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Biomedical subjects

R N Maini

Publications and source records attributed to R N Maini.

At least 271 records · Page 15Linked to original sources
PubMed1985

IgG antibodies to SS-B (La), RNP/Sm and DNA are produced by PWM-stimulated normal human lymphocytes in culture.

Peripheral blood lymphocytes from five healthy subjects and three patients with Sjögrens syndrome and systemic lupus erythematosus were stimulated with pokeweed mitogen to examine the effects of polyclonal activation on the secretion of autoantibodies in health and disease. Antibodies to SS-B (La), RNP/Sm and DNA were detected in supernatants from cultures from healthy controls, in some cases approaching levels secreted by the patients. All secreted autoantibodies were of IgG class and the antigen specificity of the secreted anti-SS-B was proven by cross-adsorption experiments. Our results extend the range of defined specificities of autoreactive B cells in healthy individuals. These data argue against a case for physiological deletion of autoreactive B cell clones and support theories of their active recruitment in autoimmunity.

Adult↗
PubMed1985

A seroepidemiological study of cytomegalovirus and Epstein-Barr virus in rheumatoid arthritis and sicca syndrome.

Antibodies to cytomegalovirus (CMV) and Epstein-Barr virus capsid antigen (EBVCA) were examined in 41 patients with rheumatoid arthritis (RA), 26 patients with primary sicca syndrome, and 26 healthy subjects of similar age and sex. IgG antibody titres to EBVCA and CMV were similar in all three groups, apart from a trivial increase of antibodies to EBVCA in RA. False positive IgM anti-CMV antibodies detected in serum from one patient with sicca syndrome and 20 patients with RA were shown to be due to rheumatoid factors. These data did not support recent suggestions that patients with these diseases showed exaggerated immunological responses to either virus and emphasised the need to incorporate adequate laboratory and disease controls when seroepidemiological studies are performed on sera containing rheumatoid factors and autoantibodies.

Adult↗
PubMed1985

Circulating immune complexes and rheumatoid arthritis: a comparison of different assay methods and their early predictive value for disease activity and outcome.

The performance of four different assays for circulating immune complexes-the C1q solid phase method, one using protein A and one using anti-IgG, C1q PEG, and the 2% PEG method-were compared in 61 patients with early rheumatoid arthritis followed up for two years. There were weak but statistically significant correlations between the results from some of the pairs of assays, but the changes over time from any single assay did not correlate with those from any of the other assays. None of the assays predicted either future disease activity, as measured by subsequent ESR, CRP, and articular index; or functional outcome, as measured by wrist extension, Steinbocker functional capacity, and the Stanford health assessment questionnaire. It is unlikely therefore that the measurement of immune complexes is of value in predicting early outcome in patients with rheumatoid arthritis.

Adult↗
PubMed1985

Characterisation of non-histone nuclear proteins cross reactive with purified rheumatoid factors.

In order to examine the interactions between isolated rheumatoid factors (RFs) and cell nuclear antigens we have prepared 10 RFs by affinity chromatography against IgG coupled to Sepharose. Of these, seven cross reacted with cell nuclei on indirect immunofluorescence. The nuclear antigen appeared to be DNA histones by indirect immunofluorescence on rat liver, though on immunoblotting the rheumatoid factors also reacted with three non-histone polypeptides which were identified in the soluble fraction of nuclear extracts. We were unable to show any relationship between these polypeptides and rheumatoid arthritis nuclear antigen. These reactions represent a hitherto unrecognised phenomenon, which extends the range of antigens recognised by rheumatoid factors. We suggest that the immunopathogenic significance of RFs may not be restricted to their reactivity with IgG, and that non-histone nuclear proteins merit further investigation.

Antigens, Nuclear↗
PubMed1985

MRL mice show an age-related impairment of IgG aggregate removal from the circulation.

The fate of heat-aggregated human IgG (HAGG) was examined in young and old autoimmune MRL-lpr/lpr and MRL-+/+ mice and compared to BALB/c mice of different ages. Following iv injection of [125I] HAGG the older MRL-lpr/lpr and MRL-+/+ mice showed impaired hepatic and splenic uptake of this material. In addition the clearance rate of HAGG was significantly slower in the older MRL-lpr/lpr mice (t1/2 = 50 min) when compared to younger controls (t1/2 = 13 min) although this age-related retardation of clearance was not observed in the MRL-+/+ mice. No difference was seen in the clearance rate or organ uptake studies of the two age groups of BALB/c mice. Catabolic studies using trichloracetic acid suggested that the HAGG was catabolized to smaller fragments with time but not to such a great extent in the older diseased animals, again no age-related difference was seen in the BALB/c mice. Our studies suggest that with age both autoimmune strains of MRL mice show some saturation of the mononuclear phagocytic system (MPS) and that this process is more obvious in the MRL-lpr/lpr mice. MPS saturation may play a role in the pathogenesis of autoimmune disease in these mice.

