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Biomedical subjects

R N Maini

Publications and source records attributed to R N Maini.

At least 235 records · Page 13Linked to original sources
PubMed1988

Cells and matrix expressing cartilage components in fibroblastic tissue in rheumatoid pannus.

Our studies of the cartilage-pannus junction in rheumatoid joints have demonstrated the frequent presence of a transitional fibroblastic zone (TFZ) overlying articular cartilage. Using immunohistochemical techniques this zone has been shown to contain cells and matrix expressing specific cartilage components but not antigens present on cells in invasive vascular pannus. These findings support the concept that fibroblastic pannus is derived from the underlying articular cartilage rather than adjacent tissues. This type of reaction involving a metaplastic change in the chondrocyte is particularly common in large weight-bearing joints and may represent a different mechanism of cartilage degeneration to the classically described direct invasion of cartilage by hypertrophic synovial tissue.

Arthritis, Rheumatoid↗
PubMed1988

The significance of CD5+ B cells in rheumatic diseases.

The presence of autoantibodies in rheumatoid arthritis (RA) and primary Sjögren' syndrome (SS) is a feature of these diseases. Because of the probable role of autoantibodies in the pathogenesis of RA and primary SS, the study of the origin and regulation of B lymphocytes producing autoantibodies is of special importance. In mice, B lymphocytes can be divided into two populations of distinct lineages, the conventional bone marrow-derived B subset and the self-renewing peripheral subset. B lymphocytes of the latter express an antigen initially described as T cell specific, the Ly-1 or CD5 antigen. In human, such CD5+B cells are found in foetal lymphoid tissue but their frequency diminishes in adult life. We have found a significant increase in CD5+B cells in the peripheral blood of patients with RA and primary SS, and a small family study of relatives of two RA patients suggests that such 'high phenotype' could be a genetic trait. Furthermore, CD5+B cells appear enriched in autoantibody-producing cells since they produce IgM-rheumatoid and other autoantibodies when suitably activated in vitro. Our current hypothesis is that persistence of high numbers of CD5+B cells in adulthood may predispose to chronic inflammatory arthritis due to the reactivity of the antigen receptor of these cells with a variety of autoantigens in the joint. Such reactivity would allow an autoimmune reactions causing the perpetuation of chronic inflammation at the disease site.

Arthritis, Rheumatoid↗
PubMed1988

C-reactive protein in haemodialysis patients with dialysis arthropathy.

Increased plasma C-reactive protein was found in one-third of 99 patients on maintenance haemodialysis and there was a significant correlation between C-reactive protein and years on haemodialysis. Patients with dialysis arthropathy had a significantly higher mean C-reactive protein than the patients with no joint symptoms. Our results suggest that chronic inflammatory reactions occur in long-term haemodialysis patients and that dialysis arthropathy may have an inflammatory basis.

C-Reactive Protein↗
PubMed1988

Anti-idiotypic induced suppression of Sjögren's syndrome associated anti-La autoantibody secretion in vitro.

Peripheral blood mononuclear cells from patients with Sjögren's Syndrome spontaneously secrete autoantibodies to the La antigen when cultured in vitro. This paper reports that specific IgG autoantibody production in vitro is suppressed by pre-treatment of CD8+ enriched T cells with rabbit polyclonal antibodies to idiotypes borne by circulating autologous anti-La antibodies. Treatment of this T cell subpopulation with anti-idiotypes specific for circulating anti-La antibodies from other patients or for anti-DNA antibodies was without effect on anti-La antibody production. Similarly anti-La anti-idiotypes had no effect on the production of autoantibodies to other ribonucleoprotein antigens such as nRNP/Sm. These data show that CD8+ T cells are the main targets for anti-idiotypic control in vitro. We suggest that the relative deficit of these cells, plus a surfeit of CD4+ T cells at the site of the pathological lesion within the salivary gland permits localized production of autoantibodies. Thus, dysregulation of the idiotypic network could contribute to the pathogenesis of Sjögren's Syndrome.

Antibodies, Antinuclear↗
PubMed1988

Anti-nRNP anti-nuclear antibody-secreting cells are represented in the B-lymphocyte repertoire of normal and MRL/MP-lpr/lpr lupus mice.

Spleen cells from MRL-lpr/lpr, CBA and BALB/c mice were cultured in vitro and assayed for production of anti-nuclear antibodies. Spleen cells from all species produced IgM antibodies to a nRNP (U1-RNP)-specific antigen and to double-stranded DNA (dsDNA) after stimulation with LPS. The specificity of the anti-nRNP antibodies was shown, by immunoblotting, to be directed against the 33,000 MW polypeptide of nRNP/Sm. CBA mice produced more IgM autoantibody in vitro than MRL/lpr or BALB/c mice. In contrast, IgG anti-nRNP and anti-dsDNA antibody were not produced by any of the strains. Our data show that anti-nRNP and anti-dsDNA precursor B cells are part of the normal murine immune repertoire and are not confined to the MRL/lpr strain. This suggests that the spontaneous development of anti-nRNP and anti-dsDNA antibodies associated with systemic lupus erythematosis (SLE) is dependent on clonal stimulation and removal of suppressive influences.

