Biomedical subjects

M E Devey

Publications and source records attributed to M E Devey.

At least 37 records · Page 2Linked to original sources

PubMed1988

Serial studies of the IgG subclass and functional affinity of DNA antibodies in systemic lupus erythematosus.

The functional affinity and IgG subclass of antibodies to ss and dsDNA were measured by ELISA in five serial samples from 41 patients with systemic lupus erythematosus (SLE) who were divided into relatively homogeneous disease subgroups. Anti-dsDNA antibodies were restricted to IgG1 and IgG3 in renal disease and levels increased with disease severity. Functional affinity of IgG1 and IgG3 anti-dsDNA fell in patients with severe renal disease, suggesting that the high affinity antibody population lost from the serum was localizing in the kidneys. IgG2 anti-dsDNA were found in patients with joint and skin disease alone and in the thrombotic/spontaneous abortion subgroup. IgG2 antibody levels did not correlate with disease severity but did correlate with the presence of antibodies to Klebsiella K30 and may have represented a cross-reactive antibody population.

Antibodies, Antinuclear↗

PubMed1988

Functional affinity of IgM rheumatoid factor in patients with rheumatoid arthritis and other autoimmune diseases.

The functional affinity of IgM rheumatoid factors (RF) was measured in 31 patients with rheumatoid arthritis (RA), 24 with systemic lupus erythematosus (SLE), 13 with Sjögren's syndrome (SS), and in 13 seropositive healthy individuals. The functional affinity of IgM RF from patients with RA was significantly lower than in the other clinical groups studied. In addition, there was a significant inverse correlation between functional affinity and titre of IgM RF in all the groups. These results suggest that the usual mechanisms of affinity based selective pressure (somatic diversification and antigen selection) may operate differently for autoantibodies to serum antigens such as IgG.

Antibody Affinity↗

PubMed1988

IgG subclass composition of antibodies to HBsAg in circulating immune complexes from patients with hepatitis B virus infections.

The IgG subclass of antibody associated with hepatitis B surface antigen (HBsAg) in circulating immune complexes (CIC) from patients with either acute or chronic hepatitis B virus (HBV) infections was measured using an isotype and antigen-specific ELISA. All patients were HBsAg positive but were negative for free anti-HBs antibody. The subclass of antibody associated with HBsAg in CIC in both groups was predominantly IgG1 and IgG4. This is in contrast to free anti-HBs in convalescent sera from patients recovering from HBV infection, which are highly restricted to IgG1 and IgG3. The finding of high levels of IgG4 antibodies in CIC suggest that CIC containing this subclass may be cleared less efficiently than CIC containing antibodies of other subclasses. Formation of these CIC may be an important factor in the progression of infection to chronicity and may also be involved in the antigen-specific immunosuppression seen in early acute and chronic HBV infections.

Acute Disease↗

PubMed1987

The effect of rheumatoid factor on the clearance of endogenous immune complexes formed in low-affinity mice during the induction of immune complex disease.

Intravenous injection of rheumatoid factor (RF) had a marked effect on the clearance kinetics of immune complexes (IC) formed in vivo during induction of chronic immune complex disease in low-affinity mice. RF resulted in a significant increase in IC level and clearance time in 64% of mice with circulating IC after antigen injection, suggesting that RF may alter the handling of potentially pathogenic IC which localize in the renal capillaries causing glomerulonephritis.

Animals↗

PubMed1987

Antibody affinity and IgG subclass of responses to tetanus toxoid in patients with rheumatoid arthritis and systemic lupus erythematosus.

Significant differences in both the affinity and IgG subclass of antibodies produced after immunization with tetanus toxoid have been demonstrated in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) compared to healthy controls. Patients with RA failed to show affinity maturation although they produced similar amounts of antibody to the controls. Some patients with SLE produced very high affinity antibodies although there was a wide spectrum of response. Antibodies to tetanus toxoid in controls were predominantly IgG1 and IgG4 but in RA and SLE there was either a restricted IgG1 response or a more general response in all the IgG subclasses. It is likely that these differences in response reflect the underlying disorders in immunoregulation present in patients with these diseases.

