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Biomedical subjects

J A Rump

Publications and source records attributed to J A Rump.

At least 19 recordsLinked to original sources
PubMed1997

A double-blind, placebo-controlled, crossover therapy study with natural human IL-2 (nhuIL-2) in combination with regular intravenous gammaglobulin (IVIG) infusions in 10 patients with common variable immunodeficiency (CVID).

Ten CVID patients with defective IL-2 synthesis in vitro were treated with nhuIL-2 in a placebo-controlled, double blind, crossover therapy study during a period of 12 months. No severe side-effects of nhuIL-2 were recorded. Marginal serum nhuIL-2 levels were measurable in individual patients only during the therapy phase. Serum levels of soluble IL-2 receptors were unaffected by the therapy. nhuIL-2 and placebo groups did not differ significantly with respect to requirement of IVIG substitutions which were performed whenever serum IgG levels dropped below 5 g/l: a total of 53 IVIG infusions (corresponding to 17.6 g IgG/month per patient) was necessary during the placebo phase, and 48 infusions (16.4 g IgG/month per patient) during the nhuIL-2 treatment phase. Thus, nhuIL-2 therapy was ineffective in improving spontaneous IgG synthesis in vivo. Nevertheless, the group of patients receiving nhuIL-2 during the first 6 months of the study exhibited a significant reduction of severe infections (n = 25) during the following 6 months of placebo treatment (n = 7) (P<0.045). The infection score dropped in this group from 181 to 23 (P<0.015). Patients of the second group receiving first placebo and then nhuIL-2 did not experience a significant difference in number and score of infectious episodes: 25 infections were recorded during the first 6 months and 24 during the following 6 months. We suppose that nhuIL-2 therapy of CVID patients reduces susceptibility to severe infections, possibly via the induction of a specific antibody response, which is effective at the earliest 6 months after initiating nhuIL-2 therapy.

Adult↗
PubMed1997

Isolation of Helicobacter pullorum from patients with enteritis.

Helicobacter pullorum, recently described as sp. nov., is commonly isolated from asymptomatic poultry. Two cases of human enteritis associated with H. pullorum, one of them in an immunocompromised patient, are reported. Problems in the correct species identification by means of phenotypic and genotypic methods are discussed and for the first time a fatty acid pattern of Helicobacter pullorum is presented.

Adult↗
PubMed1996

Clinical utility of cytomegalovirus urine cultures for ophthalmic care in patients with HIV.

BACKGROUND: The utility of cytomegalovirus (CMV) urine cultures was checked in patients with HIV (a) to identify those at risk for CMV retinitis and (b) to guide clinical decisions on treatment and prophylaxis of CMV retinitis. METHODS: HIV infected patients were tested for CMVuria by shell vial cell cultures. The prevalence of CMVuria was related to CD4 count, HIV risk group, and time before and after diagnosis of CMV retinitis. RESULTS: A total of 639 shell vial cell cultures were obtained from 266 HIV infected ophthalmic patients. Only 4% of all patients with a CD4 count > 400 x 10(6)/l shed CMV in their urine compared with 42% with a CD4 count < or = 50 x 10(6)/l. Twenty three of 25 patients with CMV retinitis had a CD4 count < or = 50 x 10(6)/l. Among 130 patients with a CD4 count < or = 50 x 10(6)/l (a) those who were CMVuric had a nearly sevenfold risk (p < 0.0001) of developing CMV retinitis (35%) compared with those who did not shed CMV in their urine (5%), and (b) CMVuria and CMV retinitis were more frequent in homosexuals (58%/25%) than in intravenous drug users (23%/15%). More than 1 year before diagnosis of CMV retinitis 18% of patients were CMVuric compared with 83% of patients who were CMV culture positive in the last 3 months. CMVuria under virustatic maintenance therapy is associated with worsening of retinitis in two thirds of cases. CONCLUSION: Ophthalmic screening of patients with HIV should include those with a CD4 count < or = 50 x 10(6)/l and focus on the subgroup with additional CMVuria. Screening of other patients can be dropped without undue risk in order to spare AIDS patients unnecessary hospital visits. CMVuria as a single finding, however, does not justify antiviral prophylaxis of CMV retinitis.

AIDS-Related Opportunistic Infections↗
PubMed1995

Leukocytoclastic vasculitis and long-term remission in a patient with secondary AML and post-remission treatment with low-dose interleukin-2.