Animals↗
PubMed1988

Spontaneous recovery of the decreased expression in vitro of interleukin 2 receptors in rheumatoid arthritis.

Peripheral blood mononuclear cells (PBM) from 11 patients with rheumatoid arthritis (RA) stimulated with 0.13 and 0.25 microgram/ml phytohaemagglutinin (PHA) for 3 days showed a depressed expression of interleukin 2 receptor (IL-2R) when compared with 14 normal controls (P less than 0.01). At these two doses of PHA a depressed lymphocyte proliferative response was also observed (P less than 0.01). However the kinetics of the response of the RA group differed from those of the control group. Whereas by day 6 IL-2R expression and lymphocyte proliferation in the control group was decreased compared with day 3, responses of the RA cells were increased. Following stimulation with the higher dose of PHA (1 microgram/ml) the kinetics of lymphocyte proliferation and IL-2R expression were equivalent in control and RA cultures. These results demonstrate that the impaired IL-2R expression and lymphocyte proliferation observed with sub-optimally stimulated PBM from RA patients is spontaneously reversed during prolonged culture and is consistent with the hypothesis that there is a lack of available IL-2 in the early stages of culture.

Arthritis, Rheumatoid↗
PubMed1988

Heterogeneity of T cell receptor idiotypes in rheumatoid arthritis.

The nature of the T cell response in the rheumatoid synovium was investigated by using monoclonals MX9 and 42/1C1, which recognize the V beta 8 and V beta 5 T cell receptor gene families respectively. The blood and synovial T cells of ten patients with rheumatoid arthritis were compared. The majority (8/10) had different numbers of V beta 5 and V beta 8 cells in the joints from those in the blood, indicating that the T cells in the joints were not a sample of those in the blood. In three patients both V beta 5 and V beta 8 cells in the joint were augmented in number, suggesting that the T cells selectively retained in the joint were not members of a single clone, but derived from many clones. Some patients had increased levels of V beta 5 or V beta 8 alone in the joint indicating that heterogeneity existed between patients. These results are not consistent with the preferential or dominant use of a single V beta gene family in the T cells involved in the rheumatoid arthritic joints.

Arthritis, Rheumatoid↗
PubMed1988

Interleukin-1 and tumour necrosis factor mRNA expression in rheumatoid arthritis: prolonged production of IL-1 alpha.

In rheumatoid arthritis there is a chronic immune and inflammatory reaction which can lead to the destruction of the diseased joint. Cytokine gene expression was studied in synovial cells using cDNA probes specific for human interleukin 1 (IL-1), -alpha and IL-1 beta, tumour necrosis factor (TNF), -alpha and TNF beta (lymphotoxin); protein molecules which induce cartilage degradation and bone resorption. In all cases studied, IL-1 mRNA was present in freshly isolated synovial cells from fluid or membrane. Compared to levels of IL-1 mRNA found in optimally activated normal blood mononuclear cells, the levels of IL-1 alpha mRNA were high in seven of the nine patients studied, whereas IL-1 beta mRNA, the dominant form in blood, was relatively lower. TNF alpha and TNF beta mRNA were also detected. Rheumatoid synovial cells, cultured without any stimulus, continued to express high levels of IL-1 alpha mRNA for up to 5 days, compared to the 24 h response of activated blood cells; IL-1 beta mRNA in culture was also prolonged. Cultures of rheumatoid joint cells produced IL-1 bioactivity, with roughly equal amounts of IL-1 alpha and beta, as assessed using neutralizing antibodies. TNF bioactivity was also detected which may be of importance as TNF induces the production of IL-1. The finding of these mediators produced in large amounts in active rheumatoid synovial cells suggests that mutually stimulatory cell interactions, mediated by these molecules, may be important in the chronic inflammation and tissue destruction in rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1987

Purification of human autoantibodies from cross-linked antigen immunosorbents.

A method is described whereby autoantibodies to the Sjögren's syndrome antigen La (SS-B) can be purified from re-usable immunosorbent columns constructed from covalently linked human autoantibodies to which the antigen is cross-linked. Previous attempts to link the antigen directly to CNBr-Sepharose beads resulted in loss of biological activity and thus each purification of antibody required fresh batches of antigen. The present technique is a significant improvement since the cross-linked immunosorbents prepared from a single batch of antigen can be re-used several times over a 6 month period. Furthermore F(ab')2 fragments of anti-La antibodies can be purified from pepsin-digested serum samples. These antibodies react in ELISA, Western blot and immunofluorescence in an identical way to serum and murine monoclonal anti-La antibodies and show no reaction with the Ro antigen. However, being of human origin the affinity-purified anti-La antibodies have the advantages of bearing the same idiotypes and reacting with the same antigenic epitopes as naturally occurring serum autoantibodies.