Adult↗

PubMed1986

Studies on rheumatoid factor: I. The effect of rheumatoid factor on the clearance of preformed immune complexes in mice.

The blood clearance of passively transferred immune complexes (IC), preformed at different antigen-antibody ratios, was measured in mice with LPS-induced rheumatoid factor (RF) and in normal controls. RF had a differential effect on IC clearance, significantly enhancing clearance of complexes formed in antibody excess and slight antigen excess but inhibiting the clearance of complexes formed in moderate (x10) antigen excess. The results are discussed with regard to the mechanisms of IC clearance and suggest that RF may play an important role in governing the behaviour of immune complexes in vivo.

Animals↗

PubMed1985

The IgG4 subclass is associated with a low affinity antibody response to tetanus toxoid in man.

The amount and relative affinity of antibodies to tetanus toxoid were measured, following immunization, in patients with chronic or recurrent acute chest infections and in healthy controls. The responding patients and controls produced similar amounts of antibody and, although antibody affinity was higher in the controls compared to the patients, the differences were not significant. Most individuals (65%) produced antibody of the IgG1 subclass with little or no IgG4 antibody, but in the remainder antibody was either predominantly IgG4 (29%) or equally distributed between the IgG1 and IgG4 subclasses (6%). Antibody affinity was significantly lower in both patients and controls producing IgG4 antibodies compared to those with a predominantly IgG1 response, and antibody affinity increased with the amount of IgG1 antibody present. These results provide preliminary evidence of an association between low antibody affinity and the IgG4 subclass in man.

Acute Disease↗

PubMed1984

Failure of affinity maturation leads to increased susceptibility to immune complex glomerulonephritis.

Mice, previously selected for the production of low affinity antibody after four injections of protein antigens in saline, fell into two groups on the basis of their antibody response after injection of adjuvantized antigen. One group produced antibody of sequentially rising affinity but the other produced only low affinity antibody. Mice from the latter group were interbred to produce low affinity non-maturing mice (low N/M mice). Daily injections in these mice produced a more rapid and severe glomerulonephritis than that observed in mice of the original low affinity line. Male low N/M mice were more severely affected than female low N/M mice. Susceptibility to the disease were associated not only with an inability to produce the maturational transition from low affinity to high affinity antibody with time but also with the production of low levels of antibody. It is suggested that these quantitative and qualitative defects in the antibody response may lead to increased susceptibility to immune complex disease.

Animals↗

PubMed1984

Antigen feeding modifies the course of antigen-induced immune complex disease.

Low affinity mice, prone to chronic immune complex disease (ICD) induced by daily injection of antigen, were fed 0.05% HSA in their drinking water for 7 days before the start of daily injections of HSA. Antigen feeding resulted in a marked decrease in the incidence of ICD despite the presence of high levels of circulating immune complexes. These complexes, which persisted in the circulation for long periods, were of low molecular weight and did not localize in the glomeruli. Antigen fed mice had lower levels of free antibody in their sera compared with control mice which may have favoured the formation of small latticed complexes in antigen excess. Antibody affinity was not apparently affected by prior feeding with antigen.

Administration, Oral↗

PubMed1982

Immunoglobulin class and subclass distribution of dextran-reactive antibodies in human reactors and non reactors to clinical dextran.

The red cell-linked antigen-antiglobulin reaction (RCLAAR) with stearoyldextran-coated erythrocytes was used to characterize the immunoglobulin (Ig) classes and IgG subclasses of dextran reactive antibodies (DRA) in 27 dextran reactors (DR) and 96 on reactors (DNR). High titres of dextran reactive IgG were regularly found in sera of patients with severe dextran-induced anaphylactoid/anaphylactic reactions (DIAR) prior to the infusion. In four lethal cases IgG antibodies were found to be in the highest titre range of 16,384 to 32,768. In addition, high IgA and IgM titres were also in severe DIAR. DNR had much lower titres of dextran reactive antibodies of IgG, IgM and IgA classes and IgD antibody was absent in both groups. Dextran reactive IgE antibodies were not demonstrable in DR. Dextran reactive IgG2, IgG3, IgG4 and IgG1 (indirect measurement) were demonstrated in both DR and FNR. Dextran infusion caused variable neutralization in all Ig classes and IgG subclasses, but the contribution of IgG2 was considered most important because of its high titres and most pronounced neutralization in severe DIAR. It is concluded that DRA mainly of the IgG class, play a critical pathogenic role in the induction of severe DIAR, which accordingly is classified as immune complex (Type III) anaphylaxis. The method of RCLAAR allows to delineate a risk group of about 2% of potential reactors.

