Galactosylation of IgG associated oligosaccharides.
Explore the source record for details and available documents.
Galactose↗
Biomedical subjects
F C Hay
Publications and source records attributed to F C Hay.
Rheumatoid factor: structural and genetic studies indicating novel binding sites may confer the specificity for IgG Fc.
Comparison of sequences of mouse rheumatoid factor light chains has previously suggested that the sites for rheumatoid factor activity lie outside the conventional hypervariable regions which normally bind antigen and, instead, may be related to the light chain variable region framework sequences. Comparison with amino acid sequences of human rheumatoid factors reveals that similar sequences are present in the variable region frameworks of these antibodies as well. It is therefore proposed that novel binding sites may be present in these framework regions which confer a structural specificity for binding IgG Fc.
Amino Acid Sequence↗
Recognition of several idiotopes on a monoclonal anti-hepatitis B virus surface antigen using monoclonal anti-idiotypic antibodies.
A monoclonal murine antibody H3F5 directed to the a determinant of hepatitis B surface antigen (HBsAg) was used to raise several monoclonal anti-idiotypes. Cross-blocking experiments between the anti-idiotypes and the patterns of inhibition produced by a number of other monoclonal anti-HBsAg, generated in the same fusion as H3F5, identified three idiotopes on H3F5 which were shared to varying degrees with the other anti-HBsAg monoclonals. One behaved as a dominant cross-reacting idiotope (CRI) in that it appeared strongly in 5/7 monoclonal idiotypes. The CRI could represent an important target for regulation by anti-idiotope. Monoclonal antibodies have many advantages over polyclonal sera in the detailed analysis of idiotope structures.
Animals↗
The relationship between induced and spontaneous autoantibodies in MRL mice: the role of Ly-1 B cells?
The murine response to bromelain-treated mouse red blood cells (BrMRBC) is derived from Ly-1 B cells. It has been proposed that this B-cell subset produces a variety of other autoantibodies and is elevated in autoimmune mouse strains. We have studied the ability of MRL lpr/lpr and the non-autoimmune congenic MRL +/+ mice to make autoantibodies to BrMRBC and immunoglobulin (rheumatoid factors, RF). Following lipopolysaccharide (LPS) stimulation we found the numbers of autologous plaque-forming cells (PFC) to be low in both lpr and MRL +/+ mice, suggesting low Ly-1 B-cell numbers. This observation is consistent with the view that Ly-1 B cells in the mouse may not give rise to pathologically relevant RF.
Animals↗
Heterogeneity in rheumatoid factor isotypes and specificities in MRL mice.
MRL/lpr mice spontaneously develop an arthritis which, in several respects, is similar to human rheumatoid arthritis, including joint inflammation and circulating rheumatoid factors. In human disease, circulating IgM rheumatoid factor (RF) predominates but, surprisingly, in these mice we have detected much more IgA rheumatoid factor. This IgA rheumatoid factor has a major specificity for IgG2a, but heterogeneity in binding specificity was seen between different mice. IgG rheumatoid factors were determined in a heterologous mouse IgG assay, in which each subclass of rheumatoid factor was tested for its ability to bind to the remaining IgG subclasses. Rheumatoid factor activity was detected in all the IgG subclasses, but particularly elevated levels were seen in IgG3 and IgG1. Both the levels and specificities of IgG rheumatoid factors were markedly different between each mouse.
Animals↗
Reduced B-cell galactosyltransferase activity in rheumatoid arthritis.
Autosensitisation to IgG may be important in the pathogenesis of rheumatoid arthritis and could be related to reduced glycosylation of the oligosaccharides in the C gamma 2 region of serum IgG. The activity of galactosyltransferase, the enzyme that catalyses the addition of galactose to the oligosaccharide chains, was measured in the circulating B cells of seventeen patients with classic rheumatoid arthritis. It was significantly lower than that of a group of eleven controls (p less than 0.001) or of nine age-matched controls (p less than 0.001). In contrast, the enzyme activity of the T cells was within the range of that in nine age-matched controls, and enzyme activity in monocyte-rich mononuclear-cell populations was higher than in controls, possibly reflecting stimulation of the monocytes in rheumatoid arthritis. These findings suggest that galactosyltransferase may regulate the degree of glycosylation during IgG synthesis and could therefore be implicated in the rheumatoid inflammatory process.
Adult↗
Characterization of sperm antigens reacting with human antisperm antibodies.
