Der p 23 sensitisation in patients with house dust mite respiratory allergy.

Summary: Background. The sensitization profile of patients allergic to house dust mites (HDM) and its molecular diagnosis may determine treatment and evolution of the disease. The present study investigates the prevalence of Der p 23 sensitization and its relation to asthma in a population of HDM-allergic patients. Methods. We conducted a cross-sectional study of 891 patients with HDM allergy with symptoms of rhinitis and 52.1% of them with asthma. Total and specific IgE (sIgE) was measured against Dermatophagoides pteronyssinus and its molecular components (Der p 1, Der p 2 and Der p 23) and the storage mite Lepidoglyphus destructor using ImmunoCAP. Prevalence of sensitization and levels of sIgE were analysed according to asthma diagnosis and asthma severity. Results. Der p 23 was the predominant allergen in this population (83.7%) but IgE levels were lower than those of sIgE to Der p 1 and Der p 2. A good correlation was found between sIgE to Der p 23 and the other allergens. A total of 8.2% patients were monosensitized to Der p 23. Asthma was more frequent in patients with positive sIgE against Der p 23 than in patients without this sensitization (52.8% vs 42.8%, p = 0.027). A tendency to increase both total IgE and sIgE was observed in relation to the severity of asthma from intermittent mild asthma to persistent moderate asthma but a substantial decrease in total IgE and sIgE was detected in more severe asthmatics. Conclusions. Der p 23 might be a prevalent allergen in regions with high rates of HDM exposure. Even though sIgE levels against this allergen are usually low, its presence could increase the risk of asthma.

Anaphylaxis to Vespa velutina nigrithorax: Pattern of Sensitization for an Emerging Problem in Western Countries.

OBJECTIVE: To define the sensitization pattern of patients with anaphylaxis to Vespa velutina nigrithorax (VVN). METHODS: We studied 100 consecutive Spanish patients with anaphylaxis to Hymenoptera venom and systematically determined specific IgE (sIgE) to whole venoms (Vespula species, Polistes dominula, Apis mellifera, Vespa crabro, and Dolichovespula maculata) and their molecular components (rApi m 1, rApi m 5, rApi m 10, rVes v 1, rVes v 5, rPol d 5, and cross-reactive carbohydrates). Specific IgE to VVN venom and its antigen 5 (nVesp v 5) were measured in a subsample. RESULTS: Seventy-seven patients had anaphylaxis to VVN. Of these, only 16 (20.8%) reported previous VVN stings, but were stung by other Hymenoptera. Positive sIgE (>0.35 kUA/L) to each of the whole venoms was detected in >70% of patients (Vespula species in 100%). The components showing >50% positivity were rApi m 5 (51.4%), rPol d 5 (80.0%), and rVes v 5 (98.7%). This pattern was similar to that of Vespula species anaphylaxis (n=11) but different from that of A mellifera anaphylaxis (n=10). Specific IgE to nVesp v 5 was positive in all patients (n=15) with VVN anaphylaxis and was correlated with sIgE to both rVes v 5 (R=0.931) and rPol d 5 (R=0.887). CONCLUSIONS: VVN has become the commonest cause of Hymenoptera anaphylaxis in our area. Most cases report no previous VVN stings. Their sensitization pattern is similar to that of patients with anaphylaxis to other Vespidae. Specific IgE to antigen-5 from VVN, Vespula species, and P dominula are strongly correlated in patients with VVN anaphylaxis.

Association Between Asthma and Sensitization to Allergens of Dermatophagoides pteronyssinus.

