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J E Balow

Publications and source records attributed to J E Balow.

At least 37 records · Page 2Linked to original sources
PubMed1997

Construction of a 1-Mb restriction-mapped cosmid contig containing the candidate region for the familial Mediterranean fever locus (MEFV) on chromosome 16p 13.3.

In this paper we describe the assembly and restriction map of a 1.05-Mb cosmid contig spanning the candidate region for familial Mediterranean fever (FMF), a recessively inherited disorder of inflammation localized to 16p13.3. Using a combination of cosmid walking and screening for P1, PAC, BAC, and YAC clones, we have generated a contig of genomic clones spanning approximately 1050 kb that contains the FMF critical region. The map consists of 179 cosmid, 15 P1, 10 PAC, 3 BAC, and 17 YAC clones, anchored by 27 STS markers. Eight additional STSs have been developed from the approximately 700 kb immediately centromeric to this genomic region. Five of the 35 STSs are microsatellites that have not been previously reported. NotI and EcoRI mapping of the overlapping cosmids, hybridization of restriction fragments from cosmids to one another, and STS analyses have been used to validate the assembly of the contig. Our contig totally subsumes the 250-kb interval recently reported, by founder haplotype analysis, to contain the FMF gene. Thus, our high-resolution clone map provides an ideal resource for transcriptional mapping toward the eventual identification of this disease gene.

Base Sequence↗
PubMed1997

Ongoing immunologic activity after short courses of pulse cyclophosphamide in the NZB/W murine model of systemic lupus erythematosus.

OBJECTIVE: Short courses of intermittent pulse cyclophosphamide (CY) have mitigated ovarian toxicity but have also led to incomplete or unsustained remissions of active systemic lupus erythematosus (SLE) in many patients, prompting an evaluation of the immunologic effects of this regimen in the NZB/W female mouse (B/W) model of human SLE. METHODS: Phenotypic and functional characteristics of spleen lymphocytes from B/W mice treated with short courses of intraperitoneal (i.p.) CY were compared to those from untreated control B/W mice. RESULTS: After a single dose (250 mg/kg) of i.p. CY, spleen lymphocyte subpopulations fell abruptly but recovered within 4 weeks. Four monthly doses of i.p. CY (starting at 5 months of age) led to a sustained reduction in spleen lymphocyte subpopulations and a parallel decrease in the number of spleen cells spontaneously secreting immunoglobulin and anti-DNA antibody to about 30% of the number seen in untreated control B/W mice. Lipopolysaccharide induced secretion of total IgG and IgG anti-DNA by cultured spleen cells was not diminished one month after the 4 month course of i.p. CY. CONCLUSION: The 4 month course of i.p. CY produced a marked reduction in the number of activated B cells producing autoantibody, but did not achieve sustained immunomodulation judged by the unaltered proportion of spleen B cells spontaneously secreting immunoglobulin and anti-DNA, as well as the response to polyclonal activators of B cells. These results suggest a continued susceptibility to flares of SLE activity after brief courses of intensive immunosuppressive therapy.

Adjuvants, Immunologic↗
PubMed1996

Glucocorticoids modulate CD28 mediated pathways for interleukin 2 production in human T cells: evidence for posttranscriptional regulation.

In T cells stimulated through the T cell receptor (TCR), both cyclosporine (CsA) and glucocorticoids (GC) inhibit the transcription of the IL-2 gene. In these cells costimulation via the CD28 cell surface molecule further increases the transcription of IL-2 and stabilizes its mRNA, resulting in a 20-30 fold induction in IL-2 production. This pathway is relatively resistant to the inhibitory effect of CsA. In this study, we asked whether GC interfere with CD28-mediated costimulatory signals for T cell activation. Primary human T cells or Jurkat T cells were stimulated with anti-CD28 and phorbol myristate acetate (PMA) in the presence of dexamethasone (Dex, 10(-10)-10(-5) M). Dex inhibited both the mRNA for IL-2 and IL-2 production in a dose-dependent fashion (minimum effective dose 10(-9) M). In similar experiments employing anti-CD3 mAb and PMA, a 7-20 fold higher concentration of Dex was required to obtain comparable inhibition. To determine if transcriptional modulation is occurring, Jurkat T cells were transfected with a plasmid containing the IL-2 promoter linked to the chloramphenicol acetyl transferase reporter gene. Following stimulation with ionomycin and PMA, high doses (10(-6) M) of Dex inhibited the activity of the IL-2 promoter (approximately 50% inhibition). However, in the presence of anti-CD28 mAb, this promoter became resistant to Dex (< or = 10% inhibition). These results suggest that GC inhibit accessory pathways for IL-2 production via CD28 by predominantly posttranscriptional mechanisms. Inhibition of the CD28 pathway may be an important mechanism for the T cell directed immunosuppressive effects of low-to-moderate doses of GC.

