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Biomedical subjects

K B Elkon

Publications and source records attributed to K B Elkon.

At least 127 records · Page 7Linked to original sources

Thrombosis in systemic lupus erythematosus: striking association with the presence of circulating lupus anticoagulant.

The lupus anticoagulant was found in the plasma of 31 of 60 patients with systemic lupus erythematosus and other connective tissue disorders (mixed connective tissue disease, systemic vasculitis, polyarteritis nodosa, primary sicca syndrome, discoid lupus, Behcet's syndrome, and systemic sclerosis). Strong associations were found with biological false positive seroreaction for syphilis and thrombocytopenia. The most striking association, however, was with the high prevalence of thrombosis. This tendency to thrombosis was independent of disease activity of systemic lupus erythematosus. The lupus anticoagulant appears to be a useful marker for a subset of patients with systemic lupus erythematosus at risk for the development of thromboembolic complications.

Adolescent↗

Induction of polymeric IgA rheumatoid factors in infective endocarditis.

IgA and IgM rheumatoid factor activity, circulating immune complex levels, and antinuclear antibodies were measured in 17 patients with subacute or chronic infective endocarditis. Approximately three fourths of these patients had both IgA and IgM rheumatoid factors detectable by radioimmunoassay, and IgA and IgM rheumatoid factor activity was strongly correlated (p less than 0.01). In three patients studied, IgA rheumatoid factor activity was predominantly polymeric as assessed by sucrose density ultracentrifugation (55 to 92 percent of total rheumatoid factor activity) and could bind radiolabeled secretory component. No correlations between rheumatoid factor activity and circulating immune complex levels or antibodies to nuclear antigens were observed. These observations indicate that circulating polymeric IgA antibodies do not necessarily signify a mucosal stimulus for IgA production and also demonstrate differences in the intensity and spectrum of autoantibody production when compared with autoimmune diseases.

Adult↗

Inhibitor of prostacyclin production in sporadic haemolytic uraemic syndrome.

Prostacyclin (PGI2) production was diminished when rat aortic rings were incubated with plasma from 5 of 6 patients with the sporadic form of haemolytic uraemic syndrome but was normal in the presence of plasma from 7 patients with the epidemic form of haemolytic uraemic syndrome or from patients with other renal diseases. The reduced PGI2 production was caused by an unstable inhibitor, extractable into polar lipid solvents, in sporadic haemolytic uraemic plasma. These results suggest that there may be at least 2 different pathogenetic mechanisms in epidemic and sporadic haemolytic uraemic syndrome and that the reduced PGI2 production observed in the sporadic type is due to an inhibitor of PGI2 production rather than a deficiency of stimulating factors.

Adolescent↗

Pulmonary involvement in angioimmunoblastic lymphadenopathy following autoimmune disease.

A 44-year-old woman presented with a systemic illness characterized by a rash, polyarthritis and hypothyroidism. She later developed angioimmunoblastic lymphadenopathy (AIL) which became progressively resistant to chemotherapy. Pulmonary features were prominent throughout her illness and included pleural effusions, hilar adenopathy and parenchymal infiltrates. Lung histology showed a transition from nonspecific chronic inflammation with fibrosis to a polymorphic cellular infiltrate typical of AIL. Immunological features included a low C3 level, hypogammaglobulinaemia and depressed cell-mediated immunity.

Adult↗

IgA and IgM rheumatoid factors in serum, saliva and other secretions: relationship to immunoglobulin ratios in systemic sicca syndrome and rheumatoid arthritis.

Paired serum and saliva samples from seven patients with systemic sicca syndrome (SSS), 15 patients with rheumatoid arthritis and a positive Schirmer's test (RA+), 15 patients with rheumatoid arthritis and negative Schirmer's test (RA-) and 14 normal individuals were analysed for albumin and immunoglobulin concentration as well as IgA and IgM rheumatoid factor (RF) activity. Protein levels in saliva were higher in SSS and RA+ but, when corrected for serum concentration and salivary flow rate, only the IgG ratio remained significantly elevated in SSS (P less than 0.01) and RA- (P less than 0.05) and the IgM ratio was reduced in RA- (P less than 0.05) compared to controls. Although IgM RF activity in serum and saliva was strongly correlated (P less than 0.001) in all three patient groups, the activity in saliva was considerably lower than serum activity. In the two (RA) patients tested, IgM RF in saliva contained secretory component. Mean salivary IgA RF activity varied between 34% (RA-) and 84% (SSS) of serum activity and correlated with serum activity in SSS (P less than 0.001) and RA- (P less than 0.01). IgA RFs in saliva, but not in serum, contained secretory component. Additional demonstration of IgA RF activity in nasal and duodenal secretions in SSS may be related to involvement of the common mucosal immune system.

Adult↗

Evaluation of heat-damaged and IgG-coated red cells for testing reticuloendothelial function.

