Antibody to discrete areas of the brain in normal individuals and patients with schizophrenia.
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Antibody Specificity↗
Biomedical subjects
R H Kelly
Publications and source records attributed to R H Kelly.
Clinical and laboratory evidence of autoimmunity in acute schizophrenia.
A number of assays were performed to assess immunologic function in 28 patients with clinically well-defined schizophrenia. Our data provide laboratory evidence that patients with schizophrenia have characteristics consistent with an autoimmune process, directed to components of the brain, which may participate in either the pathogenesis or etiology of schizophrenia. One-third of our patients had a clinically evident autoimmune syndrome unrelated to their psychiatric illness. Of the nine patients with an autoimmune disease, two had one autoantibody in their serum and five had more than one autoantibodies. Twelve of eighteen patients without clinical evidence of autoimmune disease had no detectable autoantibodies. Mitogenic responses to PHA and PWM were significantly reduced in the patient population when compared to controls. Fifty percent of the patients had an increased percentage (greater than 5%) of blood-borne HLA-DR (+) OKT4 (+) T-helper lymphocytes. Immune reactivity toward brain antigens was sought by measuring lymphocyte transformation to a saline extract of frontal lobe, and by immunoblotting of antigens extracted from frontal lobe, cingulate gyrus, interventricular septum, and hippocampus. Lymphocyte transformation did not reveal differences between patient and control groups. Normal sera were found to contain antibody to some of these brain antigens. However, patients with schizophrenia had antibody to antigens of the hippocampus, septal region and cingulate gyrus which were not encountered during analysis of normal sera.
Acute Disease↗
Anti-hormonal and anti-nuclear antibody (ANA) responses of mice immunized with estradiol.
Sera of female mice, immunized with estradiol-albumin conjugates, were tested for restricted heterogeneity of the anti-estradiol antibody response and for the development of antinuclear antibody (ANA). We found sera with the highest estradiol binding capacity gave clear evidence of clonal dominance when analyzed by isoelectric focusing. A sub-set of the immunized animals, approximately one-third, developed positive ANA serologies within 12 weeks of the primary immunization. All positive sera gave homogeneous patterns of staining in an avidin-biotin amplified indirect immunofluorescence assay. Our results point to a spontaneous production of ANA in at least some animals immunized with a ligand which binds to a nuclear receptor.
Animals↗
Stability of model immune complexes during zone electrophoresis and isoelectric focusing in agarose gels.
We evaluated the stability of model immune complexes, consisting of radioiodinated follitropin (125I-FSH), bound either to a mouse monoclonal antibody to FSH or to sheep polyvalent anti-FSH antiserum, during zone electrophoresis and isoelectric focusing in agarose gels. The complexes were relatively stable during zone electrophoresis at conventional voltages (less than 40 V/cm), about 80% of the initially bound antigen migrating in the gamma region. Highter voltages resulted in a linear increase in the antigen stripped from the gamma region. By contrast, isoelectric focusing very effectively dissociated the acidic 125I-FSH from the basic sheep immunoglobulins, even if the complexes were subjected to electromotive forces alone, i.e., by loading them onto the neutral region of the gel. The monoclonal complexes were not dissociated by high voltage alone. The monoclonal complexes could be completely dissociated by loading them at the anode, where gel acidification enhances complex dissociation. These observations can form the basis of a simple technique for isolating and dissociating human immune complexes before Western immunoblot analysis. Furthermore, the ease and rapidity with which bound and free antigen can be separated during zone electrophoresis in agarose suggests that this technique may have some application in clinical immunoassays.
Animals↗
Systemic lupus erythematosus: a role for anti-receptor antibodies?
Systemic lupus erythematosus (SLE) is considered by many to represent the best example of human disease where immune complexes play a primary role in the pathogenesis. SLE is thought to have an autoimmune basis; a conclusion based largely upon the propensity of these patients to form antibodies to cell nuclear components. The etiology of SLE remains unknown, as does the mechanism by which nuclear components are rendered autoantigenic. Here we present an argument for considering SLE as an antireceptor autoimmune disease, analogous to Graves' disease or myasthenia gravis. The proposed target of autoimmune attack, the estrogen receptor (ER), is normally resident in the nucleus, physiologically more active in women, and shed from hormonally responsive tissues during the course of the menstrual cycle. Autoantigenicity of ER is enhanced in SLE patients owing to a biochemical abnormality of estrogen metabolism which favors ligand occupancy of the receptor. The spectrum of anti-nuclear antibodies characteristic of SLE arises via normally functioning immune network regulatory mechanisms.
