More on MHC class II deficiency.
Explore the source record for details and available documents.
Anemia, Hemolytic, Autoimmune↗
Biomedical subjects
V Wahn
Publications and source records attributed to V Wahn.
Early surgery of the intestinal tract in infants--a possible risk factor for subsequent latex allergy?
Explore the source record for details and available documents.
Anaphylaxis↗
Deficiency of late complement components in patients with severe and recurrent meningococcal infections.
Explore the source record for details and available documents.
Adult↗
Mite allergy, clinical atopy, and restriction by HLA class II immune response genes.
From a community-based study cohort of 1812 elementary schoolchildren we selected 129 unrelated participants to investigate the relevance of HLA-class II molecules (DPB, DQB, and DRB) to the regulation of immune response to the mite allergen Der p 1 and to clinical atopic disorders. On the basis of skin prick test results validated by measurement of specific IgE, individuals were selected and divided into three groups: group I (n = 20), controls without detectable specific IgE to common inhalant allergens; group II (n = 22), children sensitized only to non-mite allergens; group III (n = 85), children sensitized to Der p 1. Clinical history of asthma, eczema, and hay fever was ascertained using standardized questionnaires. In total, 43 different HLA class II alleles (DPB, n = 19; DQB, n = 14; and DRB, n = 10) were determined by sequence-specific oligonucleotide typing with PCR-amplified DNA. We were not able to demonstrate significant differences in gene frequencies of any HLA class II allele between the group of mite-sensitized children and one of the other two groups. However, the presence of certain DRB- and DPB-haplotypes (DRB *0100/*0300/*1100 and DPB *0201/*0401) was significantly associated (p < or = 0.01) with a history of asthma, hay fever, and atopy (defined as a history of asthma and/or hay fever and/or eczema). Other haplotypes, including DQB *0303/*0503, DRB *0200/ *0700, and DPB 0402 were negatively associated with a history of eczema, hay fever, and atopy (p < or = 0.01). Thus, our findings do not suggest a relevance of HLA-class II molecules to mite allergy; however, some HLA class II haplotypes appear to be predictive of the incidence of atopic disorders.
Allergens↗
Severe combined immunodeficiency (SCID) associated neutropenia: a lesson from monozygotic twins.
A case of severe combined immunodeficiency (SCID) in monozygotic twin sisters was detected at 3 months of age with neutropenia in one twin and a normal differential count in the other. The neutropenic twin, suffering from severe skin ulcers, was successfully treated with granulocyte colony stimulating factor (G-CSF). Discordant occurrence of neutropenia in identical twins shows that there may be a non-genetic cause for the neutropenia in SCID. Suppression of myelopoiesis was probably induced by activated maternal T cells. The neutropenia in this case may thus be classified as SCID associated neutropenia, as opposed to reticular dysgenesis, in which the neutropenia is G-CSF refractory and is most probably caused by a genetic stem cell defect. A response to G-CSF in a neutropenic child with SCID can be clinically beneficial and might help to distinguish between G-CSF unresponsive reticular dysgenesis and G-CSF responsive SCID associated neutropenia.
Diseases in Twins↗
Nitric oxide induces apoptosis in mouse thymocytes.
Nitric oxide (NO) produced at high concentrations by the inducible NO synthase is an important effector molecule involved in immune regulation and defense. We have examined whether NO represents a signal for triggering apoptosis in thymocytes. Freshly isolated thymocytes were incubated with different chemical NO donors for various intervals. Apoptosis was determined by detection of DNA strand breaks with in situ nick translation. All NO donors induced thymocyte apoptosis with 30% positive thymocytes vs 10% in controls after 8 h. Apoptosis was prevented by addition of ZnSO4. Short-term pre-exposure to NO resulted in protection from apoptosis induced by glucocorticoids comparable with the protective effect of heat shock. Flow cytometry revealed that NO treatment as well as heat shock or dexamethasone incubation is accompanied by reduction in the CD4+ CD8+ thymocyte subpopulation. Apoptosis induction was accompanied by increased expression of p53, as detected by PCR analysis 2 h after NO donor addition. In vivo treatment of mice with endotoxin results in increased thymic apoptosis. Focal apoptosis was found to occur in close proximity to blood vessels 18 h after LPS treatment. Capillary endothelium and dendritic cells adjacent to apoptotic foci were found to stain strongly for inducible NO synthase expression. Furthermore, in an in vitro experiment using cocultures of thymocytes with LPS/cytokine-activated endothelial cells expressing inducible NO synthase, a significantly increased rate of thymocyte apoptosis was found, and this could be prevented completely by inhibiting NO production. Addition of dexamethasone to these cocultures did not lead to a further increase in the percentage of apoptotic thymocytes, underlining the protective effect of NO on dexamethasone-induced apoptosis.