Interleukin-2 (IL-2) has been licensed for the treatment of renal cell carcinoma and is currently being evaluated as a therapeutic agent in hematological malignancies. It is associated with a variety of side effects due to induction of a nonspecific inflammatory response. However, phenomena of autoimmunity have also been reported. Here we describe a patient with secondary acute myeloid leukemia who developed a leukocytoclastic vasculitis during long-term post-remission treatment with very low doses of IL-2.

Adrenal Cortex Hormones↗
PubMed1995

Common variable immunodeficiency (CVID) and MxA-protein expression in blood leucocytes.

The underlying immunopathogenic mechanism of CVID has been suspected to involve a chronic viral infection or an autoimmune condition. However, formal proof of viral infection is lacking. Measurement of MxA-protein in leucocyte lysates is a sensitive test for evaluating the activation of the host's interferon system. Both viral infections and autoimmune diseases such as systemic lupus erythematosus (SLE) strongly induce MxA-protein in peripheral leucocytes. We therefore examined 15 patients with longlasting hypogammaglobulinaemia for MxA-protein induction in vivo: 13 patients suffered from CVID, one from hyper-IgM syndrome, and one patient had chronic B lymphocytic leukaemia associated with immunoglobulin deficiency and chronic papilloma virus infection (condylomata accuminata). Only the latter patient exhibited a strong MxA-protein expression; two CVID patients were borderline positive, and the remaining 12 patients including the hyper-IgM syndrome were MxA-protein-negative. There was no relationship between MxA expression and low CD4/CD8 ratios or increased CD8/CD57+ T cell counts, although both conditions are often observed in CVID as well as in chronic viral infections. When exposed in vitro to interferon-alpha (IFN-alpha), peripheral blood leucocytes of four MxA-negative patients were capable of producing normal amounts of MxA-protein. Taken together, these results argue against a viral or autoimmune pathogenesis of CVID.

Adult↗
PubMed1995

Two novel cationic staphylococcal proteins induce IL-2 secretion, proliferation and immunoglobulin synthesis in peripheral blood mononuclear cells (PBMC) of both healthy controls and patients with common variable immunodeficiency (CVID).

Two cationic proteins, a neutral phosphatase (NP-tase) and a 70-kD protein (p70) were isolated from Staphylococcus aureus by ion exchange chromatography. We compared their properties to those of the well established B cell mitogen of whole, fixed Staph. aureus strain Cowan I cells (SAC). Both purified proteins were able to induce immunoglobulin synthesis in PBMC cultures of healthy donors. NP-tase and p70 also induced immunoglobulin synthesis of PBMC from those patients with CVID who were also responsive to SAC plus IL-2 stimulation. Immunoglobulin synthesis in response to NP-tase and to p70 was time- and dose-dependent and could be inhibited by addition of specific antibodies against the proteins. In contrast to SAC, no addition of exogenous IL-2 was necessary to obtain maximal immunoglobulin synthesis induced by NP-tase or p70. However, neither protein was able to induce immunoglobulin synthesis in B cell-enriched cultures. High amounts of IL-2 were found in supernatants of PBMC from healthy donors following stimulation with low concentrations of NP-tase or p70, and this was associated with vigorous lymphocyte proliferation. Both proteins behave like typical antigens, and not like lectins or superantigens, since an NP-tase-stimulated T cell line showed an antigen-specific, MHC-restricted secondary response. In addition, no preferential T cell receptor V beta chain usage was found with eight V beta-specific MoAb. It is likely that the two proteins induce antigen-specific T cell activation, which is then followed by polyclonal activation of B cells via CD40 receptors and cytokine release.

Adult↗
PubMed1995

[Defects in the immunoglobulin producing cells in bone marrow of patients with variable immunodeficiency syndrome].

The number of plasma cells, IgG+, IgA1+, IgA2+ and IgM+ cells were determined in bone marrow (BM) biopsies of 12 patients with common variable immunodeficiency syndrome (CVID) and 12 controls without signs of immunodeficiency. Controls had a median of 11 plasma cells/mm2, 76 IgG+, 76 IgA+ and 18 IgM+ cells/mm2 BM, respectively. Compared with the control group, the CVD patients showed a significant reduction of each cell type (p < 0.001). They also demonstrated a close correlation between low numbers of IgG+ and IgA+ cells in the BM and low IgG and IgA serum levels. In general, there was also a good correlation of the IgM+ cells and the respective IgM levels in the serum, except 2 CVID patients with normal IgM serum levels and subnormal numbers of IgM+ cells in the BM. Our results showed that there was an almost complete coincidence between the reduced numbers of Ig-producing cells in the BM and low serum levels of the respective Ig isotype. Thus, immunohistological analysis may be of additional help for the diagnosis of immunodeficiency.

