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J E Balow

Publications and source records attributed to J E Balow.

At least 73 records · Page 4Linked to original sources
PubMed1990

The CR2 receptor (CD21) shows increased expression in the more differentiated cells of an antigen-specific B cell line.

The complement receptor 2 (CR2; CD21), a 145,000 MW glycoprotein, has been useful as a marker of B lymphocyte maturation. It is expressed on the 1:13 monoclonal, EBV-transformed, B cell line which produces TNP-specific IgM-kappa and displays an in vitro capacity for differentiation. The line expresses the CD20+CD21+ phenotype. We studied whether CR2 receptor surface expression varied in relation to the cell cycle or state of differentiation in the 1:13 line. High CD21 and IgM expression occurred in the G1 phase of the cell cycle. In contrast to CD21, there were no distinctly brighter subpopulations of CD20 positive cells in the G1, S, or G2M compartments of the cell cycle. When sorted according to size, smaller cells were predominantly in G1, whereas a greater proportion of the larger cells were in the G2M phase of the cell cycle. The smaller 1:13 cells expressed more CD21 surface antigen and IgM than the larger cells. Cells which formed stable rosettes with TNP-SRBC expressed more surface IgM and CD21 antigen than nonrosetting cells. We have previously shown that the TNP-SRBC rosetting cells were more differentiated, resided in G1, and secreted more immunoglobulin than the nonrosetting cells. Thus increased CR2 expression occurred in the more differentiated cells of this human monoclonal B cell line.

Antigens, CD↗
PubMed1990

Lymphocyte activation markers in idiopathic myositis: changes with disease activity and differences among clinical and autoantibody subgroups.

We studied the immunologic correlates of disease activity and differences among subgroups of patients with idiopathic inflammatory myopathy by analysing phenotypic and activation marker expression on peripheral blood mononuclear cells (PBMC). Compared with controls, myositis patients with clinically active disease (n = 51) had significantly lower proportions of CD8+ cells and higher proportions of PBMC that expressed DR, CD3- DR, CD14- DR, interleukin-2 receptors, and the late T cell activation markers CD26 and TLiSA1. TLiSA1 expression, a marker for cytotoxic differentiation, correlated significantly with both clinical activity indices and serum levels of muscle-associated enzymes. In serial studies of seven patients, the proportion of PBMC expressing MHC class II antigen and late T cell activation markers decreased as myositis disease activity decreased, independent of type of therapy. Among the clinical subgroups, polymyositis (n = 21) and inclusion body myositis (n = 11) were virtually indistinguishable; dermatomyositis patients (n = 19) showed decreased proportions of CD3+DR+ and TLiSA1+ cells, and increased proportions of CD20+ and CD20+DR+ cells compared with the other two groups. Patients with autoantibodies to histidyl-tRNA synthetase (Jo-1 antigen, n = 11) had significantly lower proportions of CD3+ and CD4+ cells, lower CD4/CD8 ratios, and higher proportions of CD+ cells expressing CD20, compared with patients without anti-Jo-1 antibodies. These findings support the concept that activated lymphocytes, especially cells undergoing anamnestic responses and cytotoxic differentiation, are important in the pathogenesis of idiopathic myositis. Moreover, taken together with other studies, these data suggest that groups of patients segregated by clinical or autoantibody status have different mechanisms of systemic immune activation and immunopathology.

Adult↗
PubMed1990

Acute transverse myelitis in systemic lupus erythematosus: magnetic resonance imaging and review of the literature.

We describe a patient with systemic lupus erythematosus (SLE) who presented with acute transverse myelitis. Magnetic resonance imaging (MRI) of the cervical spine demonstrated increased signal intensity and diffuse edema in the cervical cord. The patient had low titer of IgG antiphospholipid antibodies and hypocomplementemia. Cerebrospinal fluid analysis showed pleocytosis, increased protein and decreased glucose. Clinical improvement of the neurologic impairment was noted after high dose corticosteroids and intravenous bolus cyclophosphamide. A repeat MRI 12 days after the treatment was normal. MRI of the spine can be useful in the diagnosis and followup of patients with SLE presenting with an acute myelopathic syndrome. Early aggressive treatment may contribute to complete recovery of these patients.

Adolescent↗
PubMed1989

High-affinity antibodies to ssDNA are produced by CD-B cells in systemic lupus erythematosus patients.