Animals↗
Cytokines in neutrophil-dominated airway inflammation in patients with cystic fibrosis.
Bronchopulmonary disease in patients with cystic fibrosis (CF) is a paradigm of neutrophil-dominated airway inflammation. We hypothesized that proinflammatory cytokines contribute to a localized neutrophil-dominated inflammatory state as present in CF airways. In a cross-sectional study, we analyzed 63 sputum samples from 33 CF patients for concentrations of the cytokines interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-8, tumor necrosis factor-alpha (TNF-alpha), and granulocyte-colony stimulating factor (G-CSF) by means of enzyme-linked immunosorbent assay. Furthermore, the activity of neutrophil elastase (NE) in the sputum samples was determined using a specific chromogenic substrate. Compared to sputum samples from 10 healthy controls, there were significantly increased concentrations of IL-1 beta, IL-8 and TNF-alpha in the CF sputum samples. The concentration of IL-8 correlated significantly with NE activity in the CF sputum samples. In CF patients with airways chronically colonized with Pseudomonas aeruginosa, IL-8 concentrations in sputum were significantly enhanced. In glucocorticoid-treated patients, IL-1 alpha and G-CSF sputum concentrations were significantly lower when compared to levels in the other patients. These results show that there are high concentrations of proinflammatory cytokines in CF airways which may contribute to the localized neutrophil-dominated inflammatory state found clinically.
Adolescent↗
Treatment of refractory juvenile chronic arthritis by monoclonal CD4 antibodies: a pilot study in two children.
OBJECTIVE--To study the effect of anti-CD4 treatment in patients suffering from refractory systemic onset juvenile chronic arthritis (JCA). METHODS--Two children were treated with the mouse CD4 antibody MAX.16H5. The effects on numbers of circulating CD4 T cells, clinical symptoms and C reactive protein (CRP) level were studied and the appearance of human antimouse immunoglobulin antibodies investigated. RESULTS--In patient one, disappearance of fever and malaise and a reduction of arthritic activity were observed together with a reduction in CRP. When disease activity returned eight weeks later, a second successful course of treatment was administered. It was possible to reduce the corticosteroid dosage permanently. In the other child, a first treatment cycle did not alter disease activity. A marked reduction in clinical and laboratory disease activity markers was observed after the second course. Only transient and mild side effects were observed. One patient exhibited a short lasting febrile reaction with chills, the other an urticarial rash. In both patients, human antibodies to mouse immunoglobulin became detectable. The decrease in the number of CD4 T cells in the peripheral blood was only short lasting and numbers returned to normal values within one to eight weeks, even after the second course of antibody treatment and under concomitant immunosuppressive treatment. No sustained clinical remissions could be achieved. CONCLUSIONS--These preliminary observations support the evidence of positive effects of CD4 antibody treatment in refractory systemic onset JCA. Long term efficacy, however, remains to be established.
Adolescent↗
Alpha 1-proteinase inhibitor abrogates proteolytic and secretagogue activity of cystic fibrosis sputum.