Aging↗
PubMed1984

Identification and purification of a 55K polypeptide in Sjögren's syndrome A antigen.

The Sjögren's syndrome A antigen (SS-A) purified by affinity chromatography from human spleen was shown to contain a major polypeptide with a mol. wt. of 55 000 daltons confirmed as SS-A by its reactivity with different anti-SS-A sera on affinity columns, immunodiffusion and the Western blot. A similar reactive polypeptide was demonstrated in extracts of rabbit liver, brain, spleen, kidney, lung and thymus.

Animals↗
PubMed1984

Tissue uptake and catabolic studies of 125I SS-B (La) injected into mice.

The radiolabeled soluble cellular antigen 125I SS-B (La) has a plasma half-life of 3 min following iv injection into BALB/C mice. Uptake by Kupffer cells (KC) and proximal renal tubular (PRT) cells was demonstrated by autoradiography (ARG). That trichloracetic acid (TCA)-soluble products of 125I SS-B appeared in plasma within 1 min of iv injection suggests rapid in vivo breakdown. Activated peritoneal macrophages (APM) degraded 125I SS-B in a time- and cell-dose-dependent fashion. These findings suggest that the plasma clearance and catabolism of 125I SS-B may be dependent on its interaction with phagocytic cells. This rapid antigen elimination may protect against harmful autoantibody responses.

Animals↗
PubMed1984

HLA antigen associations with extra-articular rheumatoid arthritis.

Seventy-seven patients with rheumatoid arthritis were investigated to examine the frequency of HLA antigens and their relationship to clinical and serological manifestations of extra-articular disease. The phenotype frequencies of DR4, DRw53, Bw62 and Cw3 were significantly increased, compared to normal controls, and there were negative associations with DR2 and DR7. The HLA antigen in strongest association with rheumatoid arthritis was DR4 (73.6%) and the relationship with DRw53 appeared to be secondary. The frequency of DR4 rose to 92% in seropositive patients with extra-articular disease manifestations whose serum contained immune complexes. A high frequency of DR4 was also seen in male patients (86%), reaching 100% in the small group of seropositive male patients with immune complexes. It is suggested that extra-articular disease represents a manifestation of severe classical rheumatoid arthritis and is not an 'overlap' syndrome. We propose that the HLA haplotype Cw3-Bw62-Dw4-DR4-DRw53 makes a greater genetic contribution to disease susceptibility in both extra-articular and male rheumatoid arthritis patients than in other subsets of RA.

Arthritis, Rheumatoid↗
PubMed1984

Differences in immunochemical characteristics of cryoglobulins in rheumatoid arthritis and systemic lupus erythematosus and their complement binding properties.

Cryoglobulins isolated from sera of patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were analysed for their immunoglobulin, antibody, and complement components. In both disease categories the cryoglobulins contained predominantly IgG with lesser amounts of IgM and IgA, but relative to serum more IgM was concentrated in the cryoglobulins. IgM rheumatoid factor was found in 65% of RA cryoglobulins but in only 17% of SLE cryoglobulins (p less than 0.02), whereas SLE cryoglobulins contained more DNA binding activity than RA cryoglobulins (p less than 0.01). C1q binding activity was detectable in the majority of SLE and RA sera and SLE cryoglobulins. Paradoxically only two out of 34 RA cryoglobulins bound C1q, although rheumatoid factor activity was present in both cryoglobulins and sera. When isolated from serum the rheumatoid factor fraction strongly bound C1q. Both RA and SLE cryoglobulins contained similar small amounts of C3 and C4. Differences in antibody composition and complement binding activity of cryoglobulins from RA and SLE sera may reflect properties of immune complexes which affect their tissue localisation and pathogenicity.

Antibodies, Antinuclear↗
PubMed1984

Definition and clinical relevance of antibodies to nuclear ribonucleoprotein and other nuclear antigens in patients with cryptogenic fibrosing alveolitis.