Antibodies↗
PubMed1996

Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial.

BACKGROUND: Uncertainty exists about the efficacy and toxicity of bolus therapy with methylprednisolone or of the combination of methylprednisolone and cyclophosphamide in the treatment of lupus nephritis. OBJECTIVE: To determine 1) whether intensive bolus therapy with methylprednisolone is an adequate substitute for bolus therapy with cyclophosphamide and 2) whether the combination of methylprednisolone and cyclophosphamide is superior to bolus therapy with methylprednisolone or cyclophosphamide alone. DESIGN: Randomized, controlled trial with at least 5 years of follow-up. SETTING: Government referral-based research hospital. PATIENTS: 82 patients with lupus nephritis who had 10 or more erythrocytes per high-power field, cellular casts, proteinuria (> 1 g of protein per day), and a renal biopsy specimen that showed proliferative nephritis. INTERVENTIONS: Bolus therapy with methylprednisolone (1 g/m2 body surface area), given monthly for at least 1 year; bolus therapy with cyclophosphamide (0.5 to 1.0 g/m2 body surface area), given monthly for 6 months and then quarterly; or bolus therapy with both methylprednisolone and cyclophosphamide. MEASUREMENTS: 1) Renal remission (defined as < 10 dysmorphic erythrocytes per high-power field, the absence of cellular casts, and excretion of < 1 g of protein per day without doubling of the serum creatinine level), 2) prevention of doubling of the serum creatinine level, and 3) prevention of renal failure requiring dialysis. RESULTS: Renal remission occurred in 17 of 20 patients in the combination therapy group (85%), 13 of 21 patients in the cyclophosphamide group (62%), and 7 of 24 patients in the methylprednisolone group (29%) (P < 0.001). Twenty-eight patients (43%) did not achieve renal remission. By life-table analysis, the likelihood of remission during the study period was greater in the combination therapy group than in the methylprednisolone group (P = 0.028). Combination therapy and cyclophosphamide therapy were not statistically different. Adverse events were amenorrhea (seen in 41% of the cyclophosphamide group, 43% of the combination therapy group, and 7.4% of the methylprednisolone group), cervical dysplasia (seen in 11% of the cyclophosphamide group. 7.1% of the combination therapy group, and 0% of the methylprednisolone group), avascular necrosis (seen in 11% of the cyclophosphamide group, 18% of the combination therapy group, and 22% of the methylprednisolone group), herpes zoster (seen in 15% of the cyclophosphamide group, 21% of the combination therapy group, and 3.7% of the methylprednisolone group) and at least one infection (seen in 26% of the cyclophosphamide group. 32% of the combination therapy group, and 7.4% of the methylprednisolone group). CONCLUSIONS: Monthly bolus therapy with methylprednisolone was less effective than monthly bolus therapy with cyclophosphamide. A trend toward greater efficacy with combination therapy was seen.

Adult↗
PubMed1996

Linkage disequilibrium mapping places the gene causing familial Mediterranean fever close to D16S246.

This report presents refined genetic mapping data for the gene causing familial Mediterranean fever (FMF), a recessively inherited disorder of inflammation. We sampled 65 Jewish, Armenian, and Arab families and typed them for eight markers from chromosome 16p. Using a new algorithm that permits multipoint calculations for a dense map of markers in consanguineous families, we obtained a maximal LOD score of 49.2 at a location 1.6 cM centromeric to D16S246. A specific haplotype at D16S283-D16S94-D16S246 was found in 76% of Moroccan and 32% of non-Moroccan Jewish carrier chromosomes, but this haplotype was not overrepresented in Armenian or Arab FMF carriers. Moreover, the 2.5-kb allele at D16S246 was significantly associated with FMF in Moroccan and non-Moroccan Jews but not in Armenians or Arabs. Since the Moroccan Jewish community represents a relatively recently established and genetically isolated founder population, we analyzed the Moroccan linkage-disequilibrium data by using Luria-Delbrück formulas and simulations based on a Poisson branching process. These methods place the FMF susceptibility gene within 0.305 cM of D16S246 (2-LOD-unit range 0.02-0.64 cM).

