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Biomedical subjects

D R Jayne

Publications and source records attributed to D R Jayne.

At least 37 records · Page 2Linked to original sources
PubMed1993

Anti-idiotype antibodies to anti-myeloperoxidase autoantibodies in patients with systemic vasculitis.

The presence of anti-idiotype antibody (anti-id) activity to anti-myeloperoxidase autoantibodies (anti-MPO) was measured by assessing binding of IgG in patients' sera to F(ab')2 fragments of polyclonal heterologous anti-MPO antiserum. Thirteen paired acute and remission sera and three groups of sequential sera from patients with systemic vasculitis were studied. The levels of anti-MPO fell as disease activity subsided with treatment. However, levels of anti-id activity against these anti-MPO rose as patients entered remission. This effect was still seen after controlling for binding to F(ab')2 constant regions and after polyethylene glycol precipitation of immune complexes. In the sequential studies, levels of anti-MPO and anti-MPO anti-id tended towards a reciprocal relationship. These observations point to dynamic interactions between autoantibody and complementary anti-idiotype antibodies in this system and a role for idiotypic networks in the regulation of anti-neutrophil cytoplasm antibodies.

Acute Disease↗
PubMed1993

Pooled intravenous immunoglobulin in the management of systemic vasculitis.

Investigation into the therapeutic use of intravenous immunoglobulin (IVIg) in systemic vasculitis was prompted by the detection of anti-idiotype antibodies reactive with ANCA in IVIg and the proven ability of IVIg to reduce the incidence of coronary artery aneurysms in Kawasaki disease. The efficacy and safety of IVIg (Sandoglobulin) was assessed in an open study of 26 patients with active systemic vasculitis. Eight weeks after IVIg 13 patients were in full and 13 in partial remission, clinical benefit was maintained in 18 twelve months later and was reflected by changes in C-reactive protein and ANCA.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1993

Clinical significance of anti-endothelial cell antibodies in systemic vasculitis: a longitudinal study comparing anti-endothelial cell antibodies and anti-neutrophil cytoplasm antibodies.

Ten patients with systemic vasculitis, all positive for anti-neutrophil cytoplasm antibody (ANCA), were followed for a mean of 36 weeks to determine the prevalence of anti-endothelial cell antibodies (AECAs) and the relationship between AECAs, ANCAs, and disease activity. Anti-endothelial cell antibodies were detected in eight (80%) patients at some time during the study. The levels of both AECAs and ANCAs changed with time, and these autoantibodies were present in 48% and 63% of the total 100 serum samples, respectively. Eighteen clinical remissions were observed; in 16 (88.9%) cases the level of ANCAs dropped. Fifteen (83.3%) of the 18 remissions were among the AECA-positive patients and the level of AECAs decreased in 13 (86.7%) instances (P = not significant). There were 11 episodes of disease relapse; all were associated with an increase in the level of ANCAs. Nine (81.8%) of the 11 relapses were among AECA-positive patients, and the level of AECAs increased in eight (88.9%) cases (P = not significant). Serum levels of AECAs appeared less suppressible by cyclophosphamide therapy compared with ANCAs, and patients who were persistently positive for AECAs despite being ANCA-negative during remissions were at risk of subsequent relapse. Disease recrudescense was not observed in patients persistently tested negative for both AECAs and ANCAs. Intravenous immunoglobulin therapy was used in four patients and resulted in clinical improvement in all cases, but with variable changes in the levels of AECAs and ANCAs. We conclude that AECAs are commonly detected in patients with systemic vasculitis and their levels show a relationship to disease activity similar to that for ANCAs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Influence of immunoadsorption on the removal of immunoglobulin G autoantibodies in crescentic glomerulonephritis.

We report the treatment of 5 patients with crescentic glomerulonephritis by immunoadsorption using a protein A column. Two had systemic vasculitis, 2 antiglomerular basement membrane disease and 1 systemic lupus erythematosus (SLE). In the patients with systemic vasculitis and SLE, there was successful removal of autoantibodies and rapid control of disease; remission was maintained over a mean follow-up of 2 years. Clinical improvement was not seen in 2 patients with anti-glomerular basement membrane (GBM) disease who presented with dialysis-dependent renal failure. There were no apparent clinical side-effects related to the immunoadsorption procedure. Protein A immunoadsorption offers a semiselective alternative to plasma exchange and appears to be safe and efficient in removing pathogenic autoantibodies in crescentic glomerulonephritis without anti-GBM antibodies.

Adolescent↗
PubMed1992

Analysis of anti-idiotypic antibodies against anti-microsomal antibodies in patients with thyroid autoimmunity.