It was previously shown that human CD5+B cells are committed to the production of polyreactive "autoantibodies" that bind different self-Ag, including ssDNA, IgG Fc fragment, thyroglobulin, and insulin, as well as exogenous Ag, e.g., tetanus toxoid and other bacterial components. To define the contribution of the CD5+B cell subset to the production of antibodies to ssDNA in SLE, we quantitated, purified, and functionally characterized circulating CD5+ and CD5-B cells in patients and in healthy subjects. We found that in SLE patients circulating CD5+B cells were not increased in number, and both CD5+ and C5-B cells spontaneously secreted antibodies to ssDNA. Studies of the mAb we generated using CD5+ and CD5-B cells revealed that two types of antibody to ssDNA are produced in SLE. The first type, of the IgM class, is produced mainly by CD5+B cells and displays a moderate affinity for ssDNA (Kd, 10(-6) to 10(-7) mol/liter) and is polyreactive, not dissimilar to the autoantibodies inducible in the normal human B cell repertoire by polyclonal activation. The second type, mostly of the IgG and IgA class, is produced mainly by CD5-B cells and displays a higher affinity (Kd, 10(-8) mol/liter) for and reacts only with ssDNA. The functional features of the high affinity anti-ssDNA antibodies and the phenotype of their producing B cells mimic those characteristic of a "mature" Ag-driven response, such as that to tetanus toxoid in tetanus toxoid-vaccinated subjects.

Adult↗
PubMed1989

Human polyclonal and monoclonal IgG and IgM complement 3 nephritic factors: evidence for idiotypic commonality.

Complement 3 nephritic factors (C3NeF) were isolated from the sera of patients with membranoproliferative glomerulonephritis (MPGN) and the supernatants of pokeweed mitogen-stimulated mononuclear cells from patients with MPGN. Three human monoclonal C3NeF antibodies (two IgGs, CK and PH, and one IgM, K3C4) were established. Using an exhaustive series of affinity columns, we isolated anti-C3NeF idiotypic antibodies (anti-IdNeF) (three from normal and two from patient sera). Anti-IdNeF preparations bound to F(ab')2-NeF and prevented its ability to stabilize C3bBb convertase. We have used the above reagents to address questions on the genesis and the diversity of C3NeF antibodies. The following results were obtained: All anti-IdNeF preparations bound to C3NeF isolated from patient sera, cell culture supernatants, and IgG and IgM monoclonal C3NeF. None of the monoclonal C3NeF bound to an extensive battery of common antigens, including Fc portion of IgG, TNP, beta-galactosidase, DNA, and bacterial products. These data indicate that C3NeF express one common idiotype and that these antibodies are not raised in response to an obvious antigen.

Antibodies, Monoclonal↗
PubMed1989

Transcriptional and post-transcriptional mechanisms are responsible for the increased expression of c-myc protooncogene in lymphocytes from patients with systemic lupus erythematosus.

Peripheral blood mononuclear cells (MNC) of patients with systemic lupus erythematosus (SLE) have increased expression of the c-myc protooncogene. The factors which are responsible for the accumulation of c-myc mRNA levels in SLE MNC, however, have not been determined. We have investigated the steady-state mRNA accumulation, nuclear transcription rate, rate of mRNA degradation as well as methylation status for the c-myc protooncogene in patients with SLE. Increased transcription rate of c-myc protooncogene and slow degradation rate of c-myc mRNA both appear to contribute to the accumulation of c-myc RNA in peripheral blood MNC of patients with SLE. Site-specific methylation of the human c-myc protooncogene in patients with SLE does not differ from that of normal controls. These findings provide evidence for both transcriptional and post-transcriptional alterations of c-myc protooncogene expression in human SLE.

Cell Nucleus↗
PubMed1989

Evolution of ciclosporin nephrotoxicity in patients treated for autoimmune uveitis.