Antigen-Antibody Complex↗
CSF alpha 2-macroglobulin and C-reactive protein as aids to rapid diagnosis of acute bacterial meningitis.
alpha 2-Macroglobulin (AMG) and C-reactive protein (CRP) levels in cerebrospinal fluid (CSF) of patients with bacterial and aseptic meningitis have been analyzed by a rate nephelometric method to determine if these acute phase proteins can aid in differentiation of bacterial from aseptic meningitis. The mean CSF concentrations of AMG and CRP were 15 and 3.5 times greater, respectively, in the bacterial compared to the aseptic meningitis group. Also, the range of AMG levels showed minimal overlap between the two groups. The elevated levels of the proteins persisted after CSF cultures became negative. Quantitation of specific acute phase proteins in CSF may assist the differentiation of bacterial from aseptic meningitis.
Adolescent↗
Benign monoclonal gammopathy: a reassessment of the problem.
Disease associations of clonally restricted serum immunoglobulin (Ig) abnormalities were examined using methods for detecting and characterizing homogeneous Ig that are approximately forty times more sensitive than either cellulose acetate zone electrophoresis or immunoelectrophoresis. Medical records of three hundred five patients with clonally-restricted serum immunoglobulins, including 100 monoclonal gammopathies, and 205 immune complex/oligoclonal patterns were reviewed to obtain the attending physician's discharge diagnosis. Our data confirm lymphoproliferative disorders as the most frequent cause of monoclonal gammopathy (63% of our cases). However, in contrast to earlier reports, we found little evidence to support an association between monoclonal gammopathy and non-reticular malignancy. This does not mean our patients with these disorders had normal serum immunoglobulin patterns; rather, their qualitative abnormalities were, for the most part, not monoclonal. Instead, patients with these diseases had a high incidence of serum immune complexes and their antibody excess sequelae, oligoclonal patterns. Oligoclonal responses are noteworthy because Ig products of the individual clones do not always achieve equivalent serum concentrations, nor are the various clonal products synchronized with respect to the time at which they attain peak concentration. This creates a number of problems for laboratories attempting to characterize such abnormalities; 1) some analytical methods may only be capable of detecting the dominant clone of an oligoclonal pattern, and 2) analysis of a single specimen may yield erroneous results because the unique waxing and waning kinetic pattern of oligoclonal responses may preclude identification of all components at a single time point. We conclude that benign "monoclonal" gammopathies and circulating immune complex/oligoclonal Ig abnormalities occur in the same clinical situations and may be synonymous. The sensitivity of an individual laboratory's analytical methods would then determine which name is applied.
Age Factors↗
Alcoholism. A diagnostic and therapeutic challenge.
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Alcoholism↗
Clinical significance of immunologic and immunogenetic evaluation in multiple sclerosis.
One hundred thirty-two patients were separated into clinically defined groups of definite, probable and possible multiple sclerosis (MS), the spinal cord variant of MS (SCV), and non MS neurologic disease. HLA antigens A3 and B7 occurred at increased frequencies in definite and probably MS patients when compared with neurologic controls and healthy adults. CSF elevations of either kappa/lambda ratio, IgG/total protein ratio, or IgG were seen in 65% of the definite, probable and SCV groups. Patients with HLA A3 and B7 antigens had a higher than predicted incidence of elevated kappa/lambda ratio, suggesting that there may be immunogenetic control mechanisms which influence this CSF parameter. Neither HLA antigens nor CSF protein abnormalities correlated with the age of onset, progression, or degree of disability of disease, thus limiting their prognostic usefulness.
Adolescent↗
Chloramphenicol sodium succinate in the horse: serum, synovial, peritoneal, and urine concentrations after single-dose intravenous administration.