BACKGROUND AND OBJECTIVE: Little is known about the role of molecular diagnosis in house dust mite (HDM) allergy. In this study, we investigated the association between the sensitization profile of adolescent and adult HDM-allergic patients and asthma in a region with high rates of exposure to HDM. METHODS: We conducted a cross-sectional study of 384 HDM-allergic patients (38.5%, males; median age, 28 years). A total of 368 patients (95.8%) had rhinitis, and 175 (45.6%) had asthma. Specific IgE (sIgE) to Dermatophagoides pteronyssinus, nDer p 1, rDer p 2, and rPen a 1 was measured in all patients. sIgE to Lepidoglyphus destructor was measured in patients (n=301) with a positive skin test result. RESULTS: Significantly higher concentrations of sIgE to Der p 1 and sIgE to Der p 2 were observed in patients with asthma than in those without asthma. The proportion of asthmatic patients was higher among individuals who reacted (≥0.35 kUA/L) to both Der p 1 and Der p 2 (147/291, 50.5%) than among those who reacted to only 1 allergen (either Der p 1 or Der p 2, 18/55, 32.7%) or neither allergen (10/38, 26.3%, P=.002). Reactivity to both allergens was associated with asthma after adjusting for age and sex (OR, 2.87; 95%CI, 1.32-6.20). Higher concentrations of sIgE to L destructor were observed in patients with asthma than in patients without asthma. Tropomyosin sIgE ≥0.35 kUA/L was detected in only 6 individuals (1.6%). CONCLUSIONS: L destructor may be a relevant allergen in high-exposure areas. Dual sensitization (ie, IgE to both Der p 1 and Der p 2) may help to identify HDM-allergic patients who are at risk of asthma.

Serum levels of keratin-18 fragments [tissue polypeptide-specific antigen (TPS)] are correlated with hepatocyte apoptosis in alcoholic hepatitis.

Apoptosis is a major feature in alcoholic hepatitis. During apoptosis, the M30 neoepitope becomes exposed after keratin-18 cleavage. The tissue polypeptide-specific antigen (TPS) is a keratin-18 fragment that is routinely used as a tumor marker. Serum TPS levels are increased in patients with alcoholic hepatitis. The aim of this study was to investigate the possible relationship of TPS levels with hepatocyte apoptosis in alcoholic hepatitis. Thirty-one patients with alcoholic hepatitis and 22 with fatty liver were included. Hepatocyte apoptosis was evaluated by M30 immunostaining. Serum TPS levels were measured by a commercial immunoassay. The apoptotic score was higher in patients with alcoholic hepatitis than in patients with fatty liver. There was a significant correlation between the apoptotic score and TPS levels. The correlation of the apoptotic score with TPS levels was stronger than with standard liver tests. Serum TPS may be a marker of apoptosis in alcoholic hepatitis.

Sensitization to cross-reactive carbohydrate determinants in relation to alcohol consumption.

BACKGROUND: Alcohol consumption is associated with increased serum IgE of unknown specificity. OBJECTIVE: To investigate the prevalence of specific IgE to cross-reactive carbohydrate determinants (CCDs) in adults, and its relation to alcohol consumption. METHODS: Population-based survey of 457 adults (218 abstainers, 195 light-to-moderate drinkers, 44 heavy drinkers). Specific IgE determinations included a CCD (MUXF(3), the N-glycan of bromelain), pollens (Lolium perenne and Olea europaea), Hymenoptera venoms (Apis mellifera and Vespula spp.), and a mite (Dermatophagoides pteronyssinus). We replicated these studies in an additional sample of alcoholics (n=138). Inhibition assays were performed in selected cases. RESULTS: In the general population, 5.6% of individuals (95% confidence interval 3.5-7.6%) showed positive (>/=0.35 kU/L) CCD-specific IgE. The levels of CCD-specific IgE were particularly high in heavy drinkers, who also showed a high prevalence of positive IgE to pollens and Hymenoptera venoms, doubling (at least) the prevalence found in alcohol abstainers and light-to-moderate drinkers. The presence of IgE to pollens and Hymenoptera venoms was closely correlated with the presence of CCD-specific IgE. These features were confirmed in the additional sample of alcoholics. Inhibition studies indicated a role of CCD interference in IgE positivity to pollen and Hymenoptera allergens in alcoholics. CONCLUSIONS: CCD-specific IgE is prevalent in heavy drinkers, and is associated with positive IgE to pollens and Hymenoptera venoms. Specific IgE results should be interpreted with caution in heavy drinkers.

Evaluation of the phadiatop test in the diagnosis of allergic sensitization in a general adult population.