Adolescent↗

PubMed1982

Experimental antigen-antibody complex disease in mice. The role of antibody levels, antibody affinity and circulating antigen-antibody complexes.

Chronic antigen-antibody complex disease (A-ACD) was induced in mice by daily injections of HSA. The disease was characterized by death, intense glomerular basement membrane deposition of complexes in the kidneys, proteinuria and an impairment of the glomerular filtration rate. In mice that had been selectively bred to produce antibody of low affinity to protein antigens injected in saline, the incidence of chronic A-ACD was 61% compared to 21% in mice selectively bred to produce antibody of high affinity. Low affinity female mice produced approximately ten times as much free antibody to HSA as did low affinity males and high affinity males and females, but this did not result in an increase incidence of chronic A-ACD in low affinity female mice. Low affinity female mice also had the highest levels of circulating antigen-antibody complexes detected by conglutinin and Clq binding assays, but there was no correlation between the presence of high levels of complexes in serum and tissue damage. In both lines of mice the mean affinity of free antibody to HSA started low and increased with time and the number of injections of antigen. However, development of chronic A-ACD in individual low affinity mice appeared to be associated with a failure to produce this time-associated increase in antibody affinity. These results are discussed with reference to the relevance of the measurement of the amount of affinity of free antibody in serum and the levels of circulating antigen-antibody complexes to the production of tissue damage in this model of chronic A-ACD.

Animals↗

PubMed1981

Chronic antigen-antibody-complex glomerulonephritis in mice.

Daily injection of human serum albumin into mice genetically selected to produce low-affinity antibody to protein antigens resulted in a more severe antigen-antibody-complex-induced glomerulonephritis than in mice producing high-affinity antibody. The low-affinity mice had higher levels of circulating antigen-antibody complexes, greater impairment of renal function and reduced reticuloendothelial clearance of 125I-PVP compared to high-affinity mice. Electron microscopy of glomeruli revealed the presence of subepithelial electron-dense deposits in low-affinity mice and predominantly subendothelial-mesangial deposits in high-affinity mice which corresponded to the predominantly capillary staining in low-affinity mice and mesangial staining in high-affinity mice by immunofluorescence. Auto-radiography of electron-microscopy sections demonstrated the presence of antigen in the electron-dense deposits, indicating that these deposits indeed contained antigen-antigen complexes.

Animals↗

PubMed1980

Measurement of antigen-antibody complexes in mouse sera by conglutinin, C1q and rheumatoid factor solid phase binding assays.

The application of three solid phase tests for the detection of antigen-antibody complexes in the sera of inbred and selectively-bred mice with experimentally induced chronic antigen-antibody complex disease is described. Two of the tests used--the C1q binding assay (C1qBA) and the conglutinin binding assay (KBA)--were previously described methods which we have modified for the detection of murine complexes. The third test is a new solid phase polyclonal rheumatoid factor binding assay (RFBA). The results demonstrate that the correlation of positivity with the three methods varied during the course of a chronic disease but in general results with the KBA showed a better correlation with the RFBA than with the C1qBA. Furthermore, the KBA and RFBA preferentially bound complexes of lower molecular weight than did the C1qBA. It is suggested that the parallel use of these three tests during the study of murine antigen-antibody complex disease will provide valuable information concerning the nature of the complexes involved; since the three tests, when run in parallel, will detect large complement fixing complexes (C1q), small complement fixing complexes (KBA) and small non-complement fixing complexes (RFBA).

Animals↗

PubMed1980

The induction of chronic antigen-antibody complex disease in selectively bred mice producing either high or low affinity antibody to protein antigens.

