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I M Roitt

Publications and source records attributed to I M Roitt.

At least 73 records · Page 4Linked to original sources
PubMed1986

HLA and rheumatoid arthritis: a combined analysis of 440 British patients.

Four hundred and forty unrelated British Caucasoid patients with rheumatoid arthritis (RA) have been HLA typed for class I and class II antigens. Analyses of HLA antigen associations were performed on the overall group and in patient subsets selected according to particular disease parameters or sex, or both. The results confirm previously reported positive associations of HLA-DR4, Dw4, and DRw53 and negative associations of HLA-DR2 and DR7 with RA. Patients subsets with severe erosions, seropositivity, and features of extra-articular disease showed a stronger association, also confirming earlier reports. The link between HLA and disease severity was emphasised by a significant trend of increased Dw4 frequency with increasing severity of radiological erosions. In addition, a positive association of RA with HLA-A2 was observed and a strong negative association with DR3. The frequency of HLA-B27 was significantly increased in patients with subluxation of the spine. Differences were observed between male and female patients in relation to the HLA association. In men an increase in the frequency of the haplotype HLA/Dw4/DR4/Bw62/Cw3/A2 was observed. This showed no relationship with parameters of disease severity other than extra-articular disease. In women only class II antigens (DRw53/Dw4/DR4) showed an increased frequency. This increase was strongly associated with disease severity. A significant decrease of this class II association was observed with increasing age of disease onset; this was not seen in men.

Adolescent↗
PubMed1986

Helper and suppressor activities of an autoreactive mouse thyroglobulin-specific T-cell clone.

An autoreactive T-cell clone, MTg9B3, specific for mouse thyroglobulin, has been characterized. This clone has properties consistent with it an being autoreactive T helper cell. It is I-A restricted, with a surface phenotype of Thy 1+, L3T4+, Ly2-, and produces a number of non-specific lymphokine activities following specific triggering with antigen. Furthermore, antigen-stimulated clone cells were capable of providing bystander help in SRBC-specific antibody responses. Surprisingly, MTg9B3 cells had a profound suppressive effect on thyroglobulin autoantibody responses in vitro.

Animals↗
PubMed1986

HLA frequency and haplotype analysis in a family study of adult onset rheumatoid arthritis.

Twenty-five families with probands who have rheumatoid arthritis (RA) were studied for clinical evidence of disease and for HLA status. This confirmed an association between RA and DR4 in 19/25 probands (76 per cent, p = 0.008). These 19 probands carried 24 haplotypes which contained DR4. There was no significant increase of DR4 haplotypes bearing B15(Bw62) or B44 when compared with published control haplotype data. The rare complement allele C4 B3 was detected as part of the extended haplotype A2 Cw3 B15(Bw62) DR4 C4 A*3B*3 in three probands with severe RA. Further studies to examine disease severity and autoantibody expression are in progress.

Arthritis, Rheumatoid↗
PubMed1986

Characterization of monoclonal antibodies directed towards the microsomal/microvillar thyroid autoantigen recognized by Hashimoto autoantibodies.

Monoclonal antibodies reacting with thyroid microsomes have been described. In this report, we present evidence that some of these monoclonal antibodies (MoAb) MAH C3 and perhaps MAH C6 are directed towards the thyroid microsomal antigen towards which microsomal autoantibodies from Hashimoto patients are directed. Immunofluorescence on cryostat sections with MAH C3 and MAH C6 on thyroid gland gave cytoplasmic staining patterns that were comparable to those obtained with autoantibodies. By western blotting, reactivity of MAH C3 was shown to be directed towards a 105,000 mol. wt component, comparable to that recognized by autoantibodies by immunoprecipitation. Double immunofluorescence with MAH C3 and autoantibodies on cultured, viable thyroid monolayers revealed a large number of comparable binding sites; in contrast, binding sites for asioloagalactothyroglobulin were different of binding of MAH C3 by the autoantibodies suggesting that the epitopes recognized were different. This was confirmed with the use of a rat thyroid cell line FRTL-5 and fluorescence activated cell sorter analysis which showed binding to the rat microsomal component with autoantibodies but negligible binding with MAH C3 and MAH C6. It therefore appears that the monoclonal antibodies recognize species specific determinants while the autoantibodies recognize species cross reactive determinants. These monoclonal antibodies will be useful for purification and immunochemical analysis of this autoantigen in human thyroid disease.