Airway disease in cystic fibrosis (CF) is characterized by neutrophil-dominated chronic inflammation with an excess of uninhibited neutrophil elastase (NE), which is regarded as an important factor in progressive lung destruction. Therefore, inhalation of alpha 1-proteinase inhibitor (alpha 1-PI) seems to be a reasonable therapeutic approach. To estimate its therapeutic potential, we quantitatively investigated the in vitro interactions of exogenous alpha 1-PI with CF sputum samples (n = 28). High NE and alpha 1-PI concentrations were detected in CF sputum (6.03 +/- 0.78 and 2.56 +/- 0.16 mumol/l, respectively). There was significant NE activity (2.6 +/- 0.4 U/l) due to both the surplus of NE and proteolytic degradation of alpha 1-PI. Addition of exogenous alpha 1-PI resulted in a dose-dependent inhibition of NE activity in CF sputum; > 90% inhibition was achieved at 10 micrograms/ml alpha 1-PI. Purified NE as well as CF sputum potently induced secretion from porcine tracheal glands. Corresponding to inhibition of NE activity, CF sputum-induced secretion was also inhibited by exogenous alpha 1-PI; > 90% inhibition was also achieved at 10 micrograms/ml alpha 1-PI. Incubation of exogenous alpha 1-PI with CF sputum for 24 h did not reduce the inhibitory effects. From our in vitro results we conclude that inhalation of alpha 1-PI might effectively inhibit both NE activity and airway gland hypersecretion in CF airways.
Adolescent↗
Papillon-Lefèvre syndrome--successful treatment with a combination of retinoid and concurrent systematic periodontal therapy: case reports.
Papillon-Lefevre syndrome is a rare autosomal-recessive congenital differentiation disorder; the external signs are hyperkeratosis of the palms and soles. Intraorally, the most salient manifestations are dystrophic periodontal problems that affect both the primary and permanent dentitions and frequently lead to premature tooth loss. Two children were treated with acitretin 0.5 mg/kg of body weight per day from November 1992 to November 1993, and another child since October 1993. Concurrently, the children received professional oral hygiene care (scaling, root planing, and curettage). The combination of retinoid therapy and periodontal treatment improved the dermatologic and periodontal conditions.
Acitretin↗
The use of intravenous immunoglobulins in symptomatic HIV infection. Results of a randomized study.
To study the efficacy of intravenous immunoglobulin in symptomatic infection with human immunodeficiency virus (HIV) we enrolled 35 patients with CD4 lymphocyte counts below 300/microliter in a randomized three-arm study. In addition to standard HIV treatment (e.g., zidovudine, aerosolized pentamidine), 13 patients were treated with 7.5 g and 11 with 40 g of a 7 S intravenous IgG preparation every 4 weeks over a period of 1 year. A control group of 11 patients remained on standard treatment. Clinical and laboratory parameters, including lymphocyte proliferation and in vitro immunoglobulin synthesis were evaluated prior to intravenous IgG administration. HIV-specific immunological abnormalities such as increased B-cell activation and B-cell immaturity were observed in all three study groups at the beginning of the study. Mitogen-induced lymphocyte proliferation was diminished. These disturbances were not influenced by intravenous IgG treatment. Further laboratory data and the course of the HIV infection (fever, antibiotic treatment, hospitalization, Candida and herpes simplex or cytomegalovirus infection) remained unchanged. Thus, our data with an observation period of 12 months do not support the use of intravenous IgG treatment in adult symptomatic HIV-infected patients with CD4 counts lower than 300/microliter.
AIDS-Related Opportunistic Infections↗
Interferon-gamma for treatment of severe atopic eczema in two children.
Two 4- and 5-year-old children suffering from refractory atopic dermatitis were treated with recombinant interferon-gamma (rIFN-gamma). rIFN-gamma was injected at 50 micrograms subcutaneously three times a week in the first child for 3 weeks, followed by three times 25 micrograms in week 4. In the other child two treatment courses of 4 weeks were given after a break of 2 weeks. Therapy was well tolerated. In child one reductions in eczematous body surface and severity of lesions were observed, while no beneficial effect was seen in the other. Clinical chemistry data remained unchanged. Immunological studies performed in parallel showed a decrease in total serum IgE of 50% in child 1, a decrease in spontaneous in vitro IgE production, an increase in in vitro production of interleukin-6, and a normalization of previously decreased in vitro lymphocyte responses to several mitogens. While marked immunological changes were noted during IFN-gamma treatment, clinical benefits were not encouraging. Diminished IFN-gamma production has been claimed to be a major pathogenic factor in atopic eczema. Our results indicate that the pathogenesis is more complex. Clinically, we were unable to confirm previous observations in adults. Further studies are needed before IFN-gamma can be recommended for therapy of pediatric atopic eczema.
