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Biomedical subjects

J E Balow

Publications and source records attributed to J E Balow.

At least 91 records · Page 5Linked to original sources
PubMed1987

In vitro generated human monoclonal trinitrophenyl-specific B cell lines. Evidence that human and murine anti-trinitrophenyl monoclonal antibodies cross-react with Escherichia coli beta-galactosidase.

Stable human antigen-specific monoclonal B cell lines were established without prior in vivo immunization. This was accomplished by expanding the anti-trinitrophenyl (TNP) B cells in vitro with the antigen TNP-Brucella abortus and then immortalizing them with Epstein-Barr virus. Five anti-TNP clones were selected by sequential limiting dilution. All five anti-TNP clones secreted IgM kappa antibodies. When tested against a panel of self and environmental antigens, all five anti-TNP clones exhibited cross-reactivity with an Escherichia coli-derived beta-galactosidase. To determine whether this was a more general phenomenon, a panel of murine monoclonals were tested and found to bind to beta-galactosidase. It is therefore possible that human and murine anti-TNP beta cell responses reflect reactivity against an environmental antigen, namely an epitope present on E. coli-derived beta-galactosidase. This approach of expanding human antigen-specific B cells by antigen stimulation in vitro, with a T-independent hapten-carrier conjugate before Epstein-Barr virus transformation, may prove useful in the development of human monoclonals for therapeutic purposes.

Animals↗
PubMed1987

NIH conference. Lupus nephritis.

Nephritis has long been considered one of the most ominous components of systemic lupus erythematosus. Accumulations of immune complexes and lymphoid cells in several locations within the kidney are the best-described elements of lupus nephritis. The extreme diversity of the renal changes indicates that many variables are likely to be involved. Inbred strains of lupus-prone mice have provided homogeneous subjects for study of pathogenesis and response to treatment. Comparable grouping of lupus nephritis in humans according to unique or dominant pathogenetic mechanisms is imprecise and limited by insufficient knowledge of the primary stimulus for the disease. Treatment is also imperfect and, at times, hazardous. Certain regimens incorporating cytotoxic drugs provide a significant therapeutic advantage over corticosteroids alone in the management of this disease.

Adult↗
PubMed1987

Studies of immunosuppressive drugs in the treatment of lupus nephritis.

Long-term, controlled trials to evaluate the efficacy and toxicities of immunosuppressive drug therapies compared to treatment with corticosteroids alone in the management of patients with lupus nephritis have been performed. The studies demonstrate that immunosuppressive drug regimens, particularly intravenous cyclophosphamide, reduce the likelihood of end-stage renal failure. However, toxicities such as herpes zoster and ovarian failure were found to be increased in patients with cyclophosphamide.

Child↗
PubMed1986

Production of nephritic factor of the alternative complement pathway by Epstein Barr virus-transformed B cell lines derived from a patient with membranoproliferative glomerulonephritis.

Nephritic factor of the alternative complement pathway (C3NeF) is an IgG autoantibody which binds to and stabilizes the C3 convertase (C3bBb) enzyme, and which has been detected mainly in sera from patients with membranoproliferative glomerulonephritis (MPGN) and partial lipodystrophy. To study the production of C3NeF, mononuclear cells isolated from the peripheral blood of patients with MPGN and C3NeF activity in their sera were infected with Epstein Barr virus (EBV) to establish active B lymphocyte cell lines. By using a modified C3NeF screening assay, we detected C3NeF activity in the supernatant of a B cell line derived from a patient with MPGN Type II, but in none of the supernatants of B cell lines derived from normal individuals. C3NeF-positive supernatants were investigated for their ability to conserve classical or alternative pathway C3 convertase activity by using EAC3bBb and EAC4b2a stabilization assays. C3NeF-positive supernatants stabilized the C3bBb convertase activity, but not the C4b2a convertase activity. Studies of the supernatants, using anti-human IgG affinity columns, showed that the C3NeF activity was in the IgG fraction; furthermore, C3NeF antibody agglutinated sheep erythrocytes coated with C3bBb, but not with C3b alone. On gel electrophoresis, both heavy and light chains of the C3NeF were comparable in size to that of normal human IgG molecules. We conclude that C3NeF, produced in vitro by EBV-transformed B cell lines derived from a patient with MPGN Type II, is functionally identical to the conventional C3NeF in serum. In vitro preparation of homogeneous NeF(s) should greatly facilitate the studies of the role of these autoantibodies in complement dysmetabolism.