Among 73 patients treated with ciclosporin (CS) for autoimmune uveitis, a 50% elevation of serum creatinine was observed in 37% within 3 months of starting CS and in 25% after more than 6 months of relatively uncomplicated therapy. Sequential renal function and histologic evaluations were performed in 17 patients to further characterize the nephrotoxic effects of long-term CS therapy. Inulin clearance remained essentially unchanged in 12 patients despite CS dosage reductions in the majority. In 2 such patients, repeat renal biopsy specimens revealed evidence of progressive irreversible kidney injury even though renal function was stable. Inulin clearance decreased substantially in 3 patients; in 1 case a follow-up renal biopsy showed increased severity of chronic histologic change. For 2 patients, the inulin clearance more than doubled after CS dosage reduction; and in 1 of those cases, repeat renal biopsy showed no evidence of progressive renal scarring. Overall, the morphologic attributes of irreversible kidney injury (designated by a chronicity index including glomerular sclerosis, tubular atrophy and interstitial fibrosis) were increased in 3 of 6 follow-up renal biopsy specimens. Histologic alterations of renal arterioles, including hyaline change, were observed in all CS-treated patients. The hyaline change of arterioles was either extensive in the first renal biopsy specimen or became extensive in the second biopsy in the 3 cases manifesting an increased chronicity index on the follow-up renal biopsy. Thus, parenchymal injury can progress in some cases despite CS dosage reduction and stable renal function; renal arteriolar histologic change is a prominent finding in these patients. Patients that exhibit a substantial improvement in renal function after dosage reduction may experience a more favorable course.

Autoimmune Diseases↗
PubMed1989

Morphologic differences between polyarteritis and Wegener's granulomatosis using light, electron and immunohistochemical techniques.

The differential diagnosis of renal biopsies of patients with polyarteritis nodosa (PAN) versus those with Wegener's granulomatosis (WG) is difficult because in both the morphologic expression is a focal proliferating and necrotizing glomerulonephritis (GN) with crescents. Twenty-nine biopsies of PAN and 29 of WG were studied by light, electron microscopy and immunohistochemistry. Whereas in PAN the dominent feature is severe focal fibrinoid necrosis of glomerular tufts, WG is characterized by destructive extracapillary GN with capsular breaks and periglomerulitis leading to complete glomerular destruction and replacement by a localized inflammatory exudate in the form of a granuloma. In PAN necrotizing arteritis is common (19 of 29), whereas only 1 of 29 cases of WG showed arteritis. Depending on the stage of the disease, various types of hematogenous cells can be seen in both. In general, the dominent cell type in PAN is polymorphonuclear cells (PMNs) with or without eosinophils, whereas in WG mononuclear cells dominate the picture. Monocytes and macrophages, including giant cells in the crescents, periglomerular infiltrates, and in the granulomas are seen, whereas in the interstitium, plasma cells predominate. The histologic ultrastructural and immunohistochemical findings in both groups will be discussed.

Adolescent↗
PubMed1989

IgA rheumatoid factor and IgA containing immune complexes in primary Sjögren's syndrome.

IgA rheumatoid factor (RF) and immune complexes containing IgA-IgG, C3-IgA, and C3-IgG from sera of patients with primary Sjögren's syndrome and controls were quantified by ELISA. Salivary tissue obtained from patients at the same time as serum was scored to simultaneously reflect lymphoplasmocytic infiltrate and fibrosis. Patients had significantly increased amounts of IgA RF and all complexes when compared to controls (p less than 0.0005). IgA-IgG complexes, thought to be IgG-IgA RF complexes, were inversely correlated to tissue pathology (p less than 0.001) and peripheral white blood cell counts. Additionally, IgA RF was inversely correlated to stimulated parotid flow. This suggests immune complex formation precedes tissue destruction or is associated with less destructive pathology in primary Sjögren's syndrome.

Adult↗
PubMed1988

Acyclovir-induced renal failure. Clinical course and histology.

Four patients with a chronic fatigue syndrome experienced five episodes of acute renal insufficiency associated with high-dose (500 mg/m2) intravenous acyclovir administered intravenously as one-hour infusions. Nephrotoxicity developed despite precautions to avoid volume contraction. Examination of the urinary sediment of three patients by polarizing microscopy showed birefringent needle-shaped crystals within leukocytes. In the most severely affected patient, a serum creatinine concentration of 8.6 mg/dl developed and the patient underwent percutaneous renal biopsy that revealed foci of interstitial inflammation without tubular necrosis. Urine, blood, and renal tissue levels of acyclovir were high. One patient was rechallenged with low-dose intravenous acyclovir and the four patients later received oral acyclovir, all without adverse effect. The combined data from these patients support crystalluria and obstructive nephropathy as a mechanism of acyclovir-induced renal failure in humans. This experience emphasizes the importance of maintaining adequate hydration during high-dose acyclovir therapy.

