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Biomedical subjects

I Roitt

Publications and source records attributed to I Roitt.

11 recordsLinked to original sources

Agalactosyl IgG: an aid to differential diagnosis in early synovitis.

Sixty consecutive patients presenting with early-onset synovitis were studied by measuring rheumatoid factor (RF) titers and the percentage of oligosaccharide chains attached to the C gamma 2 domain of IgG that lack galactose (GAL[0]). After 2 years of followup, 39 patients (65%) had developed rheumatoid arthritis (RA), and 21 had developed a variety of other inflammatory joint diseases. A combination of RF positivity and GAL(0) levels above the age-corrected mean gave a positive predictive value for a diagnosis of RA in 94% of these patients. These observations may well have clinical utility.

Adult

Age-related galactosylation of the N-linked oligosaccharides of human serum IgG.

In a study of 151 normal, healthy individuals of both sexes varying in age from 1-70 yr, it was found that the relative incidence of agalactosyl (with both outer arms terminating in N-acetylglucosamine) N-linked oligosaccharides on total serum IgG decreased from birth to a minimum (at 25 yr of age) and then increased with age. The relative incidence of digalactosyl structures varied inversely to this, and the relative incidence of monogalactosyl structures was constant. Galactosylation of the N-linked oligosaccharides of the human serum IgG of normal individuals is therefore an age-related molecular parameter. Several reports have suggested that rheumatoid arthritis is associated with a decreased galactosylation of serum IgG (3-5). The normal variation in galactosylation with age as described here allows a true assessment of disease-associated changes in this parameter, and raises the possibility that one of the lesions in rheumatoid arthritis is an accelerated aging of the immune system. In addition, heterogeneity within age groups may be due to intrinsic differences in genetic endowment, or may reflect the impact of extrinsic factors (8).

Adolescent

A prognostic index for erosive changes in the hands, feet, and cervical spines in early rheumatoid arthritis.

Clinical and laboratory measurements taken at the onset of rheumatoid arthritis in 149 patients were compared with the severity of radiological changes seen at 3 years in the hands and feet, and cervical spine. The strongest association with the severity of peripheral radiological damage was rheumatoid factor (p less than 0.0001 for both the latex titre and RAHA titre). Subluxation of the cervical spine was associated only with the presence of HLA-Dw2 (p less than 0.02) and HLA-B7 cross-reacting group (p less than 0.02). Discriminant function analysis utilizing latex titre, RAHA titre, haemoglobin level, and platelet count predicted the development of erosive or nonerosive disease in 79%. This method was less successful in predicting the actual severity of erosive damage and was not improved by the addition of HLA data. Radiological outcome in the cervical spine was successfully predicted in 82% using HLA-Dw2, HLA-B27 and age of onset of disease. It is concluded that the best predictors of erosive disease were standard laboratory features measured at onset, but that more powerful discriminant factors are needed if these are to influence clinical practice. Further prospective studies will establish whether rheumatoid involvement of the cervical spine is an expression of the influence of HLA determinants in this disease.

Adult

High efficiency antigen presentation by thyroglobulin-primed murine splenic B cells.

B cells primed in vivo with mouse or rat thyroglobulin present these antigens at very low concentrations to CH9, an Ly 1+2- T cell hybridoma specific for mouse and rat thyroglobulin. Presentation measured by interleukin 2 release from CH9 is sensitive to treatment with a monoclonal antibody eliminating splenic B cells but is unaffected by anti-Thy-1.2 or 33D1 (which destroy T cells and dendritic cells, respectively). Presentation is specific for the priming antigen and is blocked by preincubation of the B cells with sheep anti-mouse F(ab')2. We suggest that in this system, primed B cells present thyroglobulin and that this may represent a means by which an initial triggering event priming both B and T cells could allow maintenance of autoreactive responses in vivo in the presence of low concentrations of circulating antigen.

Animals

A prospective study of early onset rheumatoid arthritis over fifteen years: prognostic features and outcome.

A total of 218 patients with early onset rheumatoid arthritis were entered into a prospective study over fifteen years. Of these, 151 remained in the study at three years (of whom 14 died), and a further 39 (23 deaths) defaulted after this time. The severity of disease was assessed by four different methods. Although persistently active joint disease was recorded in 26% of patients, only 13% had severe functional impairment, and only 14% developed severe erosions. An episode of RA lasting two to three years followed by complete remission with none or minimal sequelae ("non recurrent" RA) was present in 34%. Using discriminant analysis, which selected rheumatoid factor, haemoglobin level and platelet count from a number of clinical and laboratory variables measured at onset, it was possible to predict three mutually exclusive outcome categories correctly in 50-60% of patients depending on the method of assessment of outcome.

Adolescent

HLA antigen associations with radiological changes in the hands, feet, and cervical spines in early rheumatoid arthritis.

Clinical, laboratory, and genetic features measured at the onset of rheumatoid arthritis in 100 patients were compared with the severity of radiological changes in the hands and feet and in the cervical spines at a mean of 7.7 years. HLA-Dw4 was associated with more severe (p = 0.009) and HLA-Dw2 with less severe (p = 0.02)radiological changes in the hands and feet but the single strongest correlation with the severity of peripheral erosions was rheumatoid factor (p = less than 0.0001). Although none of the standard clinical or laboratory parameters correlated with severity of cervical spine changes, the presence of HLA-Dw2 and/or HLA B7 cross-reactive group were associated with more severe radiological changes in the cervical spine (p less than 0.02). Discriminant analysis selected certain standard laboratory parameters which in combination provided the most powerful prognostic index of radiological outcome in the hands and feet which was correct in 82 per cent. The addition of HLA data did not improve this figure. Conversely, the combination of the presence of HLA-Dw2, B27, and older age of onset of disease was found to be the most powerful predictor of the development of cervical spine changes and successfully predicted this complication of RA in 73 per cent.

Adult

Molecular analysis of induced idiotypes associated with autoanti-thyroglobulin.

Idiotype (Id) and autoanti-thyroglobulin were induced in different strains of mice by priming with anti-Id to monoclonal anti-thyroglobulins (D8 and G4) and challenged with a subimmunogenic dose of thyroglobulin (Tg). Both D8.Id and G4.Id were induced in CBA mice by priming with the appropriate anti-Id, but only priming with anti-D8.Id also induced an increase in anti-Tg. D8.Id was induced in other strains by the same schedule but it only appeared to be associated with anti-Tg in 129 and, to a lesser extent, BALB/c mice, both of which have the allotype Iga. The extent of the overlap between the D8 Id and the anti-Tg was estimated and shown to be greatest in the CBA strain from which the D8 clone was originally derived. Spectrotypic analysis of the induced Ids in CBA mice showed that some of the D8.Id, but none of the G4.Id, was identical to the original clonotype, implying that CBA mice normally have cells which can be induced to produce D8.Id-positive autoanti-Tg, which are normally weakly expressed or regulated. The observation that anti-D8.Id priming in some strains increased D8.Id-negative anti-Tg responses suggests that the D8.Id may also be associated with anti-Tg T-cells.

Animals