Anti-microsomal antibody (AMA) activity was inhibited in 14 of 16 sera and in all 12 IgG preparations from patients with postpartum thyroiditis following incubation with F(ab')2 fragments from normal polyspecific immunoglobulin for therapeutic use (ivIg). Similar results were observed with sera from seven of seven patients with Graves' disease and five of six patients with autoimmune hypothyroidism. Results of these competitive binding assays and affinity chromatography of AMA IgG on Sepharose-bound F(ab'), fragments from ivIg indicated that AMA antibodies reacted with ivIg through idiotypic-anti-idiotypic interactions. Eight out of 10 IgG preparations from patients with autoimmune thyroid disease also showed inhibition of AMA activity when coincubated with autologous IgM at various IgG:IgM molar ratios. These observations suggest that ivIg can inhibit anti-microsomal antibodies through idiotype-anti-idiotype interactions and that such interactions occur with IgM anti-idiotype antibodies in vivo, providing evidence of a role for idiotypic network regulation in the control of thyroid autoimmunity.

Antibodies, Anti-Idiotypic↗
PubMed1992

Association of IgM with IgG ANCA in patients presenting with pulmonary hemorrhage.

ANCA are markers for systemic vasculitis such as Wegener's granulomatosis (WG) and microscopic polyarteritis (MPA) and are usually of the IgG isotype. However, IgM ANCA may rarely occur in isolation, and in these circumstances, we have found that they are associated clinically with a syndrome of pulmonary hemorrhage and systemic vasculitis. How frequently IgM ANCA may occur in conjunction with IgG has not previously been investigated. We report here a study of 24 consecutive patients with IgG ANCA-positive systemic vasculitis (14 WG, 10 MPA) in whom we determined whether IgM ANCA occurred in association with IgG ANCA, and if so, whether this had clinical importance. Eight patients were found to have IgM ANCA as well as IgG ANCA, and of these, seven presented with severe pulmonary hemorrhage. None of the IgM ANCA-negative patients presented with pulmonary hemorrhage. Although the occurrence of pulmonary hemorrhage in ANCA positive vasculitis was closely correlated with the presence of IgM ANCA, the antigen specificity of these IgM autoantibodies was variable, since both myeloperoxidase (4 patients), PR3 (3 patients), and an unknown ANCA antigen (1 patient) were found to be targets. We conclude that knowledge of ANCA isotype may have important clinical and therapeutic implications for the management of patients with systemic vasculitis.

Adolescent↗
PubMed1992

Anti-mitochondrial antibody IgG subclass distribution and affinity in primary biliary cirrhosis.

We have studied the total IgG subclass and anti-mitochondrial antibody (AMA) specific IgG subclass distribution in primary biliary cirrhosis (PBC) sera. In order to solve the problems caused by the differing affinities of subclass specific monoclonals and the competitive inhibition of antibodies in a whole serum assay, six sera were separated into subclass-specific fractions by affinity-depletion chromatography. AMA subclass distribution of 20 further sera from patients with PBC was assessed using conventional methods and the results were calibrated against one of the fractionated sera. Light chain distribution and AMA functional affinity were also assessed for the fractionated subclasses. Total amounts of IgG3 were significantly increased compared with normal controls. AMA were found in all IgG subclasses and not restricted predominantly to IgG3 as previously described. The functional affinity of IgG3 AMA is generally lower as compared with that of other subclasses. No light chain restriction was found.

Animals↗
PubMed1991

Treatment of systemic vasculitis with pooled intravenous immunoglobulin.

The therapeutic effect of a course of high-dose, pooled, intravenous immunoglobulin (IVIg) on disease activity and circulating antineutrophil cytoplasm antibodies (ANCA) was investigated in 7 patients with systemic vasculitis. 5 had active disease despite conventional immunosuppression, and 2 had not received any treatment. All 7 had clinical improvement, which was sustained in 6 and transient in 1. The fall in ANCA concentrations to a mean of 51% of the pre-treatment values was maintained during follow-up. C-reactive protein concentration also dropped considerably. IVIg seemed to confer a useful therapeutic effect without adverse reaction.

Adult↗
PubMed1991

Anti-idiotypes against anti-neutrophil cytoplasmic antigen autoantibodies in normal human polyspecific IgG for therapeutic use and in the remission sera of patients with systemic vasculitis.