B-Lymphocytes↗
PubMed1986

Renal histopathologic alterations in patients treated with cyclosporine for uveitis.

To evaluate abnormalities of renal morphology associated with long-term cyclosporine therapy, we obtained percutaneous renal biopsy specimens from 17 patients who had been treated for autoimmune uveitis with cyclosporine for an average of two years. For comparison, we also analyzed renal biopsy specimens from patients with idiopathic hematuria who had not received cyclosporine. The atrophic and sclerosing glomerular and tubulointerstitial lesions in the specimens were assessed to derive a chronicity index. The specimens from the patients treated with cyclosporine showed a significantly higher chronicity index than those from the controls (P less than 0.00005). All patients who had received cyclosporine had interstitial fibrosis, tubular atrophy, or both. A good functional predictor of the abnormalities in renal morphology was the length of time that a patient's serum creatinine had exceeded the base-line value by more than 50 percent. Chronic pathologic alterations were seen even in patients who had normal renal function at the time of the biopsy. In conjunction with sequential measurements of renal function, renal biopsy may have an important role in defining the type and degree of nephrotoxicity that can develop in patients receiving long-term cyclosporine therapy for autoimmune disease.

Adolescent↗
PubMed1986

Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs.

We evaluated renal function in 107 patients with active lupus nephritis who participated in long-term randomized therapeutic trials (median follow-up, seven years). For patients taking oral prednisone alone, the probability of renal failure began to increase substantially after five years of observation. Renal function was better preserved in patients who received various cytotoxic-drug therapies, but the difference was statistically significant only for intravenous cyclophosphamide plus low-dose prednisone as compared with high-dose prednisone alone (P = 0.027). The advantage of treatment with intravenous cyclophosphamide over oral prednisone alone was particularly apparent in the high-risk subgroup of patients who had chronic histologic changes on renal biopsy at study entry. Patients treated with intravenous cyclophosphamide have not experienced hemorrhagic cystitis, cancer, or a disproportionate number of major infections. We conclude that, as compared with high-dose oral prednisone alone, treatment of lupus glomerulonephritis with intravenous cyclophosphamide reduces the risk of end-stage renal failure with few serious complications.

Administration, Oral↗
PubMed1986

Type C retroviruses of the human T cell leukemia family are not evident in patients with systemic lupus erythematosus.

Type C retroviruses of the human T cell leukemia virus (HTLV) family have been implicated in immune aberrations observed in patients with leukemias, lymphomas, and the acquired immune deficiency syndrome. We have investigated whether retroviruses of the HTLV family are involved in the etiopathogenesis of systemic lupus erythematosus (SLE) by using 1) an immunoenzymatic assay to measure antibodies to HTLV-I and HTLV-III proteins in the sera of 30 patients with SLE, and 2) nucleic acid hybridization techniques (Southern transfer) to detect proviral sequences of HTLV-I, HTLV-II, and HTLV-III in DNA extracted from peripheral blood mononuclear cells of 10 of these patients. Sera from 20 normal individuals served as controls. None of the 30 sera from SLE patients or the 20 sera from normal controls had any detectable antibodies to HTLV-I or HTLV-III. Nucleic acid hybridization studies also failed to detect any HTLV proviral sequences. These results suggest that viruses of the HTLV family do not participate in the etiopathogenesis of SLE.

Antibodies, Viral↗
PubMed1986

Deficient gamma-interferon production in patients with systemic lupus erythematosus.