BACKGROUND: Phadiatop is a commercially available qualitative serological test employed for screening of allergic sensitization in patients with suspected allergic diseases. AIM: The study evaluated the diagnostic accuracy of Phadiatop for the diagnosis of allergic sensitization in a general adult population. METHODS: A total of 469 subjects from the population of A-Estrada (Spain) were selected by age-stratified random sampling (age range, 18-92 years). Phadiatop test (Uni-CAP method) was performed in serum samples from 465 of these subjects. Skin prick tests to a panel of 13 relevant aeroallergens in the studied area (including mites, pollens, moulds, and animal dander) were employed as the reference diagnostic procedure. Subjects with at least a positive skin prick test (> or =4 mm, n= 120) were considered to have allergic sensitization. RESULTS: Phadiatop sensitivity was 70.8% (95% CI 61.7-78.6%), specificity 90.7% (95% CI 87.0-93.5%), positive predictive value 72.6% (95% CI 63.5-80.3%), negative predictive value 89.9% (95% CI 86.2-92.8%), global accuracy 85.6% (95% CI 82.0-88.6%), negative likelihood ratio 0.3 (95% CI 0.2-0.4), and positive likelihood ratio 7.6 (95% CI 5.4-10.8). A high proportion of false-positive Phadiatop cases showed (a) increased total serum IgE levels, (b) significant alcohol consumption, and (c) small-sized (below the diagnostic cut-off) wheal reactions on SPT. A high proportion of false-negative Phadiatop cases showed exclusive storage mite sensitization. Sensitivity and positive predictive value of Phadiatop were somewhat higher among individuals with a history of nasal or bronchial symptoms. CONCLUSIONS: Phadiatop is a valuable tool for the diagnosis of allergic sensitization in a general adult population. However, limitations of the test should be taken into account in similar surveys.

Effects of long-term treatment with antiepileptic drugs on serum lipid levels in children with epilepsy.

We determined serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and triglycerides (TGs) in 125 healthy children and in 119 children with epilepsy who had been receiving carbamazepine (58 children), phenobarbital (22 children), or valproic acid (39 children) for 7 months to 10.5 years (mean, 5.8 years). None of the variables considered was significantly correlated with time elapsed since start of treatment or with drug concentration in serum. In the groups receiving carbamazepine or phenobarbital, mean TC, HDL-C, and LDL-C levels were higher than in the control group, the differences being statistically significant for all except LDL-C in the phenobarbital group. In neither group did mean TC/HDL-C ratio or mean LDL-C/HDL-C ratio differ significantly from the corresponding control-group mean. In the group receiving valproic acid, mean TC level, mean LDL-C level, mean TC/HDL-C ratio, and mean LDL-C/HDL-C ratio were significantly lower than in the control group. In none of the treated groups did mean VLDL-C or TG level differ significantly from the corresponding control-group mean. Our results suggest, in contrast to previous reports, that the effects on the serum lipid profile of long-term treatment with hepatic-enzyme-inducing antiepileptic drugs (such as carbamazepine and phenobarbital) are probably not beneficial as regards risk of atherosclerosis-related disease. Our results additionally suggest a need for careful monitoring of serum cholesterol levels in children with epilepsy receiving carbamazepine or phenobarbital.

Differences between men and women as regards the effects of protein-energy malnutrition on the hypothalamic-pituitary-gonadal axis.

Although protein-energy malnutrition (PEM) affects 50% of hospitalized patients, its effects on the hypothalamic-pituitary-gonadal (HPG) axis have not been extensively investigated. To investigate the effects of PEM on the HPG axis in hospitalized patients, 62 inpatients ages 18-91 y (35 men and 27 women) had a nutritional and hormonal evaluation. Hormones were determined in blood samples obtained between 0700 and 1200 h. Patients were divided into two subgroups: those with body mass index (BMI) <18.5 kg/m2 (low body mass index [LBMI]; 16 men, 13 women) and those with BMI >20 kg/m2 (normal-high body mass index [NHBMI]; 19 men, 14 women). The nutritional parameters of LBMI patients were inferior to those of NHBMI patients. Total and free testosterone levels were subnormal, 31.4% and 17.2% respectively, in all men; free testosterone was subnormal in 31.25% of LBMI versus 5.3% of NHBMI male patients and total testosterone concentration was subnormal in 43.8% of LBMI versus 21.1% of NHBMI male patients. Luteinizing hormone (LH) level was higher in LBMI men than in NHBMI men, whereas the reverse was the case for women, for whom follicle-stimulating hormone (FSH) also was lower in the LBMI group than the NHBMI group. The HPG axis hormones which best discriminated between the LBMI and NHBMI groups were free testosterone for men and LH and FSH for women, which were all lower in the LBMI than in the NHBMI group. LH was correlated with BMI and midupper arm muscle circumference (AMC) (women positively and men negatively) but not with triceps skin-fold thickness (TSF). Total testosterone level was positively correlated with AMC and free testosterone with TSF. Hypogonadism is common among hospitalized patients with PEM. Men with PEM have low testosterone levels with normal or high gonadotropin levels, which suggests impairment of Leydig cell function. Women with PEM suffer hypogonadotropic hypogonadism. AMC correlates positively with total serum testosterone concentration in men and with LH levels in women, suggesting that satisfactory function of the HPG axis requires a functional (protein) reserve as well as an energy (fat) reserve.