Anti-neutrophil cytoplasmic antigen (ANCA) activity was inhibited in 15 out of 21 sera from patients with acute systemic vasculitis following incubation with normal polyspecific IgG for therapeutic use (IVIg). ANCA antibodies reacted with IVIg through idiotypic-anti-idiotypic interactions, as shown in competitive binding assays using F(ab')2 fragments from IVIg and affinity chromatography of ANCA IgG on Sepharose-bound F(ab')2 fragments from IVIg. Co-incubation of sera from patients with acute systemic vasculitis with paired autologous remission stage sera also resulted in inhibition of ANCA activity in acute sera. Remission sera contain IgM and IgG capable of interacting with beta and or alpha idiotypes of ANCA IgG from acute sera. Anti-idiotypic IgM may account for the lack of expression of ANCA activity in whole serum from patients in remission from systemic vasculitis, which were found to contain high titres of ANCA IgG. These observations suggest that remission of systemic vasculitis is associated with the generation of anti-idiotypes against autoantibodies rather than the suppression of production of ANCA autoantibodies. IVIg may modulate the activity of systemic vasculitis in vivo.

Antibodies, Anti-Idiotypic↗
PubMed1991

IgG subclass distribution and relative functional affinity of anti-myeloperoxidase antibodies in systemic vasculitis at presentation and during follow-up.

Circulating IgG autoantibodies to myeloperoxidase (MPO) are associated with renal vasculitis and have been implicated in its pathogenesis. However, raised levels of these autoantibodies may persist during clinical remission. We tested whether this paradox could be explained by immunoglobulin subclass switching during disease evolution, since different subclasses have different immunological and biochemical properties. Sera with anti-myeloperoxidase (anti-MPO) activity from 33 patients with active disease and 20 anti-MPO positive follow-up sera were studied by an ELISA using a panel of anti-human IgG subclass monoclonal reagents previously calibrated on human myeloma proteins. Anti-MPO subclass distribution in initial sera was: IgG1, 31 (94%); IgG2, 10 (30%); IgG3, 24 (73%); and IgG4, 22 (67%). IgG3 anti-MPO decreased during follow-up (P less than 0.02), with no change in IgG1 and IgG4. Relative functional affinity of anti-MPO antibodies in purified IgG subclasses was studied by the diethylamine method. IgG3 fractions consistently had a greater affinity for MPO than the other subclasses. Sequential studies in four patients demonstrated an affinity maturation for IgG1 and IgG4 anti-MPO as IgG3 anti-MPO disappeared. We conclude that dynamic changes of subclass distribution and affinity may explain discrepancies between anti-MPO antibody titre and disease expression.

Antibody Affinity↗
PubMed1991

IgG subclass distribution of autoantibodies to neutrophil cytoplasmic antigens in systemic vasculitis.

The IgG subclass distribution for both ANCA-specific, and total IgG subclasses, of sera from 48 patients with active systemic vasculitis was determined by solid-phase assay using monoclonal anti-human subclass reagents. To control for varying performance of the subclass reagents, the assays were calibrated with sera affinity-depleted into subclass specific fractions, whose ANCA IgG subclass distribution was determined by a common reagent. In 10 patients whose ANCA persisted during clinical remission, the ANCA IgG subclass distributions between active and remission phases of disease were compared. The total IgG subclass distribution of sera from patients with active vasculitis was similar to that found in a normal population. The ANCA IgG subclass distribution of the same sera showed relative enrichment for IgG3 and depletion of IgG2 (P less than 0.05). When the active and clinical remission ANCA IgG subclass distributions were compared, ANCA IgG3 levels had fallen and ANCA IgG2 levels were increased during remission (P less than 0.01).

Antibodies, Antinuclear↗
PubMed1990

New strategies for plasma exchange in systemic vasculitis.

The use of plasma exchange in the treatment of systemic vasculitis has been controversial and poorly defined. Since the discovery of anti-neutrophil cytoplasm antibodies (ANCA) and the demonstration of their specificity for systemic vasculitis, there has been a reassessment of the use of plasma exchange along the same lines as its use in anti-glomerular basement membrane disease. ANCA has also contributed to the diagnosis and classification of rapidly progressive glomerulonephritis, in which there is now firmer evidence to support the use of plasma exchange. Current work into the immunoregulation of ANCA by idiotype/anti-idiotype interactions is leading to new approaches to therapy and plasma exchange alone appears capable of inducing prolonged remission in some patients with vasculitis, possibly through an effect on these interactions.

Autoantibodies↗
PubMed1990

Autoantibodies to GBM and neutrophil cytoplasm in rapidly progressive glomerulonephritis.

The incidence of autoantibodies to glomerular basement membrane (AGBMA) and neutrophil cytoplasmic antigens (ANCA) in the initial sera of 889 consecutive patients with a suspected diagnosis of rapidly progressive glomerulonephritis, was determined by prospective study. Forty-seven (5%) were positive for AGBMA alone, 246 (28%) were positive for ANCA alone, 576 (65%) had neither autoantibodies while 20 (2%) had both. Clinical and pathological data collected from patients with both autoantibodies suggested the coexistence of anti-glomerular basement membrane disease and systemic vasculitis. Together, assays for AGBMA and ANCA are important in the diagnosis and management of rapidly progressive glomerulonephritis and may help its further classification.

