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Biomedical subjects

J B Winfield

Publications and source records attributed to J B Winfield.

At least 73 records · Page 4Linked to original sources
PubMed1983

Interpretation of cerebrospinal fluid protein assays in various neurologic diseases.

Albumin and immunoglobulin G (IgG) were determined in cerebrospinal fluid (CSF) and serum, and the CSF/serum albumin Index (CSF X 10(3)/serum albumin concentration ratio) and IgG Index [(CSF/serum IgG)/(CSF/serum albumin)] were calculated. Data for these indices and oligoclonal banding are described in 23 cases of multiple sclerosis (MS), 19 of systemic lupus erythematosus (SLE), eight of sarcoidosis, 48 cases of miscellaneous disease, and 25 control patients with nonspecific complaints. Of the MS, SLE, and sarcoidosis patient groups, 8.5%, 26%, and 12.5% showed an abnormally high CSF/serum albumin Index; 87%, 16%, and 0% an increased IgG Index; and 87.5%, 42% and 0% showed positive oligoclonal banding. IgG Index and oligoclonal banding results for MS patients differed significantly from the sarcoidosis (p less than .001) and SLE (p less than .05) groups. When the CSF/serum albumin Index is considered also, the control and sarcoidosis patient results differ significantly from the MS group (p less than .001 and p less than .01). A strong correlation between the IgG Index and oligoclonal banding is implicated.

Blood-Brain Barrier↗
PubMed1982

Association between endogenously activated T cells and immunoglobulin-secreting B cells in patients with active systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is characterized by increased numbers of circulating B cells activated polyclonally to secrete immunoglobulin. Because T cells secrete, or shed, various factors that are functionally important in regulating immunoglobulin production by B cells, a reverse hemolytic plaque assay was developed to quantitate such activated T cells. In this technique, we used a rabbit antiserum raised to supernatants of concanavalin-A--stimulated human lymphocytes. The relevant antigenic specificity of this antiserum is directed toward the shed surface membrane determinant(s) preferentially expressed on activated T cells. Freshly isolated peripheral blood mononuclear cells from 14 SLE patients contained more than 10 times the number of endogenously activated T cells than cells from normal subjects. Within the SLE group, plaque-forming T cells were particularly increased in patients with active disease. By linear regression analysis, a significant positive correlation was revealed between such activated T cells and immunoglobulin-secreting B cells, also measured by a reverse plaque assay (r = 0.83). It appears that both activated B cells and T cells circulate in increased numbers in SLE. Additional investigation will be required to define the molecular nature of the T cell product(s) being measured and to clarify the relationship of these findings to the immunoregulatory abnormalities in this disorder.

Animals↗
PubMed1982

Subclass restriction of anti-Sm antibodies in MRL mice.

The subclass distribution of anti-Sm antibodies in the serum of MRL/Mp-Ipr/Ipr and MRL/Mp- +/+ mice was investigated with a sensitive ELISA technique. In both strains, but particularly in the Ipr mice, anti-Sm antibodies were predominantly of the IgG2a isotype. This preponderance was not an artifact of the sensitivity or specificity of the subclass-specific anti-Sm ELISA, nor did it reflect the subclass distribution of total serum IgG. A plaque-forming cell assay for anti-Sm antibodies also showed a predominance of the IgG2a isotype, indicating that the serum findings could not be explained by differential catabolism of IgG subclasses. Finally, antibodies to double-stranded DNA, as detected by the Crithidia luciliae assay, did not show a restricted subclass distribution. The isotype expression of anti-Sm antibodies in MRL mice must reflect in vivo mechanisms regulating the production of these autoantibodies. The IgG2a restriction in particular suggests an important in vivo role for T cells.

Animals↗
PubMed1981

Age influences the clinical and serologic expression of systemic lupus erythematosus.