Purine metabolites and pyrimidine bases in cerebrospinal fluid of children with simple febrile seizures.

Adenosine monophosphate, inosine monophosphate, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine, uric acid and pyrimidine bases were determined in the CSF of 18 children after simple febrile seizures and in a control group. There was no statistically significant difference between the two groups for any of these metabolites. This suggests that simple febrile seizures neither significantly disturb the metabolism of nucleotides, nucleosides or bases, nor significantly deplete neuron adenosine triphosphate ATP levels.

Concentrations of purine nucleotides and purine and pyrimidine bases in cerebrospinal fluid of neurologically healthy children.

The concentrations of the nucleotides AMP and IMP, the nucleosides adenosine, guanosine and inosine, the purine bases adenine, guanine, hypoxanthine and xanthine, urate, and the pyrimidine bases cytosine, thymine and uracil were determined by high performance liquid chromatography in the cerebrospinal fluid of 63 children aged between 1 month and 13 years who showed no sign of neurological disease. The results are compared with those of other authors, and used to establish reference ranges for the above metabolites in the cerebrospinal fluid of children.

Concentrations of nucleotides, nucleosides, purine bases and urate in cerebrospinal fluid of children with meningitis.

The release of agents mediating inflammation in meningitis may bring about neuronal hypoxia, under which circumstances ATP concentrations decrease and its degradation products increase and are released into the cerebrospinal fluid. In this study of alterations in neuronal energy metabolism in meningitis, AMP, IMP, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine and urate were determined by high performance liquid chromatography in the cerebrospinal fluid of 54 children aged between 1 month and 13 years suffering from meningitis (25 viral, 24 bacterial and 5 tuberculous cases) and 63 controls. Compared to the controls, patients with viral meningitis exhibited high concentrations of IMP, adenosine, guanosine, adenine, guanine and xanthine; patients with bacterial meningitis exhibited high concentrations of IMP, inosine, guanosine, adenosine, hypoxanthine, xanthine and urate; and patients with tuberculous meningitis exhibited high concentrations of AMP, guanosine, xanthine and urate. Viral and bacterial cases did not differ significantly for any of the metabolites studied. AMP and urate concentrations were significantly higher in patients with tuberculous cases compared with viral or bacterial meningitis cases.

C-C chemokines in the vitreous of patients with proliferative vitreoretinopathy and proliferative diabetic retinopathy.

PURPOSE: To investigate the presence of three C-C chemokines (monocyte chemotactic protein-1 [MCP-1], macrophage inflammatory protein-1alpha [MIP-1alpha], and MIP-1beta) in vitreous samples from eyes with proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR), or retinal detachment (RD). SUBJECTS AND METHODS: Vitreous samples were obtained and assayed by solid phase enzyme-linked immunosorbent assay for the chemokines MCP-1, MIP-1alpha, and MIP-1beta in a prospective study of 43 consecutive patients. Eighteen samples from cadaveric control eyes were also assayed. RESULTS: Monocyte chemotactic protein-1 was detected in all samples. The vitreous of eyes with vitreoretinal disorders showed significantly higher levels than the vitreous of cadaveric control eyes (P < or = 0.05). Median level (5th-95th percentile) in the PVR cases (n = 20) was 890.18 pg/mL (286.04-1806.20); in RD (n = 8), 296.69 pg/mL (171.44-1310.02); and in PDR (n = 15), 434.60 pg/mL (124.56-1092.94). In the cadaveric control eyes (n = 18), median level was 83.97 pg/mL (26.09-208.38). Macrophage inflammatory protein-1alpha and MIP-1beta were not detected in any samples. CONCLUSION: Monocyte chemotactic protein-1 might be involved in the recruitment of macrophages and monocytes into the vitreous of eyes with proliferative vitreoretinal disorders.