Six healthy adult mares were given a single IV dose (25 mg/kg of body weight) of chloramphenicol sodium succinate. Chloramphenicol concentrations in serum, synovial fluid, peritoneal fluid, and urine were measured serially over a 48-hour period. The highest measured serum chloramphenicol concentration was 6.21 micrograms/ml at 0.5 hour. Chloramphenicol was detected in synovial and peritoneal fluids, with mean peak concentrations of 3.89 micrograms/ml and 3.50 micrograms/ml, respectively, at 0.5 hour. Serum and synovial concentrations declined rapidly and were not measurable at 3 hours. Chloramphenicol could not be detected in peritoneal fluid at 6 hours. The serum half-life was 0.43 hour and the apparent volume of distribution was 2.83 L/kg. Urine concentrations of chloramphenicol peaked at 0.5 hour at 106.72 micrograms/ml and also declined rapidly. The drug could not be detected in the urine at 36 hours.
Animals↗
Autoantigens in an immunological network.
An autoantigen network, consisting of all non-lymphoid cells and a subset of peripherally located autoregulatory lymphocytes, is proposed. By equilibrating a web of idiotypic stimulation (helper activity) and antiidiotypic inhibition (suppressor activity) directed at each tissue differentiation antigen, this network quantitatively limits autoantigen expression and thereby regulates the differentiation and growth homeostatic processes these autoantigens mediate. Perturbations of the network's dynamic equilibrium secondary to viral infection, somatic mutation, or interaction with environmental agents would clinically manifest themselves as autoimmune tissue destruction, benign or malignant nonlymphoid neoplasia, and lymphoproliferative disorders.
Antigens↗
Effect of agents which block steroid receptor-DNA interaction on anti-DNA antibody titers in sera of patients with systemic lupus erythematosus.
We studied whether agents capable of blocking the interaction between steroid receptors and DNA could inhibit the serologic reactivity of anti-nuclear, and other, autoantibodies found in sera of humans with autoimmune disease. Conventional immunofluorescence procedures were used for both detection and titration of these autoantibodies. Parallel studies were conducted with sera diluted in buffers containing the inhibitory agents; KCl, Na2MoO4 or 1,10-phenanthroline, at optimal or suboptimal levels for blocking the steroid receptor-DNA interaction. In most cases these agents had no significant effect on the titer of autoantibodies present in human sera. However, there was one notable exception, that of autoantibodies to native DNA found in sera of patients' with systemic lupus erythematosus and detected by indirect immunofluorescence using Crithidia luciliae kinetoplast DNA as substrate. Here these agents caused either total inhibition of serologic reactivity at optimal blocking concentrations, or a significant reduction in titer, in all twelve specimens studied. These results give rise to at least two possible interpretations: (1) antibodies to native DNA are unusual with respect to the ease with which their binding to antigen may be inhibited by these three chemically unrelated compounds, and (2) steroid receptors are somehow involved in the binding of these antibodies to native DNA.
Animals↗
Urinary immune complexes in patients with glomerular diseases. Their possible diagnostic implications.
Urine specimens from 65 patients with glomerular disease and from 62 controls were tested for the presence of immune complexes by agarose gel zone electrophoresis. Urinary immune complexes (UICs) were found in 18% of patients, correlating with the simultaneous occurrence of serum immune complexes and depending differentially on the histologic form of glomerular disorder. The UICs were found preponderantly in patients with severe crescentic glomerulonephritis, who had "gaps" in the glomerular basement membrane; in patients with epimembranous electron-dense deposits; and in patients with membrano-proliferative glomerulonephritis. The UICs were detected in no patients with focal glomerular sclerosis or mesangial proliferative glomerulonephritis and in only one of 23 patients with minimal-change disease. None of 62 controls had UICs. Passage of immune complexes through filtering structures of the kidneys may be a consequence of their focal or diffuse damage. Detection of UICs may provide a noninvasive means of assessing the extent of tissue injury in patients with glomerular disorders.
Antigen-Antibody Complex↗
Trimethoprim-sulfadiazine in the horse: serum, synovial, peritoneal, and urine concentrations after single-dose intravenous administration.