Child, Preschool↗
Autoimmune haemolytic anaemia in a child with MHC class II deficiency.
A 3 year old Turkish girl is described who was suffering from major histocompatibility complex (MHC) class II deficiency syndrome, which is characterised by the lack of expression of HLA class II antigens on mononuclear cells. The presence of HLA class II genes was demonstrable at the DNA level. Combined immunodeficiency was indicated by hypogammaglobulinaemia and the absence of delayed type hypersensitivity on skin testing. Further, she was unable to produce specific antibodies towards foreign antigens and suffered from recurrent pulmonary, gastrointestinal, and septic infections from the third month of life. The clinical course was complicated by a Coombs test positive haemolytic anaemia due to the production of autoantibodies against the rhesus "e' antigen, a non-glycosylated protein antigen. Haemolysis could be controlled by oral steroid treatment. This case is of interest as it shows that despite the absence of HLA class II antigens and combined immunodeficiency autoimmune reactions with production of specific autoantibodies directed to protein antigens are possible.
Anemia, Hemolytic, Autoimmune↗
T-cell receptor V beta chain expression in patients with juvenile rheumatoid arthritis.
The V beta chain repertoire in peripheral blood T-cell was analyzed in 23 patients with juvenile rheumatoid arthritis (JRA). Of these, 15 patients had active disease as defined by tender and swollen joints. The ESR was elevated in all but three patients, C-reactive protein (CRP) was elevated in eight. Three patients were investigated during active and inactive phases of the disease. In the active phase of the disease T-cell composition was characterized by an increased number of CD4+ helper cells due to a marked increase in the CD4+CD45RA+ subgroup (34.0 +/- 10.9%, P < 0.001) and a decrease in CD8+CD29+ T-cells (10.3 +/- 5.6%, P < 0.05) compared to controls (15.4 +/- 10.0% and 17.8 +/- 12.3%, respectively). Using the monoclonal antibodies available to determine T-cell receptor (TCR) expression, patients with active disease demonstrated a significant predominance of T-cells bearing TCRs of the V beta 5 family as determined by flow cytometry (7.6 +/- 6.7 vs 3.4 +/- 1.3 in controls, P = 0.01). In active polyarthritis, up to 24% of peripheral blood T-cells expressed TCRs of the same family. In the majority of JRA patients and especially in non-active disease, no preferential TCRs were found compared to controls. However, even defining only a part of TCRs by immunofluorescence, in certain patients a preferential or dominant expression of a single V beta gene family in the T-cells was found, supporting the concept of an involvement of T-cells in the autoimmune pathogenesis of JRA.
Adolescent↗
Glycogen storage disease type Ib: infectious complications and measures for prevention.
A patient with glycogen storage disease (GSD) type Ib, neutrophenia, chronic inflammatory bowel disease and recurrent abscesses was treated with recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF). GM-CSF (and also granulocyte colony stimulating factor) therapy markedly increased the neutrophil counts and reduced the frequency of infections and inflammation. We conclude that myeloid growth factors are effective for the treatment and prevention of acute infections and chronic inflammatory complications in patients with GSD Ib.
Abscess↗
Interferon-gamma production by cord-blood mononuclear cells is reduced in newborns with a family history of atopic disease and is independent from cord blood IgE-levels.