Effects of various serum proteins on quantification of fructosamine.

We determined fructosamine concentrations with the CentrifiChem 600 centrifugal analyzer and the Hitachi 737 discrete analyzer. Reference intervals agreed with the most recently published results, and values in fasting patients were significantly correlated with glycated hemoglobin, plasma glucose, albumin, beta- and gamma-globulins, IgG, IgA, IgM, and total protein. Partial correlation analysis showed that only fructosamine and IgA were dependently related. In a group of nondiabetic patients with pathological values for IgA concentrations, 79.4% had pathological values for fructosamine. These results throw doubt on the clinical value of fructosamine determinations if serum IgA is not taken into account.

Influence of acute alcohol intake and alcohol withdrawal on circulating levels of IL-6, IL-8, IL-10 and IL-12.

Cytokine balance alterations are responsible for some of the systemic and hepatic manifestations of alcoholism. The present study was aimed to evaluate the influence of both acute alcohol abstinence (in alcoholics) and acute alcohol intake (in healthy subjects) on serum IL-6, IL-8, IL-10, and IL-12 levels. Serum cytokine concentrations were determined on admission and after a median of 6 days of ethanol abstinence in 29 patients with alcohol withdrawal syndrome. The same determinations were made in five healthy volunteers at baseline and after 36 h of a single 60 g-dose alcohol intake. Increased serum levels of IL-6, IL-10 and, to a lesser extent IL-8, declined in the few days after alcohol abstinence in patients with alcohol withdrawal syndrome. Serum IL-8 values increased after alcohol intake in healthy subjects. Rapid variation of serum cytokine levels along with alcohol intake or abstinence should be taken into account in cytokine studies in alcohol abusers.

Increased serum tissue polypeptide specific antigen (TPS) in alcoholics: a possible marker of alcoholic hepatitis.

BACKGROUND: Serum tissue polypeptide specific antigen (TPS) is widely used as a tumor proliferation marker. There is some evidence of an increase in serum TPS in benign liver diseases. The aim of the study was to evaluate serum TPS levels in alcoholics. METHODS: Seventy-seven alcoholics (64 men and 13 women) admitted to the hospital with ethanol withdrawal syndrome entered the study. Twenty-three patients were biopsied (12 of them had alcoholic hepatitis and 11 steatosis or fibrosteatosis). Serum TPS was determined by enzyme immunoassay in all cases. Results were compared with those of 24 healthy controls. RESULTS: Serum TPS levels were significantly increased in alcoholic patients compared with controls (median 365 units/liter and range 41-6400 units/liter versus median 79 units/liter and range 19-235 units/ liter, respectively, p < 0.0001). Seventeen alcoholics (22%) had a TPS value 10 times higher than the upper normal threshold level (> or = 1000 units/liter). Among alcoholics, serum TPS levels were higher in patients with alcoholic hepatitis than in those with steatosis or fibrosteatosis (median 1486 units/liter and range 176-5023 units/liter versus median 106 units/liter and range 41-221 units/liter, respectively, p = 0.0001), offering a better discriminant value for the diagnosis of alcoholic hepatitis than usual liver function parameters. Serum TPS values showed significant correlation with liver cell necrosis and Mallory's hyaline degeneration. TPS values decreased after alcohol abstinence during hospital admission. CONCLUSIONS: Serum TPS is frequently increased in alcoholics and may be a marker of alcoholic hepatitis. Specificity of this molecule as a tumor marker is limited in alcoholics.

High serum IgA concentrations in patients with diabetes mellitus: agewise distribution and relation to chronic complications.