Mice selectively bred to produce either high or low affinity antibody to protein antigens were injected daily with bovine serum albumin (BSA) and studied for the development of chronic antigen-antibody complex disease. After 41-44 injections of BSA, evidence of circulating antigen-antibody complexes and renal localization of complexes was obtained in both lines. However, low affinity mice had significantly higher levels of circulating complexes than high affinity mice. Impairment of renal function was seen in low affinity mice but not in high affinity mice and there was significantly more complex deposition in the glomeruli of low compared to high affinity mice. Furthermore, the pattern of localization of complexes was predominantly mesangial in high affinity mice but in low affinity mice the deposition was both mesangial and in the glomerular basement membrane. The role of antibody affinity in the induction of chronic antigen-antibody complex disease is discussed in the light of these results.

Animals↗

PubMed1979

Anaphylactic sensitivity of guinea-pigs drinking different preparations of cows' milk and infant formulae.

Guinea-pigs have been given various preparations of cows' milk or infant formulae to drink in an investigation of the capacity of these milk preparations to stimulate per os anaphylactic sensitivity. The treatment, presumably heat, used to concentrate the 'Evaporated' whole cows' milks (three brands were tested) almost abolished their sensitizing capacity to beta lactoglobulin. The brand presumed to be most heated as judged by the degree of caramelization had also lost most of its sensitizing capacity to casein. Injected parenterally, the 'Evaporated' milk adequately sensitized to anaphylaxis. An infant formula, which in its spray dried form was only moderately sensitizing to both beta lactoglobulin and casein, lost most of this sensitizing capacity when processed to a liquid concentrate state. The manufacturing process for the liquid concentrate involved greater and more prolonged heating than required for the spray-dried form. The relevance of these findings in the guinea-pig to cows' milk protein intolerance in the infant and possibly also to cot death is discussed.

Anaphylaxis↗

PubMed1978

Refractoriness to anaphylactic shock after continuous feeding of cow's milk to guinea-pigs.

Further studies have been undertaken on the anaphylactic sensitization to cows' milk in guinea-pigs given cows' milk to drink instead of water. With continuous feeding over a prolonged period of time (over 70 days), about 70% of the guinea-pigs became refractory to intratracheal challenge of cows' milk and about 30% to intravenous challenge. Some guinea-pigs given cows' milk from the second day of life appeared not to undergo an early sensitization at all and may have been displaying a tolerance to anaphylactic sensitization. The degree to which this was shown may be genetic. The anaphylactic sensitivity, particularly as regards intravenous challenge, could be assessed by examining the sera for IgGl a antibodies to cows' milk by passive cutaneous anaphylaxis.

Anaphylaxis↗

PubMed1976

The IgG subclasses of antibodies to grass pollen allergens produced in hay fever patients during hyposensitization.

Total IgG, IgG subclass and IgE antibodies specific for grass pollen allergens were measured by the red cell linked antigen-antiglobulin reaction (RCLAAR) in a serum samples from nineteen patients who had undergone a course of hyposensitization. Increases in both specific IgG and IgE antibodies were seen after treatment in most patients. In the IgG subclasses the predominant response was for IgG1 and IgG4 antibodies. Attempts were made to correlate the antibody responses with the clinical response and the results are discussed with reference to the possible mechanisms of hyposensitization.

Antigen-Antibody Reactions↗

PubMed1976

Penicillin allergy studies by a modified red-cell-linked antigen-antiblobulin reaction.

A red-cell-linked antigen-radioactive antiglobulin reaction (RCLA AR) is reported which may be combined with the conventional red-cell-linked antigen-antiglobulin reaction (RCLAAR) to measure antibodies of all five immunoglobulin calsses against the same determinant at the same time. The method has been applied to sera from penicillin-allergic patients and controls. Human erythrocytes coated with rabbit antibodies carrying penicilloyl groups were incubated with the serum to be tested, then washed. 125I-labelled anti-human IgE was added and, after further incubation and washing, the radioactivity retained by the cells was counted. This gives a measure of the specific IgE in the test sample. Other aliquots of the coated cells were treated with specific antiglobulin reagents in the usual manner of the RCLAAR in order to determine antibodies of other classes. The sensitivity for IgE was similar to that of the radioallergosorbent test. Information was also obtained about specific IgG subclasses.

Animals↗