Antibodies reacting with human spermatozoa have been detected by various immunological techniques in the sera of subfertile men. Different patterns of sperm agglutination are observed with different sera, either head-to-head, tail-to-tail, or tail-tip-to-tail-tip. Differences have been detected between the clinically relevant antibodies in spontaneously infertile males and the less important antibodies in males who have undergone reversal of vasectomy. It has been suggested that the variations in agglutination patterns are due either to different classes of antibody or to binding of antibody to different antigens. In the present study immunoblotting techniques were used to characterize the reactivity of solubilized sperm proteins with serum samples exhibiting different modes of sperm agglutination. This involved the electrophoretic transfer of proteins from SDS gels to nitrocellulose sheets followed by overlay with serum antibody. Using these techniques we have attempted to characterize the antigens of spermatozoa which react with sera from both spontaneously infertile and vasovasostomized men. The results showed that although antisperm antibodies bind to discrete and sperm-associated antigens, there is no substantial difference between the antigenic patterns observed with antibodies producing different types of sperm agglutination. Neither the antigens detected, nor the intensity of reaction showed significant differences although there was a tendency for head-to-head agglutinating antibodies to react more strongly with the higher molecular weight antigens. Moreover, although with sequential serum samples the patterns of agglutination may change, the antigenic pattern remains unchanged.
Autoantibodies↗
Immunofluorescent technique for the detection of monoclonal internal image anti-idiotypic antibodies of hepatitis B surface antigen.
Monoclonal anti-idiotypic antibodies to HBsAg were screened by immunofluorescence for the presence of a subset behaving as the internal image of the original antigen. We describe the technique and the criteria fulfilled to establish that 2/6 monoclonals studied act as the internal images of the a determinant of hepatitis B surface antigen.
Animals↗
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↗
Monoclonal 'internal image' anti-idiotypic antibodies of hepatitis B surface antigen.
The hypervariable regions of the immunoglobulin molecule which function as the antigen-combining site are, themselves, capable of provoking an antibody response. These antigenic determinants on the immunoglobulin are termed the 'idiotype', and antibodies directed against them 'anti-idiotype'. In circumstances where there is a close complementarity of shape between antigen and idiotype, and subsequently between idiotype and anti-idiotype, it would be predicted that anti-idiotype would be like an 'internal image' of the antigen. Starting with a monoclonal antibody (idiotype) to the protective a determinant of the hepatitis B surface antigen (HBsAg), we have succeeded in raising two monoclonal anti-idiotypes which mimic HBsAg in their ability to bind polyclonal antibodies to HBsAg produced in a variety of species. These internal image anti-idiotypes may provide a strategy for immunization without the need for antigen.
Animals↗
The isotype and specificity of antiglobulins in BALB/c mice.
Antiglobulin activity was detected in the IgM class and the IgG1, IgG2a and IgG2b subclasses in normal and unstimulated BALB/c mice. There was an age related increase in their IgM antiglobulin, but this increase was not observed with IgG antiglobulin. Antiglobulin production could be induced by polyclonal activation of BALB/c mice with lipopolysaccharide, but this produces an increase in IgM antiglobulin only. IgM antiglobulin binding with mouse IgG1 and human IgG peaked on day 4 following lipopolysaccharide, whereas IgM antiglobulin binding with mouse IgG2a peaked around day 7. There was no IgM response with specificity for binding to mouse IgG2b. The level of IgG antiglobulin remained constant following polyclonal activation of BALB/c mice with lipopolysaccharide. Interestingly IgG antiglobulin binds preferentially with isologous IgG compared with heterologous IgG. Possible physiological roles have been discussed for the presence of these rheumatoid factors in normal mice.
Aging↗
Association of HLA-DR4/Dw4 and DR2/Dw2 with radiologic changes in a prospective study of patients with rheumatoid arthritis. Preferential relationship with HLA-Dw rather than HLA-DR specificities.
Patients admitted to a prospective study within a year of onset of suspected rheumatoid arthritis showed a positive correlation between HLA-Dw4 and the eventual severity of peripheral radiologic changes. Dw4 and DR4 were strongly associated with severity of erosions when analysis was restricted to each of the following: patients with erosions, those under 50 at onset, and all females. Relationships were consistently stronger with Dw4 than with DR4. Another D-related specificity, MT3, was positively correlated and Dw2/DR2 negatively correlated with erosions.
Age Factors↗
Elastase activity in serum and synovial fluid of patients with connective tissue disorders.
Sera and synovial fluids (SF) from patients with connective tissue disorders had significantly lower levels of elastase than sera from healthy controls. Patients with rheumatoid arthritis had significantly lower elastase activity in SF compared with serum. Elastase activity in serial serum samples from patients with systemic lupus erythematosus undergoing plasmapheresis showed some relationship with the clinical condition but little correlation with levels of circulating immune complexes. It was concluded that free elastase in the serum or SF was unlikely to be of much pathological significance in connective tissue disease.