Antinuclear antibodies (ANA) were studied in 122 patients with cryptogenic fibrosing alveolitis (CFA) and compared with age- and sex-matched control subjects. Fluorescent ANA were detected in 32% of the patients and showed a correlation with the presence of a systemic connective tissue disease; ANA were present in 6% of the control subjects, 21% of the patients with CFA alone, and 46% of those with CFA and an associated connective tissue disease. Antibodies to the defined nuclear antigens: deoxyribonucleic acid (DNA), nuclear ribonucleoprotein (nRNP), the Sm antigen, and Sjögren's syndrome A and B antigens (SS-A and SS-B) were examined to establish whether their presence was diagnostic of the associated diseases. Antibodies to DNA and Sm antigens identified 3 patients with CFA and systemic lupus erythematosus. The frequency of antibodies to SS-A and SS-B did not differ from that in control subjects. Antibodies to nRNP, detected in 15 (12%) of the patients (at a high titer in 5), were associated with females, the presence of Raynaud's phenomenon, and rheumatoid factor in the serum. However, despite the detection of these antibodies, none of these patients met fully the proposed criteria for the diagnosis of mixed connective tissue disease.

Adult↗
PubMed1984

Specific autoantibody slows the rapid plasma clearance of 125I-SS-B (La) in mice.

In BALB/c mice the plasma clearance of intravenously (i.v.) injected 125I-SS-B (La) (T 1/2 = 3 min) is markedly delayed when complexed in vitro to specific autoantibody (T 1/2 = 60 min) and is associated with diminished hepatic and renal uptake. The in vivo behaviour of 11S 125I-SS-B-IgG-anti-SS-B complexes was similar to that of 20-30S 125I-heat-aggregated IgG. The presence of anti-SS-B antibodies in systemic lupus erythematosus and Sjögren's syndrome could similarly result in persistence of SS-B containing immune complexes and provide a mechanism which may perpetuate autoimmunity.

Animals↗
PubMed1983

Quantitation and detection of isotypes of anti-SS-B antibodies by ELISA and Farr assays using affinity purified antigens. An approach to the investigation of Sjögren's syndrome and systemic lupus erythematosus.

Affinity purified SS-B was characterized as a protein with immunoreactive polypeptides of 40K and 29K. A modified Farr assay and an enzyme linked immunosorbent assay (ELISA) were 100- to 1,000-fold more sensitive than immunodiffusion and showed an association with the systemic manifestations of primary sicca syndrome and Sjögren's syndrome with systemic lupus erythematosus. The ELISA was sufficiently sensitive to detect class specific antibodies in saliva and lymphocyte culture supernatants.

Adult↗
PubMed1983

Relationship of precipitating antibodies to soluble cellular antigens and histologically defined renal lesions in systemic lupus erythematosus.

Antibodies to nuclear ribonucleoprotein (nRNP), Sm, SS-A, and SS-B, were studied by a quantitative immunodiffusion technique in 48 patients with systemic lupus erythematosus (SLE). There was no correlation between the presence or titre of antibodies to any of these antigens and clinically apparent renal disease. However, among 34 patients who had renal biopsies antibodies to nRNP, Sm, and/or SS-A were seen in all 8 patients with membranous glomerulonephritis. Low-titre antibodies (less than 1:4) were seen in 3 out of 7 patients with diffuse proliferative glomerulonephritis. Longitudinal studies in 4 patients who had serial biopsies indicated that the association between serological and histological findings was maintained for prolonged periods. In 2 patients whose biopsy pattern changed, antibodies to nRNP, Sm, and SS-A antedated the development of membranous nephritis.

Antigens↗
PubMed1983

Failure of captopril to reverse the renal crisis of scleroderma.

Captopril, an oral inhibitor of angiotensin converting enzyme, has recently been described as causing a dramatic reversal of the renal crisis in scleroderma in 2 patients(1). We report here 2 patients with scleroderma, hypertension, and rapidly deteriorating renal function who were given captopril. Despite good blood pressure control, captopril had no effect on renal function, both patients requiring long-term haemodialysis.

Captopril↗
PubMed1983

Purification and characterization of the Sjögren's syndrome A and B antigens.

In sera from patients with systemic lupus erythematosus and Sjögren's syndrome (SS), antibodies are present in high titres to small cellular proteins which may be involved in RNA processing. In this study we used affinity chromatography with antibodies isolated from patients sera to purify two cellular antigens; SS-A (Ro) from human spleen and SS-B (La) from rabbit thymus. Both antigens co-purified as a molecular complex from human thymus. The protein components were acidic though SS-A was resistant, and SS-B sensitive to trypsin. On polyacrylamide gel electrophoresis SS-A migrated as a single 55K polypeptide and SS-B as 40-45K polypeptides with a 29K degradation product. All of these polypeptides were reactive in the western blot with their respective antibodies from characterized sera and similar components in SS-B were demonstrated in tissue extracts from a range of mammalian species. These purified antigens represent important reagents for the investigation of the aetiology of some types of autoimmunity.

Animals↗