The clinical and serologic characteristics of 17 patients with onset of systemic lupus erythematosus (SLE) after age 50 were compared with those of 49 younger patients. All patients were followed prospectively for a mean duration of 47 months. A clinical and serological data base was established for each patient, and information collected at each visit to a lupus clinic was analyzed by computer. The clinical featured distinguishing old-age SLE were a low incidence of significant renal disease and prominent pleuropericarditis and arthritis throughout the period of followup. Serologic abnormalities were milder in older patients. Thus, hypocomplementemia, anti-DNA antibodies, and C1q precipitins occurred less frequently, and rheumatoid factor was more often present than in younger patients with SLE. Regression analysis suggested linear change in disease expression with age rather than distinct age-related subgroups.

Adult↗
PubMed1981

Studies of artificial cryoprecipitates containing anti-DNA antibody activity.

Artificial cryoprecipitates have been prepared from SLE sera by incubation of anti-double stranded DNA with 3H-PM2 DNA. IgM rheumatoid factor, and complement to study further the relationships between natural cryoprecipitation and the DNA/anti-DNA system in this disorder. Addition of rheumatoid factor and/or complement to a mixture of SLE serum and 3H-DNA results in increased precipitation of the 3H-DNA following incubation at 4 degrees C. Precipitation formed with added complement or complement plus rheumatoid factor could be rapidly resolubilized or reprecipitated by warming to 37 degrees C or recooling to 4 degrees C, i.e., exhibited the behavior of natural cryoprecipitates. The resolubilized cryoprecipitates contained excess antibody, because they bound significant quantities of additional 3H-DNA in the Farr assay. Of special interest was the observation that DNA binding activity frequently could be recovered from solubilized cryoprecipitates even though 3H-DNA was not added during the original cryoprecipitate preparation. With certain cryoprecipitations prepared in this way, the DNA binding activity was further increased by deoxyribonuclease treatment, raising the possibility that endogenous DNA may be constituent of such cryoprecipitates. The implications of these findings with respect to the nature of antibody-DNA immune complexes in SLE are discussed.

Antibodies, Antinuclear↗
PubMed1981

Nature of double-stranded DNA binding activity in seropositive rheumatoid arthritis: formation of low avidity DNA/rheumatoid factor/IgG/low density lipoprotein complexes.

Sera from majority of patients with seropositive rheumatoid arthritis, which generally lacked detectable anti-double stranded DNA in Farr, Crithidia luciliae, and microcomplement fixation assays, exhibited high levels of dsDNA binding in the presence of 3.5% polyethylene glycol when using intrinsically labeled 3H-PM2 DNA as antigen. Except for SLE, such increased dsDNA binding was absent in normal and a variety of other disease sera, including those from patients with seronegative rheumatoid arthritis. In contrast to the situation in SLE, in which dsDNA binding is mediated by specific anti-DNA antibody, the increased dsDNA binding activity in seropositive rheumatoid arthritis was shown to be dependent upon complex low avidity interactions involving DNA, IgG, IgM rheumatoid factor, and low density lipoproteins. Analysis of the composition of the polyethylene glycol serum precipitates by 2-dimensional gel diffusion, immunoelectrophoresis, and sodium dodecyl sulfate polyacrylamide gel electrophoresis failed to reveal the presence of additional DNA-binding proteins unique to seropositive rheumatoid arthritis. The only feature distinguishing high DNA binding sera from those with low DNA binding activity was an increased amount of polyethylene glycol-insoluble IgG in the former, presumably reflecting IgG/IgG and/or IgG/IgM complexes. The significance of these unusual DNA/low density lipoprotein/IgG/rheumatoid factor complexes with respect to the diagnostic specificity and pathophysiology of the DNA/anti-DNA system is discussed.

Antibody Affinity↗
PubMed1981

Activated T cells in human peripheral blood: quantitation with a reverse hemolytic plaque assay.