Autoantibodies↗
PubMed1987

Chondrocyte-derived cells and matrix at the rheumatoid cartilage-pannus junction identified with monoclonal antibodies.

In the cartilage-pannus junction of 14 patients with rheumatoid arthritis (RA) and seven patients with osteoarthritis (OA), monoclonal antibodies to keratan sulphate (KS) and chondroitin sulphate (CS) stained a transitional fibroblastic zone (TFZ) within the pannus in nine RA patients and one OA patient. In three patients this was clearly localised to the cytoplasm of cells in this zone, but in all remaining cases KS and CS could be demonstrated in the surrounding matrix. This area was distinguished from adjacent pannus which contained many blood vessels and cells positive for MHC Class II antigen. Specific markers for glycosaminoglycans have been employed to demonstrate that chondrocyte-derived cells and matrix contribute to the changes seen at the cartilage-pannus junction in RA-affected joints.

Adult↗
PubMed1987

Demonstration of an unidentified 48 kD polypeptide in circulating immune complexes in rheumatoid arthritis.

Circulating immune complexes (CIC) were isolated from 25 patients with rheumatoid arthritis (RA) by anti-C1q affinity chromatography. The components were detected by silver stained sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) gels and identified by the Western blot. The CIC were composed of 20 different polypeptides, including albumin, immunoglobulin, complement, and acute phase reactants. Two components (molecular weight 48 kD and 45 kD respectively) remained unidentified. The 48 kD polypeptide was found in CIC from six out of 14 patients (43%) with extra-articular RA, but from none of eight patients with vasculitic complications of other connective tissue diseases. All immunoreactants were more frequently found in the patients with extra-articular features of RA. Although these results emphasise that most CIC in RA are composed of endogenous proteins, the 48 kD polypeptide is a candidate for an extrinsic antigen in RA.

Antigen-Antibody Complex↗
PubMed1987

Autoimmunity in rheumatoid arthritis. An approach via a study of B lymphocytes.

In this article the relationship between the cellular elements of the immune response and inflammation are examined with reference to the B lymphocyte repertoire. Evidence is presented that, in addition to an environment in the joint that favors localization and activation of auto-reactive B lymphocytes, the circulating B lymphocyte pool in rheumatoid arthritis is abnormally enriched in cells that bear a receptor for mouse erythrocytes and possess CD5 antigen. B lymphocytes with these novel phenotypic markers secrete autoantibodies and are found in abundance in fetal lymphoid tissues and cord blood; analogous cells in the mouse belong to a distinct lineage and are implicated in allotype- and idiotype-restricted interactions. It is postulated that a subset of B lymphocytes is of primary importance in the etiopathogenesis of rheumatoid disease.

Arthritis, Rheumatoid↗
PubMed1987

MRL-lpr/lpr mice show an impairment of IgG aggregate removal which relates to parameters of disease activity.

MRL-lpr/lpr mice show an age-related impairment in the removal of heat-aggregated IgG (HAGG) from the circulation. The female mice, which have an earlier mortality than their male counterparts, clear HAGG more slowly than the male animals. Delay in clearance of this probe of mononuclear phagocytic system (MPS) function relates directly to high levels of circulating immune complexes (CIC) and to significant renal damage. In addition it relates indirectly to hepatic and splenic uptake of HAGG. MPS saturation plays a significant role in the pathogenesis of the disease seen in MRL-lpr/lpr mice.

Aging↗
PubMed1987

Differential induction of lupus associated antinuclear antibodies in MRL mice by monoclonal anti-Sm antibodies.

The effect of monoclonal autoantibodies on immunoregulation was investigated in MRL/MpJ-lpr/lpr mice. Passive transfer of KSm2 (a monoclonal IgG2a antibody directed against the 16 kD polypeptide of Sm) induced IgG antibodies to the other major immunoreactive polypeptides of Sm (28 and 29 kD) in all mice studied, and to polypeptides of the closely related antigen nRNP/Sm in 63% of the mice. In addition an increment in IgG anti-dsDNA antibodies, and in IgA and IgM anti-Sm antibodies, over control levels was observed. These effects were not due to polyclonal activation since anti-histone antibody levels were unaffected. Two other IgG2a monoclonal antibodies: KSm5 (directed against the 28 and 29 kD Sm polypeptides) and OX 12 (directed against an irrelevant antigen) failed to modulate the autoimmune responses of the mice in any way. These results demonstrate specific antibody-mediated connectivity between B cell clones producing autoantibodies against three distinct antigens.

Animals↗