Algorithms↗
PubMed1996

Outpatient monthly oral bolus cyclophosphamide therapy in systemic lupus erythematosus.

OBJECTIVE: An open label study to determine the feasibility and acute toxicity of a 6 month course of outpatient intermittent bolus high dose oral cyclophosphamide in patients with active systemic lupus erythematosus (SLE). METHODS: Oral cyclophosphamide in a single dose of 0.5 to 1.0 g/m2 was given monthly for 6 consecutive months. Disease activity was monitored by quantitative assessments of urine sediment, 24h urine protein excretion, and the Systemic Lupus Activity Measure (SLAM). RESULTS: Twelve patients (11 with glomerulonephritis and one with thrombocytopenia) were studied. Improvements in SLAM scores, proteinuria, and urinary cellular casts were observed in the majority of the 9 patients with nephritis who completed the study. Adverse effects included mild nausea in most patients and intercurrent infections in 2 patients (herpes zoster, cellulitis, urinary tract infection). Three patients failed to complete the 6 month course of therapy because of treatment failure in the patient with thrombocytopenia, pregnancy, and severe vomiting, respectively. CONCLUSION: High dose pulse oral cyclophosphamide is an acceptable alternative for the aggressive outpatient management of selected patients with lupus nephritis.

Administration, Oral↗
PubMed1995

Regulation of transforming growth factor-beta 1 and its receptor by cyclosporine in human T lymphocytes.

Scarring, fibrosis, and immunosuppression occurs with chronic cyclosporine (CsA) administration. We postulated that CsA may induce transforming growth factor (TGF)-beta 1 secretion from human T lymphocytes, a cytokine with immunoregulatory effects that has been implicated in the pathogenesis of wound healing and scarring. TGF-beta 1 was measured in serum-free supernatants harvested from T lymphocytes stimulated in the presence of CsA by a specific sandwich ELISA. CsA (10-1000 ng/ml) enhanced TGF-beta 1 secretion by approximately 40-80% in a dose-dependent manner. Increased TGF-beta 1 secretion in the presence of CsA was accompanied by a 2- to 4-fold increase in TGF-beta 1 mRNA levels due to both enhancement of its nuclear transcription as well as prolongation of TGF-beta 1 mRNA half-life. To determine whether the increase in TGF-beta 1 secretion was also accompanied by a concomitant change in its receptor, TGF-beta 1 receptor expression was analyzed by cross-linking of radioiodinated TGF-beta 1. Unactivated T lymphocytes expressed both a 105-kDa and a 65-kDa TGF-beta receptor. Upon stimulation, a transient increase in receptor density was seen at 12 hr, followed by a decline at later time points. Cells treated with CsA exhibited at least 2-fold higher levels of TGF-beta receptors in a dose-dependent manner. Thus, CsA enhances the production of TGF-beta 1 protein as well as the expression of its receptor in activated T lymphocytes. Enhanced TGF-beta 1 production and binding may contribute to the immunosuppressive and fibrosis-promoting effects of CsA therapy.

Adult↗
PubMed1995

Glucocorticoid-mediated regulation of protein phosphorylation in primary human T cells. Evidence for induction of phosphatase activity.

Glucocorticoid hormones (GC) have profound effects on the development and homeostasis of the immune system. In this communication we present evidence that GC regulate Ca(2+)-mediated pathways of T cell activation by a mechanism that involves abrogation of the autophosphorylation of the multifunctional Ca2+/calmodulin kinase (CaM kinase II) and induction of protein phosphatase activity. Primary human T cells were stimulated with the combination of ionomycin and phorbol ester in the presence or absence of dexamethasone (Dex) (10(-6)-10(-12) M). Stimulation of T cells resulted in a rapid activation of CaM kinase II and protein kinase C (PKC) activity as determined by the phosphorylation of synthetic peptide substrates recognized by these enzymes. Dex inhibited the activity of CaM kinase II but not PKC activity in a dose-dependent fashion (minimum effective dose 10(-10) M). Stimulation of 32P-labeled T cells induced a rapid increase in the phosphorylation level of CaM kinase II which was inhibited by Dex. The inhibitory effect of Dex on this enzyme was fully reversed in the presence of the phosphatase inhibitor okadaic acid (250 nM) or RU 486, a glucocorticoid antagonist. These results suggest that GC inhibit the activation of CaM kinase during T cell activation through a mechanism that involves both the GC receptor and protein phosphatases 2A and/or 1. Inhibition of protein phosphorylation through the induction of protein phosphatase activity may represent a novel mechanism for the diverse effects of GC on eukaryotic cells.