Antibody-Producing Cells↗
PubMed1994

Intestinal B cell defects in common variable immunodeficiency.

The humoral immune system of the small intestine of 17 patients with common variable immunodeficiency (CVID) was studied by immunohistology using antibodies specific for IgA1,2, IgM, IgG1-4, the J chain and the secretory component (SC). IgA1,2+, IgG2+ and IgM+ lamina propria B cells were totally lacking in 65% (11/17), 41% (7/17) and 18% (3/17) of CVID patients, respectively. One patient exhibited an isolated IgA1 subclass deficiency. The proportion of plasma cells in conventionally stained histological sections of the same intestinal biopsies showed a close correlation with the numbers of IgA+ and IgM+ cells. Considerable numbers of J chain-synthesizing cells were present in all patients with CVID, indicating the presence of early B cells unable to differentiate into immunoglobulin-producing plasma cells. Most of the patients with intestinal IgA and/or IgM defects strongly expressed the SC in their enterocytes, suggesting an immunoglobulin-independent regulation of the SC. Clinically, only CVID patients with intestinal IgA defects developed intestinal infections with Giardia lamblia, Campylobacter jejuni or Candida albicans. The outcome of in vitro immunoglobulin synthesis assays with peripheral blood lymphocytes did not predict the presence or absence of the respective isotype-producing B cells in the intestinal lamina propria. Thus, immunohistological examinations of intestinal biopsies are required to determine the extent of mucosal immunodeficiency in CVID patients.

Adolescent↗
PubMed1994

[Differential diagnostic aspects of lethal midline granulomas (granuloma gangraenescens].

The lethal midline granuloma and limited Wegener's granulomatosis show clinical similarity, although they are of different etiology. The following case of a 53-year-old woman shows how difficult it is to establish the precise diagnosis of lethal midline granuloma. The diagnosis depends on the pathological finding of a lymphoma. The lymphoma can be differentiated in a T- or a B-cell lymphoma by immunostaining. However, the diagnostic yield of biopsies from the nose is not perfect. It would be, therefore, important to find other diagnostic criteria. The presence of the c-ANCA is a helpful tool, but in the case of limited Wegener's granulomatosis, it has a sensitivity of 50%. The prognosis of the lethal midline granuloma is poor even if an adequate radiation therapy is instituted.

Diagnosis, Differential↗
PubMed1993

p-ANCA of undefined specificity in ulcerative colitis: correlation to disease activity and therapy.

Sera of 108 patients with chronic inflammatory bowel disease (IBD) and 13 sera from patients with other gastrointestinal diseases were screened for antibodies against neutrophil cytoplasmic antigens (ANCA) by an indirect immunofluorescence test. 37 out of 64 sera (58%) from patients with ulcerative colitis (UC) produced a fine granular and perinuclear ANCA staining pattern ("snowdrift-like" p-ANCA) clearly different from the cytoplasmic ANCA fluorescence (c-ANCA) seen in active Wegener's granulomatosis (WG) and the typical p-ANCA pattern produced by anti-myeloperoxidase (MPO) autoantibodies. Only 1 of 44 sera from patients with Crohn's disease (CD) and none of the control sera showed positive "snowdrift-like" p- ANCA reactions. 31 out of the 37 p-ANCA positive sera (84%) were obtained from patients with high disease activity with and without longterm high dose steroids. p-ANCA titers became negative after longterm steroid therapy and following complete colectomy.

Adult↗
PubMed1993

[Preliminary results in a placebo-controlled, double-blind crossover clinical trial with human interleukin-2 (n-IL-2) in patients with variable immunodeficiency syndrome (CVID)].