For newborn children both elevated serum IgE levels in the cord blood and a positive family history of atopic disease have been shown to be risk factors for the manifestation of atopic diseases. In adult patients with atopic dermatitis, in vitro interferon-gamma (IFN-gamma) production is reduced and a negative correlation with serum IgE levels has been shown. We have now raised the question if newborn infants at risk for the development of atopic disease have similar abnormalities of cytokine production at birth. In vitro production of interleukin 2, interleukin 6 and interferon-gamma by peripheral blood mononuclear cells was measured in 53 newborns: 21 had cord blood IgE levels above 0.9 kU/l, 21 had a positive family history, 7 had both elevated IgE and a positive family history; 18 newborns with no identifiable risk for atopic disease served as controls. Umbilical cord blood mononuclear cells were stimulated with PHA or monoclonal antibody OKT3. In vitro production of interleukin 2 and 6 was comparable in all groups. Compared to controls IFN-gamma production of peripheral mononuclear cells (PBMC) from newborns with elevated cord blood IgE was not different, but PMBC from newborns with a familial risk showed a significant decrease in PHA induced IFN-gamma production (p < 0.005, U-test). No correlation between umbilical cord blood IgE and diminished IFN-gamma production was found in newborns with or without a positive family history. We conclude that immunoregulatory abnormalities in newborns of atopic families are detectable already at birth and are unrelated to cord blood IgE.
Adult↗
Inhibition of adhesion of S-fimbriated E. coli to buccal epithelial cells by human skim milk is predominantly mediated by mucins and depends on the period of lactation.
Expression of S-fimbriae is frequent in Escherichia coli strains causing sepsis and meningitis in the newborn period. We analysed the ability of human skim milk to inhibit adhesion of S-fimbriated E. coli to human buccal epithelia. Adhesion was inhibited by up to 90% using colostrum (5%) and up to 50% with mature milk (5%), indicating that this anti-infective mechanism depends on the period of lactation. Elimination of up to 99% of immunoglobulins and 91% of lactoferrin by affinity chromatography had no effect on the inhibition of adhesion. After separation of high- (> 10 kD) and low-molecular-weight fractions of skim milk, only the fraction > 10 kD was found to be able to inhibit bacterial adhesion. In order to further characterize receptor molecules for bacteria, we investigated binding of isolated S-fimbriae to glycoprotein bands on Western blot strips. Fimbriae mainly bound to a high-molecular-weight band (> 200 kD). According to molecular weight and staining behaviour, this band most likely represents mucins. We conclude that carbohydrate residues on secreted mucins of human skim milk are able to inhibit bacterial adhesion to mucosal surfaces. This could provide protection against neonatal sepsis and meningitis caused by E. coli.
Age Factors↗
[Results of zidovudine treatment of 9 vertically HIV infected children].
BACKGROUND AND METHODS: Zidovudine has been shown to be an effective antiretroviral drug in the treatment of AIDS, AIDS-related complex and also symptomatic or asymptomatic HIV infection in adults. First studies concerning zidovudine therapy in children are now available. Since 1987 we take care of HIV-infected and -exposed children at our clinic in a multicenter study. In this report we present data of a 12 months treatment period with zidovudine of 9 perinatally infected children. At enrollment the children's age ranged from 5 months to 6.8 years. The drug was given orally as capsules or syrup at a dose of 10-17 mg/kg/d every 6-8 hours. RESULTS: Zidovudine was well tolerated. Only in one case we had to reduce the dosage for a longer period of time because of hematologic abnormalities. There were no other side effects. During the study 2 patients died before the scheduled treatment regimen could be completed. In 5 children we saw a clinical improvement like weight gain, decreased hepato- and/or splenomegaly, decreased lymphadenopathy and improvement in neurologic abnormalities. The CD4+ lymphocyte counts showed a transient increase. The in vitro mitogen induced proliferation also showed a transient improvement during the first months of treatment. The p24-antigen was detected in 7/9 children. No significant changes were observed over time. CONCLUSIONS: Zidovudine can be administered safety to children with HIV infection. It is well tolerated at a dose of 10-17 mg/kg/d given every 6-8 hours. In some children clinical improvement can be observed. The immunologic and virologic improvements are only transient.
AIDS-Related Opportunistic Infections↗