In vitro methods for standardising and assessing the reproducibility of reticuloendothelial function tests in man were performed. Variation in the degree of heat-induced red blood cell damage could be detected by both Channelyzer plots and a filtration test of red cell plasticity although the former test was less sensitive and difficult to quantitate. In a consecutive study of the clearance of heat-damaged red blood cells (HDRBC) in 8 patients and 2 normal individuals, consistent changes were demonstrated by both assays although occasionally one assay alone provided inconclusive results. When undamaged red cells were coated with IgG anti-D antibodies, the number of IgG molecules bound per red cell was determined by an indirect antiglobulin radioimmunoassay. With this assay, it was shown that the rate of clearance of coated cells was related to the amount of cell bound IgG anti-D. Some variation in the degree of coating of cells from patients with systemic lupus erythematosus was found although the differences were insufficient to account for the reported reduction in the clearance of IgG-coated cells in patients with this disease. The radioimmunoassay and microhaemagglutination techniques revealed that neither IgG, Clq, C3 or C3d were bound to HDRBC following incubation in autologous serum suggesting that these cells were cleared in vivo by mechanisms unrelated to immune receptor recognition.

Antibodies, Anti-Idiotypic↗

Adult-onset Still's disease. Twenty-year followup and further studies of patients with active disease.

Eleven female patients with adult-onset Still's disease were followed for 7-36 years (mean 20.2 years) after the onset of their illness. Ten of these patients had a chronic course characterized by remissions and exacerbations of arthritis associated with fever and rash. Five patients had terminal interphalangeal involvement, and carpal ankylosis was demonstrated on x-ray film in 10. Two patients developed a widespread polyarthritis, and renal amyloidosis was diagnosed 10 years after disease onset in the most severely affected patient. In 4 patients studied during an exacerbation of the disease, circulating immune complexes were detected by the staphylococcal A binding assay, but not by the C1q binding assay. Synovial fluid analysis in 1 patient revealed a low C3 level and total hemolytic complement (CH50) together with immune complexes and IgG rheumatoid factor. Immune complexes were not identified in the characteristic Still's rash by immunofluorescence or electron microscopy, although mast cell degranulation, neutrophil lysis, and perivascular fibrin deposition were reminiscent of immune complex--mediated vascular injury. The clinical and laboratory features as well as the long-term course of adult- and juvenile-onset systemic Still's disease are similar, but further studies of genetic markers and immunopathology are required to establish a common pathophysiology.

Adult↗

Kinetics of heat damaged autologous red blood cells. Mechanism of clearance from blood.

The kinetics of radiolabelled heat damaged red cell (HDRBC) distribution have been studied in humans using a gamma camera, and compared with the kinetics of other blood cells. Liver uptake of 111In labelled HDRBC was completed within about 10 min of injection; splenic uptake was biphasic with a half time of about 5 min over the first 20 min following injection, and a later half time much longer than this. Activity initially present in the lung fields cleared within 24 h. The rate constants of liver uptake of 99mTc labelled HDRBC and of 111In labelled platelets were very similar; the rate constants of splenic uptake of these 2 particles were also very similar up to about 20 min following injection when the splenic platelet levels became constant and the HDRBC level continued to slowly rise. Splenic uptake and blood clearance of red cells coated with IgG (IgG-RBC), in contrast to HDRBC, were monoexponential. It was concluded that: (1) the blood clearance of HDRBC was due to pooling within, and to irreversible extraction by, the spleen; (2) liver uptake of HDRBC, which was irreversible, was completed within 10 min of injection; (3) IgG-RBC clearance was due to irreversible extraction by the spleen; (4) HDRBC uptake in the lung was unrelated to reticuloendothelial function, and represented prolonged transit through the lung microvasculature.

Blood Platelets↗

Systemic inflammatory complications following jejuno-ileal bypass.

The clinical and laboratory features of three patients with systemic inflammatory complications following jejuno-ileal bypass surgery for morbid obesity are described. The constellation of an asymmetrical polyarthritis, tenosynovitis, sterile skin pustules, mucous membrane ulceration and retinal vasculitis resembled Behçet's syndrome. Serum complement levels were normal and circulating immune complexes not regularly detected, although hypocomplementaemia, elevations in Clq and rheumatoid factor binding materials were noted prior to clinical relapse in one patient. Antibiotic therapy proved disappointing, whereas dapsone produced a sustained remission. Bacterial overgrowth was not invariably found which together with recurrence of symptoms following bypass reversal, suggest that bacteria may only be required to initiate, not perpetuate inflammatory complications.

Arthritis↗

Analysis of heat-damaged erythrocyte clearance curves.