Animals↗
PubMed1985

Structural features of the autoantigens involved in thyroid autoimmune disease: the thyroid microsomal/microvillar antigen.

The microsomal/microvillar antigen of the human thyroid gland which provokes thyroid autoimmunity was characterised by immunoprecipitation studies. Sera from patients with Hashimoto's thyroiditis, primary myxoedema or Graves' disease containing autoanti-microsomal antibody specifically precipitated a component, which under reducing conditions migrates with a mol. wt of 105,000 on SDS-polyacrylamide gel electrophoresis. This protein was absent in auto- or xeno-anti-thyroglobulin precipitates, which under reducing conditions display four polypeptides of Mr 260,000, 230,000, 180,000 and 142,000. Under non-reducing conditions, the microsomal/microvillar antigen displayed a small shift in mobility to a mol. wt of 117,000 suggesting the presence of intrachain disulphide bonds. In contrast, under these conditions, anti-thyroglobulin precipitated components displaying polypeptides of approx. mol. wts in the region of 240,000-260,000, 170,000-180,000 and 140,000. Absorption of thyroiditis sera on thyroglobulin-Sepharose followed by immunoprecipitation abolished the anti-thyroglobulin components without affecting the binding of the 105,000-dalton polypeptide, if the sera contained antimicrosomal antibody. No comparable material was identified in microsomal membrane preparations prepared from the stomach which is also commonly involved in organ-specific autoimmunity. The 105,000-dalton component does not bind to a Lens culinaris lectin affinity column. We conclude that the epitopes of the microsomal/microvillar antigen are presented on a poorly glycosylated peptide of mol. wt 105,000, which is probably stabilised by intrachain disulphide bonds and which does not share serological reactivity with membrane-bound thyroglobulin.

Antigens↗
PubMed1985

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↗
PubMed1985

Autoreactive T-cell lines specific for mouse thyroglobulin.

Autoreactive T-cell specific for mouse thyroglobulin have been established and characterized. These Lyt 1+ T cells proliferated specifically in response to thyroglobulin presented by syngeneic irradiated spleen cells. The antigen-presenting cell requirements of these autoreactive T cells appeared to be the same as those for foreign antigen (PPD) reactive T cells. All lines tested required antigen-presenting cells compatible at the I-A subregion of the H-2 complex. Both T-cell types responded to antigen presented by peritoneal cells and splenic dendritic cells, but only gave optimal responses when whole spleen cells were used. The cross-reactivity patterns of responses to mouse, rat, pig and human thyroglobulins indicated that at least two different epitopes could be recognized by the autoreactive T cells. Furthermore, these epitopes appeared to be different from those recognized by the majority of serum autoantibodies to mouse thyroglobulin.

Animals↗
PubMed1985

[Preponderant synthesis of rheumatoid factors by synovial plasma cells in rheumatoid polyarthritis].

Plasma cells synthesising rheumatoid factor have been identified by immunofluorescent studies of sections of cells eluted from synovial membranes poor in macrophages. More than 90% of the IgM plasma cells produce rheumatoid factor, while 50 to 60% of IgG plasma cells and only 10% of IgA plasma cells produce rheumatoid factor. The equivalent results obtained in patients with sero-positive and sero-negative rheumatoid arthritis suggest that auto-immunisation between the IgG plays the same determinant role in the pathophysiology of the two types of rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1984

The thyroid "microsomal" antibody revisited. Its paradoxical binding in vivo to the apical surface of the follicular epithelium.

We have shown that thyroid monolayers derived from the glands of patients with autoimmune thyroid disease have immunoglobulin (Ig) bound to their surface. This appears to have been deposited in vivo rather than during preparation of the monolayers, a view supported by our finding of such deposits on the apical margin of follicular cells in sections cut from these glands and stained with conjugated anti-immunoglobulin. It is likely that these deposits represent specific binding of so-called "microsomal" autoantibodies to the surface of the thyroid cells in vivo since staining of partially disrupted follicles ("half-melons") with Hashimoto serum containing microsomal autoantibodies in the indirect immunofluorescence (IFL) test, localized the antigen on the apical surface of the cells lining the follicular cavity. Thus, paradoxically, although the antigen is relatively inaccessible, autoantibodies do reach and combine with the thyroid surface in vivo and may therefore play a role in pathogenesis.

