Clinical manifestations of scleroderma.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to P L Haber.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
To identify whether sera containing antinuclear antibody (ANA) from patients with juvenile rheumatoid arthritis (JRA) recognize a common antigen, extracts of HeLa nuclei were prepared by incubating the nuclei with buffers of sequentially increasing salt concentrations (0.1 M, 0.3 M, and 0.5 M NaCl). Western blot analysis using sera from 82 patients with JRA revealed that 63% of ANA positive JRA sera reacted with 2 bands (50-40 kDa) in the 0.3 M extract whereas only 14% of ANA negative JRA sera had antibody to these bands. Antibody to the 50-40 kDa antigen(s) strongly correlated with the presence of ANA by immunofluorescence and was found in 70% of patients with iritis; however, it did not correlate with disease subgroup or disease activity.
Previous studies have demonstrated that J chain is expressed not only in cells that produce polymeric immunoglobulins, but also in those engaged in synthesis of monomers including IgG and IgD. The presence of J chain in these cells suggested that its role may not be restricted to the formation of polymers. For the present study, fluorochrome-labeled polyclonal anti-J-chain and monoclonal antibodies to IgG subclasses were used to determine the distribution of J chain in IgG plasma cells from normal human tissues and from pokeweed mitogen (PWM)-stimulated human peripheral blood lymphocytes. The results indicate that J chain is not equally distributed among cells producing different IgG subclasses. The percentages of PWM-stimulated cells containing J chain were: 22 +/- 5 (SE) for IgG1, 49 +/- 6 for IgG2, 17 +/- 7 for IgG3, and 64 +/- 11 for IgG4. Examination of sections of various human lymphoid tissues revealed that the frequency of IgG cells that coexpressed J chain was lower than that observed in the PWM system and displayed variable distribution among IgG subclasses. The frequency of J-chain expression in IgG-producing cells may be related to the degree of cellular maturation and may differ according to the origin of cells.
The distribution of IgG and IgA subclass plasma cells among dissociated synovial cells from 14 rheumatoid arthritis (RA) synovia was examined by immunofluorescence using mouse monoclonal anti-human subclass antibodies. Of the IgG plasma cells 81 +/- 9% were IgG1, 4 +/- 2% IgG2, 14 +/- 9% IgG3, and 0.9 +/- 0.6% IgG4. While IgG1 predominated in all 14 synovia (which is similar to what is seen in normal tissues), in 5/14 20% or greater of IgG plasma cells were IgG3, suggesting a selective increase in IgG3 production in the synovia of certain RA patients. Among IgA plasma cells 89 +/- 5% were IgA1 and 8 +/- 3% were IgA2. This distribution is similar to the distribution in normal serum.
Epstein-Barr virus (EBV) transformation was used to examine the differentiation potential of circulating B cells from eight individuals with late-onset panhypogammaglobulinemia. Cytoplasmic and secreted immunoglobulins were evaluated by immunofluorescence and radioimmunoassay. EBV-infected cultures of B cells from patients and healthy controls generated similar numbers of IgM-secreting plasma cells, but relatively few IgG and IgA plasma cells were induced in cultures of patients' B cells. As further evidence of B-cell immaturity, approximately 90% of the IgA B cells in the eight patients coexpressed IgM. Clonal diversity of B cells from hypogammaglobulinemic patients was examined with a panel of mouse monoclonal antibodies directed against idiotypic and VH subgroup determinants. The frequencies of EBV-induced plasma cells exhibiting the different idiotypic and VH determinants were similar for patients and controls. The data suggest the continued generation of clonally diverse B cells that are capable of terminal plasma-cell differentiation when the normal triggering mechanisms are bypassed by EBV. The arrested differentiation at an immature B-cell stage in these hypogammaglobulinemic individuals would appear to reflect a defect in normal B-cell triggering.