Antibodies↗
PubMed1990

Autoantibodies to endothelial cells and neutrophil cytoplasmic antigens in systemic vasculitis.

The interaction of circulating autoantibodies with the endothelium may be an important mechanism in the pathogenesis of systemic vasculitis. In a prospective study, we looked for circulating antiendothelial cell autoantibodies (AECA) and anti-neutrophil cytoplasm autoantibodies (ANCA) in 80 patients with suspected systemic vasculitis. AECA were measured using an isotype-specific cellular ELISA incorporating human umbilical vein endothelial cells. ANCA activity was determined by indirect immunofluorescence and radioimmunoassay. Sequential studies were performed on sera from four cases with dual positivity, where autoantibody binding was compared with von Willebrand factor (vWF) concentration and disease activity. IgG AECA were significantly higher in the 27 ANCA-positive sera as compared with normal controls (P = 0.027) with IgG (P = 0.009) and IgA (P = 0.046) AECA isotypes correlating with ANCA positivity; in contrast, no differences were found between AECA levels in the ANCA-negative sera and the normal controls. Cross-inhibition studies pointed to the co-existence of two autoantibody populations. An association between autoantibody binding, disease activity and vWF concentration was found for both ANCA and AECA. Some patients with systemic vasculitis have detectable AECA that recognize different epitopes to ANCA and like ANCA, their titre correlates with disease activity and thus they may have a pathogenetic role in these conditions.

Antibody Specificity↗
PubMed1990

The specificity of anti-neutrophil cytoplasm autoantibodies in systemic vasculitides.

Autoantibodies to neutrophil cytoplasmic antigens are found in patients with small or medium-size vessel systemic vasculitis such as Wegener's granulomatosis and microscopic polyarteritis. We studied the specificity of anti-neutrophil cytoplasm autoantibodies (ANCA) by examining the binding of sera from patients with different forms of systemic vasculitis, to neutrophil extract size-fractionated by gel filtration for high performance liquid chromatography. Sequential fractions were collected for solid-phase radioimmunoassay. Patients with Wegener's granulomatosis showed two peaks of activity over fractions of 12 and 2 kD. Patients with microscopic polyarteritis had two different peaks of activity over fractions of 100 and 25 kD. Patients with Takayasu's arteritis and dermal lymphocytic vasculitis were studied as controls (all were ANCA negative by indirect immunofluorescence studies and solid-phase radioimmunoassay). However, the patient with lymphocytic vasculitis showed a distinct peak of activity over 22 kD and patients with Takayasu's arteritis had a single peak of activity over 200 kD. These results suggest the binding pattern of sera to fractionated neutrophil extract could be useful in differentiating between different diseases within the spectrum of systemic vasculitis. Cryptic antigen recognition in certain vasculitides may only be revealed by this procedure. We conclude that the association of ANCA and systemic vasculitis may not be limited to diseases of small or medium-size vessels, but could also include large vessel disease such as Takayasu's arteritis.

Antibody Specificity↗
PubMed1990

Anti-neutrophil cytoplasm antibodies in patients with monoclonal gammopathies.

Anti-neutrophil cytoplasm antibodies (ANCA) are specific markers for systemic vasculitis. In view of the autoreactivity to other autoantigens reported in patients with monoclonal immunoglobulins (MIg), the reactivity of 150 sera from 125 patients with MIg was tested for ANCA by radioimmunoassay (RIA) with inhibition stage and indirect immunofluorescence (IIF). Seven were positive for IgG ANCA, all with IgG MIg and 5 were positive for IgM ANCA, 4 with IgM MIg and 1 with IgG MIg. No IgA ANCA were found. The patterns seen on IIF were identical to those seen with sera from patients with systemic vasculitis and were cytoplasmic in 6 and peri-nuclear in 6. The restriction of the ANCA activity to the MIg was studied in six sera by light chain specific RIA, and anion exchange fractionation of the sera. The ANCA activity appeared to be polyclonal in at least three sera and could be found in the monoclonal fraction in only three patients. Associated autoimmune diseases were found in some of these ANCA positive patients including Sjögren's syndrome, MacDuffie hypocomplementemic vasculitis and rheumatoid polyarthritis but the classical vasculitic features normally associated with ANCA were not observed. We conclude that ANCA is a further autoreactivity present in some sera with MIg and discuss the relation between monoclonal gammopathies and autoimmunity.

Aged↗