Rabbit antiserum to culture supernatant of concanavalin A-stimulated peripheral blood mononuclear cells was used in a reverse hemolytic plaque assay to detect activated T lymphocytes in human peripheral blood. The number of plaque-forming cells in fresh, unstimulated lymphocyte preparations was approximately 400/10(6) cells, and increased 7- to 14-fold after stimulation with a variety of mitogens and antigens. The kinetics of the increase paralleled 3H-thymidine incorporation, with a maximum on day 3 of culture. Plaques were eliminated by treatment of cells with anti-Leu-I + complement or by depletion of E-rosettes. The activated T cells were not restricted to a given inducer, suppressor, or Ia+ T cell subset, however. Both mitogen-stimulated culture supernatants and mitogen-activated lymphocytes, but not resting lymphocytes, were effective in absorbing the capacity of the rabbit antiserum to develop plaques. This suggested that the predominant specificity of this antiserum was directed toward surface membrane determinant(s) of T cells actively shed into the medium. This process was shown to require ongoing protein synthesis, and, in mitogen-stimulated lymphocyte preparations, DNA synthesis as well. This approach has enabled detection of a surprisingly large number of endogenously activated T cells in normal human blood, and should be useful for the analysis of immunoregulatory events at the single-cell level.

Animals↗
PubMed1979

Tgamma cells in systemic lupus erythematosus. Variation with disease activity.

Circulating T cells bearing receptors for the Fc portion of IgG (T gamma) were identified by sensitive immunofluorescent techniques with rabbit IgG b4 allotype/anti-b4 complexes. A twofold decrease in both proportion and absolute number of T gamma cells was found in patients with active systemic lupus erythematosus (SLE) relative to values obtained during disease remission. The reduction in T gamma cells was most evident in patients with severe hypocomplementemia. A deficit of T gamma cells in active patients was not demonstrated. The percentage of total T cells rosetting with sheep erythrocytes was reduced in peripheral blood of most patients regardless of disease activity status, but particularly during SLE exacerbation. Cells lacking intrinsic surface immunoglobulin, IgG Fc receptors, and receptors for sheep erythrocytes were increased. These cells, operationally termed null, exhibited an inverse linear relationship with T cells that was not apparent in regression analyses performed against other lymphocyte subpopulations. Such differences were not found for B cells and IgG receptor-bearing non-B/non-T cells which were present in normal proportions in virtually all patients. The origin and functional significance of these unusual lymphocyte subpopulation abnormalities are discussed.

B-Lymphocytes↗
PubMed1979

Association of IgG anti-brain antibodies with central nervous system dysfunction in systemic lupus erythematosus.

Sera from 20 patients with systemic lupus erythematosus (SLE) and active central nervous system (CNS) dysfunction were examined by indirect immunofluorescence for antibodies to neuronal membrane determinants. Warm-reactive IgG antibodies were demonstrable in 82% (9/11) of patients with clinical evidence for seizures or diffuse CNS disease, but these antibodies generally were absent in non-CNS SLE sera or when focal neurologic deficit or psychosis was the primary CNS manifestation. Cold-reactive antibodies of the IgM class were equally prevalent in patients with or without CNS disease and appeared to be more directly correlated with extra-CNS systemic illness. Absorption experiments with lymphocytes, brain homogenate, and various other tissues suggested a predominant brain-specificity for IgG antibodies and partial lymphocyte cross-reactivity for IgM antibodies. Interpretations of this special association between IgG anti-brain antibodies and diffuse CNS dysfunction in SLE are discussed.

Autoantibodies↗
PubMed1978

Serologic studies in patients with systemic lupus erythematosus and central nervous system dysfunction.

Serologic studies were performed on 25 patients with systemic lupus erythematosus (SLE) during 29 acute episodes of central nervous system (CNS) disease. Increased anti-DNA antibody and decreased total serum hemolytic complement activity were observed only in those patients with associated extra-CNS disease manifestations. Patients with isolated CNS disease were otherwise in apparent clinical and serological remission regarding these two indices. No special association of cold-reactive IgM antilymphocyte antibodies was demonstrable in patients with ongoing CNS injury. Of special interest was an increased incidence of anti-Sm antibodies in the patients with CNS dysfunction relative to that in a large group of patients without neuropsychiatric disease. The incidence of anti-RNP was not increased. The data do not support direct involvement in SLE brain injury of either DNA/anti-DNA complexes or of lymphocytotoxic antibodies cross-reactive with brain cells, but do suggest an association of anti-Sm with CNS disease in this disorder.