Ten CVID patients with an in vitro defect for IL-2-synthesis were treated for 12 months in a placebo-controlled double-blind crossover therapy study with human natural IL-2 s.c. There were no severe side effects of n-IL-2 recorded. Serum levels of soluble IL-2 receptors were unaffected by the therapy. Serum IL-2 levels were only measurable in single patients during the therapy phase. Since verum and placebo groups did not differ with respect to requirement for intravenous gammaglobulin substitutions, n-IL-2 therapy was uneffective in switching on IgG synthesis in vivo. Nevertheless, there was an elevation in vitro of IgM synthesis in 5 patients and of IgG synthesis in 4 patients during n-IL-2 therapy after stimulation of patients' lymphocytes with staphylococcus aureus Cowan I (SAC) plus n-IL-2 or with Pokeweed Mitogen (PWM) without n-IL-2. Additionally, an elevated IL-2-synthesis in vitro was recorded after OKT3 stimulation for 3 CVID patients. There was a significant reduction of severe infections from 25 during the first 6 months of the study to 7 infections during the following 6 months, in the group of patients which received n-IL-2 first. In the second group, which received placebo first, there were no significant differences between placebo and n-IL-2 therapy phase detectable (25 infections during the first 6 months of the study and 24 severe infections in the second phase).(ABSTRACT TRUNCATED AT 250 WORDS)

Common Variable Immunodeficiency↗
PubMed1992

Treatment of diarrhoea in human immunodeficiency virus-infected patients with immunoglobulins from bovine colostrum.

Diarrhoea and weight loss are found in more than 50% of patients with the acquired immunodeficiency syndrome (AIDS). In some patients the symptoms can be very severe, leading to death even in the absence of opportunistic infections. In 30% of these patients, enteric pathogens cannot be identified, and approximately only half of the identifiable aetiologic agents of diarrhoea in patients infected with the human immunodeficiency virus (HIV) were treatable with antibiotics. Immunoglobulins from bovine colostrum (Lactobin, Biotest, Dreieich, FRG) contain high titers of antibodies against a wide range of bacterial, viral and protozoal pathogens as well as against various bacterial toxins. Lactobin (LIG) is quite resistant to 24-h incubation with gastric juice. In a multi-center pilot study 37 immunodeficiency patients with chronic diarrhoea [29 HIV-infected patients, 2 patients with common variable immunodeficiency (CVID), one unidentified immunodeficiency, five patients with graft versus host disease (GvHD) following bone marrow transplantation] were treated with oral LIG (10 g/day for 10 days). Good therapeutic effects were observed. Out of 31 treatment periods in 29 HIV-infected patients 21 gave good results leading to transient (10 days) or long-lasting (more than 4 weeks) normalisation of the stool frequency. The mean daily stool frequency decreased from 7.4 to 2.2 at the end of the treatment. Eight HIV-infected patients showed no response. The diarrhoea recurred in 12 patients within 4 weeks (32.4%), while 19 patients were free of diarrhoea for at least 4 weeks (51.3%). In 5 patients intestinal cryptosporidiosis disappeared following oral LIG treatment. LIG treatment was also beneficial in 4 out of 5 GvHD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Possible role of IL-2 deficiency for hypogammaglobulinaemia in patients with common variable immunodeficiency.

Common variable immunodeficiency (CVID) patients are unable to produce specific immunoglobulins after antigen contact in vivo. The aim of this study was to investigate whether in some cases of CVID a decreased de novo synthesis of IL-2 might be the cause of immunodeficiency and whether this deficiency can be corrected by IL-2 supplementation in vitro. Mononuclear cells from 17 CVID patients and from 10 healthy controls were cultured with monoclonal anti-CD3 antibody OKT3, pokeweed mitogen (PWM) or tetanus toxoid (TT) to stimulate IL-2 synthesis. In parallel, in vitro IgG and IgM synthesis was stimulated with Staphylococcus aureus Cowan I (SAC), PWM or TT in the presence or absence of IL-2. While lymphocytes of 11 out of 17 patients produced low to normal amounts of IL-2 upon stimulation with anti-CD3, only three patients showed low IL-2 production in response to PWM and five in response to TT. Regarding immunoglobulin synthesis in vitro, five patients completely failed to produce IgM or IgG upon stimulation with PWM, SAC or TT irrespective of the addition of IL-2. By contrast, four patients did not show any defect in vitro and synthesized normal amounts of IgM and IgG with any of the three stimuli. Finally, eight patients could be reconstituted for PWM-, SAC- and TT-induced IgM and/or IgG synthesis in vitro, by adding IL-2 to the culture system. This enhancing effect of IL-2 could be blocked by adding anti-IL-2 receptor antibodies to the cultures. Our findings indicate that a defective IL-2 synthesis after antigen stimulation may be one reason for the impaired immunoglobulin production in some cases of CVID.

Adult↗