Adult↗
A comparative study of complement components in polyethylene glycol precipitated immune complexes from patients with ovarian cancer and patients with rheumatoid arthritis.
Circulating immune complexes and complement components C1q, C3 and C4 were measured following polyethylene glycol precipitation of serum from patients with ovarian cancer (OC), patients with rheumatoid arthritis (RA) and control patients (CP). The C3 and C4 content of the precipitated material was significantly greater in those patients with OC in comparison to those with RA or CP, while the C1q content did not differ significantly between the two groups of patients. A statistically significant correlation between IgG, C3 and C4 levels was found in the immune complexes of both groups of patients. C1q levels correlated significantly with IgG immune complex levels in patients with RA and CP, but did not in patients with OC. These data illustrate that immune complexes from patients with OC differ from complexes precipitated from RA sera and normal sera in their complement content. It is suggested that the largely unsuccessful attempts to detect immune complexes in sera from patients with ovarian cancer, using assays dependent on the binding of C1q may be related to differences in solubility of complexes from these patients in comparison to complexes present in non-neoplastic conditions.
Antigen-Antibody Complex↗
Characteristics of immune complexes detectable by two independent assays in gynaecological malignancies.
Immune complexes from patients with ovarian and endometrial cancer have been examined using the C1q solid phase (C1qSP) and polyethylene glycol (PEG) precipitation assays. The amount of IgG in the PEG precipitates was inversely correlated with the amount of IgM whilst the IgM values correlated positively with the C1qSP assay values. Separation studies revealed that most of the C1qSP activity was not precipitated from cancer sera by 2% PEG. The immune complexes were fractionated on Sephacryl S-300. Both the PEG precipitation and C1qSP assays detected high molecular weight immune complex like activity (greater than 19S). The C1qSP assay also detected a second peak of activity at approximately 7-8S. Most of the PEG detectable immune complexes from sera dissociated during column chromatography, whereas the C1qSP detectable complexes were relatively stable. Furthermore the IgG from fractionated PEG precipitates emerged as a monomer (7S) component. The PEG assay appeared to be detecting a high molecular weight complex containing mostly IgG rather than IgM with a low affinity for C1q, which was easily dissociated. The C1qSP assay detected a more stable high molecular weight complex containing a relatively high proportion of IgM and a low molecular weight complex, both with a high affinity for C1q.
Antigen-Antibody Complex↗
Anti-globulins and circulating complexes in early rheumatoid arthritis.
The importance of immunological parameters such as anti-globulins, anti-RANA and circulating immune complexes in rheumatoid arthritis (RA) has been studied by examining patients with early disease who are attending general practitioner clinics with joint pains for the first time. Anti-RANA, and IgG and IgM anti-globulins were detectable in the serum at the earliest time we were able to examine the patients. The anti-globulins had specificity for both rabbit and human IgG from the outset. Immune complexes were similarly raised in early disease. From these patients with early joint pains we were able to predict, by means of multivariant discriminant analysis of the laboratory data obtained from the first serum sample, between those who would develop into patients with classical or definite RA at 1 year and those who would have non-inflammatory joint disease.
Antibodies, Anti-Idiotypic↗
Sequential studies of circulating immune complexes in gynecological malignancies.
Immune complexes have been assayed sequentially in seventeen patients with gynecological malignancies, using a polyethylene glycol precipitation assay and a Clq solid phase assay. The PEG assay demonstrated a good correlation between PEG assay levels and the course of disease in nine out of eleven patients with ovarian adenocarcinoma and all four patients with endometrial carcinoma. Three of the patients with ovarian cancer were not treated with aggressive surgery and exhibited equivocal signs of progressive disease during subsequent follow-up. There was no clear relationship between immune complex levels and the clinical condition in two of these patients. The ClqSP assay result did not correlate with disease progression and, in several instances, progressive disease was associated with a fall in ClqSP values. In a further series, twelve out of twenty patients with ovarian cancer who were initially in remission from disease but subsequently relapsed demonstrated elevated levels of PEG immune complexes between one and three months before clinical detection of recurrence whereas patients who stayed in remission maintained normal levels of PEG immune complexes. These data suggest that the PEG assay may be of clinical value in the monitoring of ovarian cancer patients with minimal residual disease following surgery.
Adenocarcinoma↗
Idiotypic networks and their possible exploitation for manipulation of the immune response.
Explore the source record for details and available documents.
Animals↗