Amino Acid Sequence↗
PubMed1995

Systemic lupus erythematosus: emerging concepts. Part 2: Dermatologic and joint disease, the antiphospholipid antibody syndrome, pregnancy and hormonal therapy, morbidity and mortality, and pathogenesis.

PURPOSE: To review 1) advances in the pathogenesis, diagnosis, and management of dermatologic and joint disease and the antiphospholipid antibody syndrome in patients with systemic lupus erythematosus; 2) controversies related to pregnancy and hormonal therapy and to morbidity and mortality in these patients; and 3) current views on the pathogenesis of systemic lupus erythematosus. DATA SOURCES AND STUDY SELECTION: Review of the English-language medical literature with emphasis on articles published within the last 5 years. More than 400 articles were reviewed. DATA SYNTHESIS: Despite considerable overlap, cutaneous lesions specific to lupus erythematosus may be divided into subsets with distinct clinical, histologic, and immunofluorescent features. A recent short-term, prospective, uncontrolled trial found hydroxychloroquine and retinoids to be of similar efficacy in the treatment of cutaneous lupus erythematosus. Optimal treatment for patients with lupus and the anticardiolipin antibody syndrome remains to be defined; uncontrolled, retrospective, and treatment-withdrawal studies suggest that warfarin may be more protective than aspirin. Whether pregnancy induces lupus flares has not yet been established; existing data suggest both that it does and that it does not. Oral contraceptive use and postmenopausal estrogen replacement therapy appear not to cause clinical deterioration in patients with lupus. Recent studies have documented a substantial improvement in the survival of patients with systemic lupus erythematosus; they found 5-year survival rates of 90% or more and 10-year survival rates of more than 80%. Most data suggest that systemic lupus erythematosus results from the activation of self-reactive T cells and B cells by genetic or environmental factors. CONCLUSIONS: The optimal treatment for dermatologic disease and the antiphospholipid antibody syndrome in patients with systemic lupus erythematosus remains unknown. Although mortality has decreased substantially, the morbidity related to the disease itself and to complications of therapy is still considerable. More studies are needed to further elucidate the effects of pregnancy on this condition and the pathogenetic mechanisms responsible for the development of this disease.

Antiphospholipid Syndrome↗
PubMed1995

Systemic lupus erythematosus: emerging concepts. Part 1: Renal, neuropsychiatric, cardiovascular, pulmonary, and hematologic disease.

PURPOSE: To review advances and controversies in the diagnosis and management of systemic lupus erythematosus with visceral involvement (renal, neuropsychiatric, cardiopulmonary, and hematologic disease). DATA SOURCES AND STUDY SELECTION: Review of the English-language medical literature with emphasis on articles published in the last 5 years. More than 400 articles were reviewed. DATA SYNTHESIS: Recent debates pertaining to lupus nephritis have focused on the value of kidney biopsy data and the role of cytotoxic drug therapies. Many studies have shown that estimates of prognosis are enhanced by consideration of clinical, demographic, and histologic features. For patients with severe lupus nephritis, an extended course of pulse cyclophosphamide therapy is more effective than a 6-month course of pulse methylprednisolone therapy in preserving renal function. Adding a quarterly maintenance regimen to monthly pulse cyclophosphamide therapy reduces the rate of exacerbations. Plasmapheresis appears not to enhance the effectiveness of prednisone and daily oral cyclophosphamide. Small case series have shown pulses of cyclophosphamide to be beneficial in patients with lupus and neuropsychiatric disease refractory to glucocorticoid therapy, acute pulmonary disease (pneumonitis or hemorrhage), and thrombocytopenia. Patients with systemic lupus erythematosus have an increased prevalence of valvular and atherosclerotic heart disease, apparently because of factors related to the disease itself and to drug therapy. CONCLUSIONS: Cytotoxic agents are superior to glucocorticoid therapy for the treatment of proliferative lupus nephritis, but the optimal duration and intensity of cytotoxic therapy remain undefined. Definitive studies of the treatment of autoimmune thrombocytopenia and acute pulmonary disease and of the diagnosis and treatment of neuropsychiatric disease are not available.

Cardiovascular Diseases↗
PubMed1995

High-risk features of lupus nephritis: importance of race and clinical and histological factors in 166 patients.