The rate of clearance from the blood of heat-damaged erythrocytes (HDE) is used routinely as a quantitative assessment of splenic function. The time taken for the value at 3 min to fall by 50% (t0.5)is usually taken as the index of function. The clearance of HDE is dependent on three processes: splenic blood flow, splenic HDE extraction ratio and intrasplenic transit time of "unextracted' HDE, returning to the circulation. Exponential analysis of the clearance curve can resolve these three functions. Simple methods of analysis, however, such as t0.5, which are applied directly to the curve, may be weighted in favour of any one of them. In this paper, a large number of clearance curves have been analysed and the components of splenic function resolved. The t0.5, the percentage fall in HDE between 8 and 28 min (C20), the rate constant at 8 min (K8) and the rate constant of the tail of the curve (alpha 2) have been correlated with these components. K8 showed a close correlation with splenic blood flow, and alpha 2 with the rate of HDE phagocytosis. In general, the correlation between the various components of splenic function was better with C20 than with t0.5. This is explained predominantly by the fact that the t0.5 includes liver clearance. The t0.5 should therefore be used with caution as an estimate of splenic function, which can be usefully assessed by applying alternative simple methods of analysis described.

Erythrocytes↗

Measurement of splenic function in humans using heat damaged autologous red blood cells.

Functional hyposplenism, a clinical entity which has only recently been recognised, is usually assessed quantitatively by the rate of clearance of radiolabelled heat damaged erythrocytes (HDE) from the circulation. Based on recent observations on the kinetics of HDE, we have developed a 3 compartmental model of HDE distribution between the spleen and blood, and calculated, in a large series of clearance curves, splenic blood flow, HDE intrasplenic transit time and splenic HDE extraction ratio. Transit time (about 15 min) was of the same order as platelet transit time and extraction ratio (about 35%) was similar to that recorded in animals. Thr relationships between blood flow, transit time and extraction ratio provided evidence in support of 2 separate functional compartments, of which only one was engaged in phagocytosis, present within the spleen.

Erythrocytes↗

The effect of a protein meal on three fluid-phase assays for circulating immune complexes.

Serial blood samples were taken from eight patients with systemic lupus erythematosus and five normal controls before and after a standard meal containing 20 g of protein. The samples were assayed for circulating immune complexes by the fluid-phase C1q, monoclonal rheumatoid factor and conglutinin-binding assays. No significant differences were seen in the post- as compared to the pre-prandial levels of circulating immune complexes. In neither controls nor patients did circulating complexes appear for the first time within 90 min after starting the meal. We conclude that if systemic antigen--antibody reactions occur soon after a protein meal they are not detected by the polyethylene glycol-dependent tests in current use and do not appear to influence the immediate clearance of endogenous immune complexes.

Antigen-Antibody Complex↗

Radioimmunoassay profile of antiglobulins in connective tissue diseases: elevated level of IgA antiglobulin in systemic sicca syndrome.

A microplate radioimmunoassay for IgG, IgA and IgM antiglobulins reactive with rabbit IgG was performed on sera from 69 patients with various connective tissue diseases. IgM antiglobulins were detected in rheumatoid arthritis, systemic sicca syndrome and some patients with systemic vasculitis. IgA antiglobulins were found in seven of 10 patients with systemic sicca syndrome and only five of 59 patients with other connective tissue diseases. There was no correlation between the levels of IgM and IgA antiglobulins in the systemic sicca syndrome or rheumatoid arthritis (r = -0.21 and 0.2 respectively). IgG antiglobulins were not detected in any serum which lacked IgM or IgA antiglobulins. IgG isolated by DEAE columns showed antiglobulin activity in six of 15 rheumatoid arthritis and two of 10 systemic sicca syndrome sera tested. Antiglobulin analysis of sera fractionated by sucrose density ultracentrifugation at neutral and acid pH enabled the size of each class of antiglobulin to be determined. In certain sera, antiglobulin activity extended into the denser region of the gradient at pH 7.2 suggesting that the antiglobulins were complexed.

Adult↗

Complement fixing properties of antibodies to double-stranded DNA in systemic lupus erythematosus.

Anti-DNA antibodies were assessed in 33 patients with active systemic lupus erythematosus (SLE) by the immunofluorescence Crithidia luciliae (CL) and the Farr assays. Eleven patients demonstrated complement (C3) fixation in the CL assay. Although 6 out of 9 patients with active nephritis showed complement fixation, 6 patients without overt renal disease were also positive in this assay. The ability to fix C3 was strongly associated with the total amount of anti-DNA antibodies as determined by both the CL and Farr assays (P less than 0.001). IgM anti-DNA antibodies were detected only in sera with complement fixing anti-DNA antibodies. Isolated whole IgG, but not the F(ab')2 fragment containing anti-DNA activity, fixed C3 on the Crithidia substrate. In depletion and reconstitution studies with human complement components, it was established that anti-DNA antibodies fixed C3 through the classical complement pathway although factors B and D of the alternative pathway were effective in C3 amplification. Properdin was also detected on the antigen-antibody complex but did not appear to be essential for maximal C3 fixation. Anti-DNA antibodies therefore fix complement by their Fc portion, form a classical pathway convertase, and recruit factors B and D of the C3b amplification loop when they bind to a fixed antigen.

Antibodies↗