Acute Kidney Injury↗
PubMed1988

Mood effects of alternate-day corticosteroid therapy in patients with systemic lupus erythematosus.

Mood and cognition were assessed on consecutive days in 18 female patients with systemic lupus erythematosus on alternate-day corticosteroid therapy. No overall differences in mood and cognition were observed between the on- and off-medication days. However, 10 patients showed marked worsening or improvement of either depression or anxiety on their off-medication day. Two weeks of prospective behavioral ratings confirmed the observed mood changes in several patients. The clinical and theoretical implications of these findings are discussed.

Adult↗
PubMed1988

Model for studying virus attachment: identification and quantitation of Epstein-Barr virus-binding cells by using biotinylated virus in flow cytometry.

Epstein-Barr virus (EBV) was purified and biotinylated without significant loss of its cell-transforming activity. The use of biotinylated virus in conjunction with antibodies specific for selected cell surface molecules and flow cytometric analysis allowed for the positive identification of the virus-binding lymphocytes among a heterogeneous mononuclear cell population. Biotinylated EBV efficiently bound to all B lymphocytes, including those bearing surface mu, delta, gamma, and alpha immunoglobulin heavy chains or the surface CD5 (Leu-1) marker, but not to T lymphocytes, natural killer cells, or monocytes. By using biotinylated EBV and specific monoclonal antibodies in competitive inhibition experiments, it was also found that the virus attaches to an epitope on the CR2 molecule (the receptor for C3d and EBV), which is close to or identical with the one recognized by OKB7 monoclonal antibody, and that cell surface structures other than CR2 cannot mediate attachment of EBV. Moreover, studies on the binding of the virus to induced B lymphocytes (cells in S through G2 phase), and this was associated with the disappearance of the surface CR2 molecule and the inability of the virus to attach to these cells. The approach described here should be useful in studying the attachment of other viruses, identifying the specific cell types involved, and analyzing the effect of the cell cycle on virus binding.

Antibodies, Monoclonal↗
PubMed1988

Renal disease in systemic lupus erythematosus.

Lupus nephritis is the archetype of diseases caused by the deposition of immune complexes. The characteristics which render only a portion of circulating immune complexes nephritogenic are not well delineated, but cat-ionic charge of antigen and/or antibody may contribute. Lupus nephritis is characterized by extreme diversity of clinical manifestations and pathologic features. Scrupulous monitoring of urinary sediment and renal function tests is necessary to identify renal involvement in a phase which is amenable to therapeutic intervention. Evaluation of renal biopsies also assists in development of indications for therapy. The pathology of lupus nephritis is classified primarily as mesangial, focal proliferative, diffuse proliferative, and membranous nephropathy. Indexes of activity and of chronicity provide a succinet description of the balance of reversible and irreversible disease. The activity index incorporates glomerular hypercellularity, karyorrhexis/fibrinoid necrosis, leucocyte exudation, hyaline thrombi, cellular crescents, and interstitial inflammation. The chronicity index incorporates glomerular sclerosis, fibrous crescents, tubular atrophy, and interstitial fibrosis. Delineation of the activity and chronicity indexes also facilitates the assessment of prognosis and the ordering of indications for therapy.

Humans↗
PubMed1988

Lupus nephritis: association between serology and renal biopsy measures.

The relationship between serologic tests and renal histologic change over time was examined in 55 patients with lupus nephritis. After a median interval of 40 months on various immunosuppressive drug regimens, C3 complement levels were improved in 78% of patients and anti-DNA levels were improved in 85%. Comparison of initial and followup renal pathology showed that the activity index of the biopsy improved in 82%, while the chronicity index worsened in 71% of patients. Normalization of C3, but not anti-DNA levels, was associated with a lowering of the activity index on repeat biopsy. Prolonged depression of serum C3 levels was associated with a trend (p = 0.066) towards worsening of the chronicity index, but the change in chronicity index showed no relationship to the duration of elevated anti-DNA. Our studies indicate that abnormal levels of C3 complement are predictive of the degree of persistently active glomerular disease, but that duration of abnormal C3 or anti-DNA are less consistent predictors of the acquisition of chronic, irreversible renal lesions.

Antibodies, Antinuclear↗