Six healthy adult mares were given a single IV injection of trimethoprim (TMP)-sulfadiazine (SDZ) at a dosage rate of 2.5 mg of TMP/kg of body weight and 12.5 mg of SDZ/kg. Serum, synovial, peritoneal, and urine TMP-SDZ concentrations were measured serially over a 48-hour period. The highest measured mean concentrations of TMP and SDZ were found in the first (0.5 hour) sample of serum, synovial fluid, and peritoneal fluid. The mean peak concentrations of TMP and SDZ averaged 4.37 micrograms/ml and 21.81 micrograms/ml for serum, 2.95 micrograms/ml and 15.31 micrograms/ml for synovial fluid, and 3.88 micrograms/ml and 19.52 micrograms/ml for peritoneal fluid, respectively. Urine concentrations of the drugs were relatively high and peaked early. The elimination rate for TMP and SDZ averaged 0.41 and 0.26 hour-1, while the elimination half-life was 1.91 and 2.71 hours, respectively, and the volume of distribution averaged 0.59 and 0.52 L/kg, respectively.
Animals↗
Immune complexes in progressive systemic sclerosis (scleroderma).
Serum immune complexes were measured in 92 patients with progressive systemic sclerosis, and elevated levels were found as follows: Raji cell assay 72% (59% after pronase treatment of Raji cell), agarose gel electrophoresis 52%, and C1q binding 24%. Forty-three (47%) had abnormal results on two or more of these tests, but only 17 (18%) had normal results by all three assays. Computer-assisted analysis of immune complex results and extensive clinical and laboratory data compiled on these patients revealed that the patients with abnormal Raji cell assays more often had diffuse scleroderma, tendon friction rubs, and positive serum antinuclear antibody tests than did patients with negative results on Raji cell assays. Individuals with immune complexes detected by C1q binding had evidence of pulmonary involvement and positive serum rheumatoid factor more frequently than did patients whose C1q tests were negative.
Adolescent↗
Prostaglandin-mediated inhibition of lymphokine secretion in normal individuals and patients with progressive systemic sclerosis (scleroderma, PSS).
The sensitivity of peripheral blood lymphocytes to E-type prostaglandin-mediated inhibition of lymphokine secretion was examined in 3 groups of individuals; normal controls, hospitalized patients, and patients with progressive systemic sclerosis (PSS, scleroderma). Leukocytes were stimulated by a polyclonal T-cell activator, phytohemagglutinin, and the release of the lymphokine, leukocyte migration inhibitory factor (LIF), was measured in the presence or absence of exogenous PGE2 using a direct agarose droplet migration inhibition technique. Leukocytes of scleroderma patients were found to be hyporesponsive to E-type prostaglandin (i.e., lymphokine secretion by these cells was not inhibited at concentrations of PGE2 between 2.8 X 10(-8) and 2.8 X 10(-5) M). In addition, a marked sex difference in PGE responsiveness was found to exist among normal controls, whereby females were hyporesponsive during the latter half of the menstrual cycle. It is possible that this deficit may facilitate, in part, the development of connective tissue diseases in women of childbearing age. The inability to suppress lymphokine production and arrest persistent immune reactivity, coupled with the known ability of lymphokines to augment fibroblast collagen production, offers a a reasonable explanation for the accumulation of tissue collagen in scleroderma.
Adult↗
Cerebrospinal fluid immune complexes in systemic lupus erythematosus involving the central nervous system.
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Adrenal Cortex Hormones↗
Gentamicin sulfate in the horse: serum, synovial, peritoneal, and urine concentrations after single dose intramuscular administration.
Ten healthy adult mares were given a single intramuscular dose (2.2 mg/kg) of gentamicin sulfate. Over a 48-h period, gentamicin concentrations were measured serially in the serum of all ten mares and in synovial fluid, peritoneal fluid, and urine of six of the mares. The mean peak serum gentamicin concentration was 5.73 micrograms/ml at 1 h. Gentamicin was detected in synovial fluid and peritoneal fluid, with mean peak gentamicin concentrations of 2.41 micrograms/ml and 3.92 micrograms/ml, respectively, observed at 2 h. These concentrations declined in parallel with serum concentrations and were not measurable at 48 h. Urine gentamicin concentration was relatively high, with a mean peak concentration of 424.9 micrograms/ml at 1 h after drug administration.
Animals↗