In this study we investigated the agewise distributions of serum IgA concentrations in 1251 type 1 and 2224 type 2 diabetic patients, and the association between serum IgA concentration and diabetic complications (retinopathy, neuropathy, nephropathy, macroangiopathy, and hypertension). The IgA concentrations of all groups of diabetic patients were significantly higher than those of the corresponding subgroups of 943 control subjects, except for type 1 patients >60 years of age. High IgA concentrations were found in 23.1% of the whole diabetic group. The prevalence of high IgA was significantly greater in males than in females among type 1 patients (24.4% vs 18%). In conclusion, an increase in circulating IgA concentrations is a generalized phenomenon among diabetic patients; IgA concentrations above the reference range are more common among male than female diabetics; and diabetic complications are associated with a significant increase in serum IgA concentration.

Effects of chronic allopurinol therapy on purine metabolism in Duchenne muscular dystrophy.

Adenine, adenosine, inosine, hypoxanthine, xanthosine, xanthine, guanine and guanosine blood levels in 11 Duchenne muscular dystrophy patients treated with allopurinol, 10 untreated patients and 8 healthy controls, were determined by HPLC. Serum ADA, PNP and 5'-NT were also determined. Untreated patients showed lower adenine (p less than 0.001) and higher adenosine, xanthine, ADA and PNP levels (p less than 0.01) than controls. Treated patients had lower adenine and higher xanthine levels (p less than 0.001), but higher hypoxanthine, xanthosine and guanine levels (p less than 0.001), than controls, with normal ADA and PNP. The changes observed in ADA and PNP levels suggest an involvement of these enzymes in accelerated degradation of purines in Duchenne dystrophy.

The concentrations of xanthine and hypoxanthine in cerebrospinal fluid as therapeutic guides in hydrocephalus.

Xanthine, hypoxanthine, and total oxypurine levels were determined in the cerebrospinal fluid of 18 hydrocephalic patients and 8 healthy controls by high-performance liquid chromatography (HPLC). Eight of the hydrocephalic patients were self-compensated and 10 had shunts implanted during the course of the study. The mean xanthine, hypoxanthine, and total oxypurine levels in the normal children were 5.20, 5.94 and 11.29 mumol/l, respectively. In self-compensated hydrocephalics these levels were respectively 6.06, 6.50 and 12.57 mumol/l. In noncompensated hydrocephalics, they were 11.40, 10.79 and 22.19 mumol/l. The differences between the latter group and the first two are statistically significant (P less than 0.001). Fifteen days after implantation of shunts in the noncompensated hydrocephalics, the mean xanthine levels had fallen to 4.61 mumol/l, the mean hypoxanthine levels to 5.03 mumol/l, and the mean total oxypurine levels to 9.64 mumol/l. The change is statistically significant (P less than 0.001). In light of these findings we propose that xanthine, hypoxanthine, and total oxypurine levels be used in cases of hydrocephalus as guides for therapeutic action and to monitor progress.

Serum cytokines and increased total serum IgE in alcoholics.

BACKGROUND: It has been reported that total serum IgE is increased in alcohol abusers, but the mechanisms responsible are not known. Production of IgE depends on B-cell stimulation by both antigens and some cytokines, particularly IL-4 and IL-13. Chronic alcoholism and alcoholic liver disease are accompanied by changes in cytokine production. AIM OF THE STUDY: To evaluate if IgE increase in alcoholics could be associated to a ethanol-induced imbalance of the cytokine profile. PATIENTS AND METHODS: A total of 65 patients (53 males and 12 females, aged 47 +/- 12 years), admitted to the hospital because of ethanol abstinence symptoms entered the study. On admission, total serum IgE was measured by chemiluminescent EIA and serum IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, and interferon-gamma were measured by ELISA. Data were compared with those of 40 healthy control subjects. RESULTS: Serum IgE, IL-6, IL-8, IL-10, IL-12, and IL-13 were found to be high in alcoholic patients compared with healthy volunteers. Some parallelism was observed between serum IgE and both serum IL-10 and IL-13 were increased in alcoholics. CONCLUSIONS: Total serum IgE elevation in alcoholics with abstinence syndrome is accompanied by an increase of some type 2 cytokines. Ethanol-induced alterations in the cytokine profile may contribute to increased IgE levels in alcoholics.