BACKGROUND: The pleomorphic nature of lupus nephritis has confounded efforts to refine estimates of prognosis. Consideration of interactions among prognostic factors may help to identify high-risk patients. METHODS: By univariate and multivariate survival analysis, race and attributes of severe active lupus nephritis were evaluated as potentially important prognostic factors in 166 patients upon entry into prospective therapeutic trials of lupus kidney disease. RESULTS: Black patients were significantly more likely than others to develop renal insufficiency. Cellular crescents emerged as the most predictive active pathological feature and interstitial fibrosis was the strongest chronic histological prognostic factor. Combinations of these morphological attributes identified particularly high-risk individuals. Patients with 50% or more cellular crescents and those with less extensive cellular crescents plus moderate to severe interstitial fibrosis were at markedly increased risk for doubling serum creatinine compared to those who lacked these histologic features (P < 0.0001). Azotaemia, anaemia, hypocomplementaemia, hypertension, tubular atrophy and glomerular sclerosis were also associated with an increased probability of renal function deterioration. Serum creatinine, haematocrit, race, and kidney pathology data emerged as independent predictors of renal insufficiency. Black patients in this study were more likely than the others to have high-risk histological features, including extensive cellular crescents (> or = 50%) and moderate to severe interstitial fibrosis, prior to randomization. CONCLUSIONS: Combinations of high-risk demographic, clinical and histological attributes identify patients at increased risk for progressive renal function deterioration. Several factors, including the severity of kidney biopsy findings, probably contribute to the poor prognosis of Black patients in this study population.

Adult↗
PubMed1994

Structure of the VH and VL segments of monoreactive and polyreactive IgA autoantibodies to DNA in patients with systemic lupus erythematosus.

Anti-DNA IgA autoantibodies play an important immunopathologic role in SLE patients. To analyze the cellular origin and the VH and VL structure of anti-DNA IgA autoantibodies, we generated five IgA1 mAbs to DNA using B lymphocytes from three SLE patients. Two mAbs bound to ssDNA only and one to both ssDNA and dsDNA (monoreactive antibodies). The remaining two mAbs bound to DNA (one to ssDNA and the other to both ssDNA and dsDNA) and to other self and foreign Ag (polyreactive antibodies). The IgA mAb relative avidity for DNA ranged from 7.5 x 10(-8) to 8.0 x 10(-10) g/microliters. The anti-DNA IgA mAb used VH segments of the VHI(VI-3b), VHII (VH2-MC2), VHIII (WHG16G and VH26c), and VHIV (V71-2) families in conjunction with V kappa I, V kappa IIIb, or V lambda I segments. All IgA mAb VH segments were juxtaposed with JH4b segments. The heavy chain CDR3 sequences were divergent in composition and length. When compared with those of the closest reported germ line genes, the IgA mAb VH and VL gene sequences displayed a number of differences. That these differences represented somatic point mutations was formally proved in both the monoreactive IgA mAb 412.67.F1.3 and the polyreactive IgA mAb 412.66.F1 VH segments by differential PCR amplification and cloning and sequencing of genomic DNA from the mAb-producing cell lines and autologous polymorphonuclear cells. The sequences of the germ line genes that putatively gave rise to the mAb 412.67.F1.3 and mAb 412.66.F1 VH segments were identical with those of the WHG16G and VH26c genes, respectively. In not only the monoreactive mAb 412.67.F1.3 but also the polyreactive mAb 412.66.F1 and mAb 448.9G.F1 VH segments, the higher concentration of replacement (R) mutations and the higher R:S (silent) mutation ratios in the complementarity-determining region (infinity; 19:0) than in the framework region (1.0) (p = 0.00001, chi 2 test) were highly consistent with selection by Ag. In the five IgA mAb VH and VL segments, the putative and verified somatic point mutations yielded 68 amino acid replacements, of which 38 were nonconserved. Twenty of these yielded positively charged or polar residues that play a major role in DNA binding, including seven Arg, five Lys, three Tyr, two Gln, two His, and a Thr. The conserved amino acid changes included seven Asn. These findings suggest that anti-DNA IgA autoantibodies use a broad selection of VH and VL genes and enhance their fit for Ag by undergoing somatic hypermutation and Ag selection.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Predicting renal outcomes in severe lupus nephritis: contributions of clinical and histologic data.