Antibodies↗
PubMed1977

Utility of protease-digested human peripheral blood lymphocytes for the detection of lymphocyte-reactive alloantibodies by indirect immunofluorescence.

Human peripheral blood lymphocytes were digested briefly with protease prior to application of indirect immunofluorescence techniques for detecting alloantibodies in sera of patients with chronic renal failure on maintenance hemodialysis. Background staining of intrinsic surface IgM and cytophilic IgG bound to Fc receptors was eliminated or greatly reduced, enabling detection of B cell specific antibodies, including cold-reactive types not demonstrable by conventional immunofluorescence or complement-dependent lymphocytotoxicity. The antigenicity of HLA and other surface membrane determinants was not decreased by protease, although reactivity with certain sera was enhanced. In experiments comparing indirect immunofluorescence using protease-treated cells with complement-dependent lymphocytotoxicity and antibody-dependent, lymphocyte-mediated cytotoxicity assays, indirect immunofluorescence was more sensitive and comprehensive, but not less specific, in defining alloantibodies of a variety of types.

Cytotoxicity Tests, Immunologic↗
PubMed1977

Avidity of anti-DNA antibodies in serum and IgG glomerular eluates from patients with systemic lupus erythematosus. Association of high avidity antinative DNA antibody with glomerulonephritis.

Significant differences in both specificity and avidity of anti-DNA antibodies were observed in the sera of groups of patients with active systemic lupus erythematosus glomerulonephritis, active systemic lupus erythematosus without nephritis, and in IgG eluates obtained by DNAase digestion of isolated glomeruli from glomerulonephritic kidneys. With methylated albumin-kieselguhr fractionated 3H-HeLa DNA as a source of native or single-strand DNA antigen in a modified Farr assay, an increased level of antibody to native DNA was associated with active systemic lupus erythematosus, particularly active nephritis. The avidity of antinative DNA estimated from plots of the reciprocals of bound and free antigen according to the Sips distribution formula was significanly lower in active glomerulonephritis sera than in sera from patients with active systemic lupus erythematosus without nephritis. However, antinative DNA of uniformly high avidity was found in the glomerular eluates. Avidity of single-strand DNA antibodies did not differ in the various patient groups. The data stronly supprot a major role for high avidity antinative-DNA in DNA/antiDNA immune complex-induced glomerular injury in systemic lupus erythematosus.

Antibodies, Anti-Idiotypic↗
PubMed1977

Fc receptor heterogeneity: immunofluorescent studies of B, T, and "third population" lymphocytes in human blood with rabbit IgG b4/anti-b4 complexes.

IgG Fc receptors on human peripheral blood lymphocytes (PBL) were characterized by immunofluorescence studies with defined rabbit IgG b4 allotype/anti-allotype complexes. Three discrete types of Fc receptor-bearing cells, totaling approximately 33% of PBL, were identified. Fc receptors of the three types differed in their sensitivity to trypsin and in either absolute or localized density (topography) as determined by variable requirements for anti-IgC cross-linking in order to visualize bound complexes microscopically. The question of additional heterogeneity related to differences in individual Fc receptor affinity for complexed IgG was not approached in this study. Ten to 15% of PBL had pronase-sensitive, trypsin-resistant Fc receptors readily detected by direct immunofluorescence by using large fluorescein-conjugated complexes prepared near equivalence. Double label and lymphocyte fractionation experiments established this population to be largely distinct from suface IgM+ B cells and T cells, and identical to EA Ripley rosette-forming cells. Approximately 50% of surface IgM+ B cells and approximately 10% of T cells had lower density Fc receptors identified by indirect immunofluorescence with small complexes prepared in antigen excess or by cross-linking fluorescein-conjugated complexes with anti-rabbit IgG anti-serum. An additional approximately 15% peripheral T and B cells had very low density Fc receptors detectable by complexing the IgG on the cell surface by sequential incubations of cells with b4 IgG and anti-b4. Fc receptors on B and T cells were sensitive to both pronase and trypsin digestion. The heterogeneity of IgG Fc receptors on different lymphocyte subpopulations as defined by these these experiments may be of relevance for further analysis of normal and abnormal immune function.

Animals↗