a specific dye binding assay. Increased concentration of both KS epitope and S-GAG were found in synovial fluid from joints with acute inflammatory arthropathy (gout, pseudogout, and reactive arthritis). Analysis of consecutive samples from the same joint at different stages showed that the concentration of KS epitope or total S-GAG varied with acute inflammatory activity. In samples from patients with chronic conditions during active and inactive inflammatory phases concentrations were much lower and not distinguishable among these disease groups. The detection of raised concentration of proteoglycan components may reflect the rapid depletion or greatly increased turnover of proteoglycan in the articular cartilage during acute inflammation in the joint. This did not appear to be sustained in most patients with chronic joint diseases.

Acute Disease↗
PubMed1988

Reaction of antibodies to rheumatoid arthritis nuclear antigen with a synthetic peptide corresponding to part of Epstein-Barr nuclear antigen 1.

Antibodies to rheumatoid arthritis nuclear antigen (RANA) are detected by immunodiffusion (ID) and immunofluorescence (IF), though reports of the identity of the antigen(s) have been conflicting. In this study it is shown conclusively that ID and IF anti-RANA react with epitopes on Epstein-Barr nuclear antigen 1 (EBNA-1) and that the major epitope detected by immunofluorescence is represented by a synthetic peptide, P62, corresponding to part of EBNA-1. In an enzyme linked immunosorbent assay (ELISA) anti-P62 antibodies in 35 rheumatoid arthritis sera were threefold higher than those of 35 age and sex matched controls, with the highest levels occurring in young patients with active joint disease.

Adult↗
PubMed1988

The first international standard for antibodies to double stranded DNA.

This paper announces the availability of the first international standard for anti-double-stranded DNA (anti-dsDNA). The material, coded Wo/80, was obtained after recalcification of plasma taken from a patient with systemic lupus erythematosus. Vials were filled with 500 microliters serum and freeze dried. The serum contains no other autoantibodies in measurable quantities. The vials should be stored at -20 degrees C. The standard should be used for establishing national, regional, or local standards. In eight laboratories satisfactory results with the immunofluorescence technique on Crithidia luciliae were obtained; the titres varied between 1/20 and 1/640 (mean 1/160). In seven laboratories the Farr assay, with the so called 'Amersham kit', was performed. At a dilution of 1:40 a mean binding percentage of about 50% was observed. After reconstitution with 500 microliters of distilled water, the vial contains 100 IU/500 microliters or 200 IU/ml. The standard can be obtained from the custodian of WHO: Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, PO Box 9190 1006 AD Amsterdam, The Netherlands.

Antibodies, Antinuclear↗
PubMed1988

Representative sample of rheumatoid synovium: a morphometric study.

The synovium from 11 patients with rheumatoid arthritis, who were undergoing joint surgery, was assessed using histological and morphometric techniques. Histological examination confirmed previous reports that the intensity of the cellular reaction varied throughout the synovium, and the morphometric method reflected this variability sensitively. The method was shown to be reproducible and allowed areas of similar cellular density to be defined. From these defined areas a total of 2.5 mm2 of synovium equivalent to 12 fields at x250 required analysis to reflect the variation in the cellular reaction. It would be feasible to collect this amount of material using an arthroscope.

Arthritis, Rheumatoid↗
PubMed1988

Morphometric comparison of synovium from patients with osteoarthritis and rheumatoid arthritis.

Synovium was collected from 15 patients who were undergoing joint surgery. Two groups were defined by clinical diagnosis: patients with primary osteoarthritis (n = 4); and those with rheumatoid arthritis (n = 11). The synovium was studied using histological and morphometric techniques. In agreement with previous studies, no histological features specific for either diagnosis were found. A previously validated morphometric method was used to estimate the cellular density of randomly picked fields within defined areas of synovium. The mean nuclear density of cellularity of comparable areas of synovium was significantly different between these two disease states, but the mean nuclear density between individual representative samples within each clinical group was homogeneous. The morphometric analysis of lymphocyte subsets showed that within the upper synovial region and cellular aggregates in osteoarthritis, the distribution of T cells expressing the CD4 and CD8 antigen was the same. In rheumatoid arthritis CD8 cells predominated in the upper synovial region and CD4 cells in the cellular aggregates. Plasma cells were rarely found in osteoarthritic synovia, but were common in rheumatoid arthritis, with IgG-producing plasma cells predominating. Morphometric studies of representative synovial samples may help to improve histological diagnosis and our understanding of pathological mechanisms.

Aged↗
PubMed1988

Phenotypic and functional features of CD5+ B lymphocytes in rheumatoid arthritis.

Using flow cytometry B lymphocytes expressing CD5 were increased in the blood of 15 out of 31 patients with rheumatoid arthritis (RA). In contrast to the monoclonal CD5+ B lymphocytes in patients with B-chronic lymphocytic leukaemia, CD5+ B cells from RA patients and neonatal cord blood are polyclonal as demonstrated by kappa/lambda expression. These B cells co-express mu and delta heavy chains and are CD19, CD20, CD21 positive. Purified CD5+ and CD5- B cells appeared of similar size and granularity as judged by light scatter values. Staphylococcus aureus C stimulated cord blood B cells showed loss of CD5 antigen following activation and production of similar amounts of IgM-rheumatoid factor (RF). EBV stimulation of purified RA B subsets lead to greater production of IgM-RF by CD5+ B cells than by CD5-B cells suggesting an enrichment of precursor cells in this fraction.

Antigens, Differentiation↗
PubMed1988

Co-existent anti-La antibodies and rheumatoid factors bear distinct idiotypic markers.

This study describes the distribution of isotypes and idiotypes of two autoantibody populations, anti-La and rheumatoid factor, which co-exist in both the sera and saliva of patients with primary Sjögren's syndrome. The two autoantibodies are distinguished not only by their antigenic specificity but also by the nature of their idiotypic markers. IgA anti-La antibodies bearing restricted idiotypes are specifically enriched in saliva compared to serum suggesting their local synthesis. In contrast, rheumatoid factors bear cross-reactive idiotypes and may arise as a direct consequence of the secondary immune response.

Antibodies↗
PubMed1988

Role of HLA class II and cytokine expression in rheumatoid arthritis.

HLA class II expression is notable in rheumatoid arthritis. We have investigated the mechanism of HLA class II regulation in the joints and found local synthesis, as judged by mRNA levels to be high. The role of antigen presentation in maintaining class II mRNA was explored, and blocking presentation by using monoclonal antibodies to HLA class II inhibited synthesis of mRNA for HLA-DR alpha chain. HLA class II expression is maintained by cytokines and so cytokine production in rheumatoid joints was investigated. It was chosen to use mRNA analysis by slot blotting as a screening assay, and the expression of many cytokines was detected. Levels of these were maintained in culture in the absence of extrinsic stimulation.

Antibody Formation↗