Despite several years of intense investigation, there continues to be controversy about the value of clinical, demographic and histologic features in prediction of outcomes of lupus nephritis. In addition, contemporary treatments have reduced the risk of progressive renal injury and thus may have altered the prognostic significance of some of these factors. We have therefore re-examined the predictive value of variables previously associated with an increased risk of renal insufficiency by studying 65 patients with severe lupus nephritis treated with intensive regimens of intravenous pulse cyclophosphamide or methylprednisolone. Five clinical features at study entry were each associated with an increased probability of doubling the serum creatinine: age greater than 30 years, Black race, hematocrit less than 26%, serum creatinine greater than 2.4 mg/dl, and C3 complement less than 76 mg/dl. By multivariate survival analysis, serum creatinine, hematocrit and race emerged as the strongest set of independent clinical predictors; the other clinical and demographic factors, including age and C3 complement did not contribute significantly to outcome predictions in the context of these three variables. Renal biopsy evaluation offered additional prognostic information and showed that patients with severe active and chronic histologic changes were at increased risk for developing renal insufficiency. The combination of cellular crescents and interstitial fibrosis was particularly ominous. Outcome predictions based on the strongest clinical model (serum creatinine, hematocrit and race) were significantly enhanced by the addition of renal pathology data. Consideration of these prognostic factors may contribute to decisions regarding the type and intensity of immunosuppressive therapy for patients with lupus nephritis.

Adult↗
PubMed1994

Serologic markers of lupus nephritis in patients: use of a tissue-based ELISA and evidence for immunopathogenic heterogeneity.

In order to assess the ability of various serologic assays to correlate with lupus nephritis, we analysed sera obtained from 60 patients with systemic lupus erythematosus (SLE). Patients were categorized as having active nephritis (group 1), active lupus without nephritis (group 2), inactive lupus with prior nephritis (group 3), or inactive lupus without prior nephritis (group 4). Three parameters were assessed including anti-dsDNA antibodies (Farr assay), immune complexes (C1q binding), and anti-C1q antibodies (salt-stable C1q binding). Additionally, glomerular binding activity (GBA) was measured using a new solid-phase immunoassay that detects immune elements by their ability to bind glomerular tissue. We found that patients with nephritis (group 1) exhibited higher mean values for each assay than patients in each of the other three groups (P = 0.001, 0.009, 0.14, and 0.23 in the GBA, C1q, anti-dsDNA, and anti-C1q assays, respectively). The only assay which distinguished patients with nephritis (group 1) from patients having active disease without nephritis (group 2) was the GBA (mean 0.48 +/- 0.09 versus 0.15 +/- 0.04, P < 0.05). In terms of utility, all tests were specific for diagnosing nephritis among patients with lupus; however, only the GBA was reasonably sensitive. The information provided by the anti-dsDNA and C1q assays were not correlated with one another, nor additive to the GBA. Patients with false negative GBA tended to have received more intensive immunosuppression. The qualitative characteristics of GBA varied among patients with nephritis. These data suggest the pathogenesis of lupus nephritis is complex, and may be mediated by an array of immune elements. Moreover, the data indicate the potential utility for a broad tissue-based approach to detection of pathogenic immune elements over other, specific immunologic markers.

Antibodies, Antinuclear↗
PubMed1994

A pilot study of anti-CD5 ricin A chain immunoconjugate in systemic lupus erythematosus.

OBJECTIVE: To determine the safety and clinical and biological effects of a murine monoclonal anti-CD5 ricin A chain immunoconjugate (CD5 Plus) in patients with systemic lupus erythematosus (SLE). METHODS: An open label phase I study of CD5 Plus. A dose of 0.1 mg/kg was administered intravenously on 5 consecutive days. A second course of immunoconjugate was given to patients who failed to show any clinical response one to 2 months later. RESULTS: Six patients (4 with glomerulonephritis and 2 with thrombocytopenia) were studied. Improvement was documented in 2 patients with nephritis; no effect on thrombocytopenia was observed. Adverse effects were mild and transient. Relative to pretreatment lymphocyte counts, the mean reduction in CD3+ T cell count was 69% at 2 weeks, 32% at one month, and 34% at 6 months following initial treatment. A comparable decrease in all subpopulations of mature T cells was noted, using a variety of surface markers, including CD4 and CD8. The mean percentage of T cells expressing the activation markers HLA-DR and interleukin 2R (IL-2R) was high before treatment, and remained so. There was a transient decrease in CD5+ B cells, but no persistent depletion of total B cell numbers. There was no consistent change in natural killer cell populations. CONCLUSION: Anti-CD5 ricin A chain immunoconjugate is well tolerated in patients with SLE, causes modest T cell depletion which may persist for months, and may have some clinical efficacy in lupus nephritis.

Antibodies, Monoclonal↗