Autoantibodies↗
PubMed1984

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↗
PubMed1984

A common epitope identified by a monoclonal antibody, MID 2, present on all leucocytes and associated with a group of high molecular weight glycopeptides.

A monoclonal antibody, MID 2, which reacts with an epitope common to all human leucocytes, was used to show that the leucocyte common antigen can be resolved into four glycoprotein components with molecular weights of 220 K, 200 K, 180 K and 160 K. The 200, 180 and 160 K peptides were all present to various extents in the T and B lymphoblastoid cell lines examined, but the 220 K component was only detected in the B-cell lines. The 220 K glycoprotein was also lacking in human thymocytes, but evidence of its expression in peripheral blood T lymphocytes was obtained, suggesting that it might be acquired as the cells differentiated. The four glycoproteins isolated from tonsil cells gave similar patterns on peptide mapping by the Cleveland enzymatic method or by cyanogen bromide cleavage, indicating extensive homology. It is conceivable that they differ from each other by the acquisition of similar repeating domain sequences of approximately 20 K. Alternatively, they may share a common peptide structure but differ in their electrophoretic behaviour in SDS gels owing to differences in carbohydrate; if this is the case, however, experiments with tunicamycin suggest that O-linked oligosaccharides must be involved.

Animals↗
PubMed1984

Specificity of plasma cells in the rheumatoid synovium. I. Immunoglobulin class of antiglobulin-producing cells.

Plasma cells synthesizing rheumatoid factors (RF) were identified by fluorescent staining of sections of synovium and macrophage-depleted cells from dispersed synovial tissue. The latter avoided problems related to sampling errors in studying tissue sections and in the uncertainty raised by the staining of macrophages with intracellular complexes. Plasma cells producing IgG predominated, and seropositive patients had a higher proportion of IgM producers than seronegative subjects. None the less, in both groups of patients more than 90% of the IgM plasma cells were synthesizing RF, whereas the corresponding figure for IgG was between 50% and 60%. Only around 10% of IgA plasma cells were positive for RF. The high percentage of IgM plasma cells making RF would tend to argue for an IgG-specific response and against direct polyclonal activation as the stimulus. The percentage of IgG-producing cells positive for RF is also consistent with a dominant response to IgG. Accepting the difference in the relative proportion of total IgM- to IgG-producing plasma cells in seropositive as against seronegative patients, the close similarity between the two groups in the fraction of cells making RF favours the view that the two groups have a comparable underlying immunopathology dependent on IgG autosensitization. From the technical standpoint, the dispersed cell method gives results in line with those obtained with sections but which are easier to read, whereas the fluorescent techniques described give clear and reproducible results for the detection of RF of different heavy-chain isotype.

Adult↗
PubMed1984

Asialoagalactothyroglobulin binds to the surface of human thyroid cells at a site distinct from the 'microsomal' autoantigen.

Human thyroglobulin has been shown for the first time to bind to the surface of cultured human thyroid follicular cells. Binding was only observed with partially glycosylated asialoagalactothyroglobulin, not with the fully glycosylated iodoprotein. The binding site for asialoagalactothyroglobulin in the cell membrane is distinct from membrane associated microsomal/microvilli antigen. Since asialoagalactothyroglobulin bears the autoantigenic determinants of the parent molecule, its ability to bind to the thyroid cell surface suggests a possible role for this protein in the pathogenesis of human thyroiditis.

Antigens↗
PubMed1984

Idiotypic determinants on human thyroglobulin autoantibodies derived from the serum of Hashimoto patients and EB virus transformed cell lines.

Rabbit anti-idiotypic reagents were prepared against three different human serum autoantibodies to thyroglobulin (Tg). Two of the rabbit antisera recognized private idiotypes (IdI) whilst a third antiserum recognized both an IdI and a cross-reactive idiotype (IdX) which was expressed in 50% of Hashimoto patients tested. A fourth anti-idiotype was produced against an IgM anti-Tg secreted by a patient's Epstein-Barr (EB) virus transformed lymphocytes. This antiserum only reacted with the immunizing IgM anti-Tg and therefore also recognized a private idiotype. Both the private and the public idiotypes appear to be restricted to the anti-Tg set of antibodies; this would favour the view that the IdX represents a collection of idotopes with the ability to bind Tg as their common feature, rather than a common structure based upon closely similar germ line derived amino acid sequences.

Animals↗