We examined the ability of peripheral mononuclear cells (MNC) from patients with systemic lupus erythematosus (SLE) to produce gamma-interferon (gamma-IFN) in vitro. MNC from patients with SLE produced varying amounts of gamma-IFN upon mitogenic stimulation. However, they produced distinctly decreased amounts of gamma-IFN upon in vitro stimulation with interleukin-2 (IL-2). Deficient production seemed to be primary, rather than secondary to either excessive monocytic suppression or failure of IL-2 to bind to the MNC surface membranes. gamma-IFN-specific RNA transcription, as determined by slot-blot analysis, was severely decreased in MNC that had been stimulated with phytohemagglutinin or IL-2. These findings suggest that MNC of patients with SLE have defects in the IL-2 signal transduction which is required for production of gamma-IFN.

Humans↗
PubMed1986

Development of hypogammaglobulinemia in a patient with systemic lupus erythematosus.

This report describes a young girl in whom systemic lupus erythematosus (SLE) with normogammaglobulinemia but high serum DNA binding developed at age 10. She was subsequently treated with prednisone and intermittent cyclophosphamide for six years, and severe hypogammaglobulinemia associated with recurrent infections developed; disease remained active and serum DNA binding high. The possible contribution of treatment with cyclophosphamide to the development of hypogammaglobulinemia is discussed.

Agammaglobulinemia↗
PubMed1986

Immunoregulatory disorders associated with hereditary angioedema. I. Clinical manifestations of autoimmune disease.

Occasional reports have appeared linking hereditary angioedema (HAE) with autoimmune diseases. We have systematically evaluated 157 patients for manifestations of autoimmunity. Nineteen of these patients (12%) had clinical immunoregulatory diseases including glomerulonephritis (five patients), Sjögren's syndrome (three), inflammatory bowel disease (three), thyroiditis (two), systemic lupus erythematosus (one), drug-induced lupus (one), rheumatoid arthritis (one), juvenile rheumatoid arthritis with IgA deficiency (one), incipient pernicious anemia (one), and sicca syndrome (one). All eight patients with HAE who developed an autoimmune disease with a known human histocompatibility antigen association developed a disease associated with their histocompatibility antigen haplotype (p = 0.014). Although only four patients developed Sjögren's syndrome or sicca syndrome, an additional nine manifested part of the sicca complex. We also found patients with HAE with features suggestive of an immune-based abnormality. These features included idiopathic pancreatitis (three patients), Raynaud's disease (two), partial lipodystrophy (one), chronic chorioretinitis (one), and alopecia universalis (one).

Adolescent↗
PubMed1986

Immunoregulatory disorders associated with hereditary angioedema. II. Serologic and cellular abnormalities.

Hereditary angioedema is defined biochemically by a deficiency in the functional activity of the inhibitor of Cl, Cl esterase inhibitor (Cl INH). Deficiency of this regulator of the early classic pathway of complement results in chronic activation of this cascade with a resultant deficiency of C4 and C2. Ninety-seven patients with either complicated (associated with autoimmune disorders) or uncomplicated hereditary angioedema were evaluated for laboratory evidence of immunoregulatory defects. Specific cellular and humoral abnormalities were found and included increased mean total lymphocyte counts, increased mean Leu 4+ (total) and Leu 3+ (helper) T cells, an increased mean Leu 3/Leu 2 (helper/suppressor T cell) ratio, polyclonal B cell activation, and evidence of circulating immune complexes. C4 functional titers were negatively correlated with percent Leu 3+ cells and absolute Leu 3+ cell numbers. We failed to detect any evidence of immune deficiency in this population, and yet a statistically significant number of patients demonstrated elevated levels of antibodies to Epstein-Barr virus antigens when patients were compared to a control group. Thus, early classic complement pathway activation and/or partial complement component deficiency may effect T cell subpopulations and B cell activation. However, additional predisposing factors (e.g., genetic or viral) appear necessary for the development of a particular autoimmune disease in hypocomplementemic patients.

Adolescent↗
PubMed1986

Decreased interleukin 2 inhibitor in sera of patients with autoimmune disorders.

The lymphokine, interleukin 2 (IL-2), is an important modulator of cell-mediated immune (CMI) responses. We report here the detection of an inhibitor of IL-2 in normal sera by measuring the inhibition of thymidine incorporation in IL-2 dependent murine CTLL cells. The inhibitor, partially purified by Sephacryl S-200 gel filtration, eluted with the 60,000-70,000 mol. wt fraction. The factor was destroyed at 56 degrees C for 30 min and did not bind to Protein A Sepharose, suggesting that it is not an immunoglobulin G. Of 26 normal sera tested, 23 had significant levels of the inhibitor. Since connective tissue diseases are often associated with deficient CMI responses, we examined the levels of IL-2 inhibitor in 26 systemic lupus erythematosus (SLE) and 22 rheumatoid arthritis (RA) patients. Only 8 SLE and 12 RA patients had normal levels of the inhibitor. Of the 18 SLE patients with low or undetectable levels, 15 had clinically defined active disease and of the eight with normal levels, three had active disease. The decrease in the IL-2 inhibitor level did not correlate either with steroid or cyclophosphamide treatment or with serum levels of DNA binding and C3. These data suggest that the function of the inhibitor is to control IL-2 activity under normal conditions. Decreased levels of the IL-2 inhibitor in these patients might be explained either as a reduced requirement of this regulatory protein secondary to decreased IL-2 production or a defect of the cells responsible for the production of both IL-2 and its inhibitor.

Arthritis, Rheumatoid↗
PubMed1985

Interleukin-2 restores the depressed allogeneic cell-mediated lympholysis and natural killer cell activity in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is characterized by a variety of profound T-cell abnormalities among which are decreased cytotoxic capacity measured by allogeneic cell-mediated lympholysis (CML), natural killer cell (NK) activity, and decreased lymphokine production. In a group of 13 patients with active SLE, allogeneic CML, tested by a 4-hr 51Cr-release assay, was 18.2 +/- 2.7% while in the group of normal individuals CML was 41.2 +/- 2.7%. If optimal doses of affinity-purified interleukin-2 (IL-2) were present during the mixed lymphocyte culture, the CML of SLE patients was increased to normal levels (40.4 +/- 4.0%). In contrast, interferon-alpha (IFN-alpha) increased (but not significantly) the levels of CML. Mixed lymphocyte reaction, tested by tritiated thymidine incorporation, was also decreased in the group of patients (14,820 +/- 815 cpm vs 28,972 +/- 5880 cpm in normals) and it was increased to normal levels if IL-2, but not IFN-alpha was added to the cultures. NK activity was decreased in the group of patients tested by 51Cr-release assay, harvested at 6 and 18 hr. IL-2 increased the NK activity up to normal levels, while IFN-alpha was only partially efficacious. These results demonstrate that IL-2, but not IFN-alpha, can potentiate or even fully restore the deficient cytotoxic effector function of peripheral mononuclear cells in patients with SLE.

Cytotoxicity, Immunologic↗
PubMed1985

Therapy of anti-glomerular basement membrane antibody disease: analysis of prognostic significance of clinical, pathologic and treatment factors.

We have compared the effect of therapy with immunosuppression alone to immunosuppression plus plasma exchange on the clinical course and rate of disappearance of antibody in 17 patients with anti-glomerular basement membrane (anti-GBM) antibody-induced renal disease. Patients receiving immunosuppression (n = 9) and those receiving plasma exchange (n = 8) were similar in terms of entry clinical characteristics, pulmonary manifestations and complications associated with therapy. Rate of disappearance of anti-GBM antibody as estimated from serial estimates of antibody binding was significantly more rapid in patients receiving plasma exchange, and mean serum creatinine in these patients at end of therapy was half that of the patients receiving immunosuppression alone. Analysis of clinical and pathologic values at study entry, however, indicated that the percent of crescents on initial renal biopsy and entry serum creatinine correlated better with outcome than did therapeutic modality. Thus, though plasma exchange may offer some advantage over immunosuppression alone in the treatment of this disease, degree of pathologic involvement appears to be the major factor affecting outcome. Patients with low cresents (less than 30%) and well preserved function did well with either treatment, while patients with severe crescentic involvement and impaired glomerular filtration rate did poorly.

Adolescent↗