Monitoring of two intravenous immunoglobulin. Preparations for immunoglobulin G subclasses and specific antibodies to bacterial surface antigens and relation with their levels in treated immunodeficient patients

Patients with antibody deficiency disorders are highly susceptible to bacterial infections. Replacement therapy with intravenous immunoglobulin preparations (IVIG) has been established in such patients for two decades. The efficacy of IVIG treatment depends on the amount of functional pathogen-specific antibodies provided. The present study was undertaken to determine the levels of immunoglobulin classes, IgG subclasses, and specific antibodies to bacterial surface antigens in two different IVIG preparations (Sandoglobulin® and Gamimmune®) and blood sera of IVIG-treated immunodeficient patients. The levels of IgG, IgA, IgM and IgG subclasses were determined in both IVIG preparations and in patients’ sera and were compared with those of healthy individuals. Sandoglobulin® contained significantly higher concentrations of IgA, IgG₂ and IgG₄ than Gamimmune®. The latter contained higher concentrations of IgG₁. Patients treated with Gamimmune® had significantly lower concentration of IgG₄ as compared with healthy individuals and Sandoglobulin®-treated patients. This finding was related to the preparation’s composition. Screening of 20 lots from each preparation for antibodies to frequent clinically isolated strains of Escherichia coli, Staphylococcus aureus, S. epidermidis, Klebsiella pneumoniae and Enterococci spp. showed a high lot-to-lot variability. In order to overcome the lot-to-lot variability and correlate the observed effects with each IVIG preparation, the administered IVIG lots were selected so that their titers were in the interval of mean value±S.D. for each pathogen. The two tested preparations showed significant differences in their content of specific antibodies that ultimately affected the levels of these antibodies in treated patients. More specifically, Sandoglobulin® contained higher levels of antibodies to E. coli and S. epidermidis strains. Infusion of this preparation maintained the respective antibodies in the recipients significantly higher than those of healthy individuals. Gamimmune® infusion led to similar and comparable levels. Both IVIG preparations had comparable antibody titers towards K. pneumoniae, provided high amounts of antibodies, and kept recipients’ specific IgG at levels significantly higher than those of the healthy individuals. Enterococci spp. specific antibodies were significantly higher in Gamimmune®, whereas titers of antibodies towards S. aureus were comparable. Levels of antibodies against both Enterococci spp. and S. epidermidis after administration of both preparations were close to those in healthy individuals. None of the patients developed infection during the time of the study. In conclusion, most of the lots of the two IVIG preparations studied, despite some quantitative differences, provide patients with sufficient amounts of antibodies to bacterial surface antigens that protect them against infections.     

Clinical and biochemical manifestations of syndrome X in obese children

The aim of this study was to investigate whether the clinical and metabolic characteristics of syndrome X had their onset in childhood in otherwise healthy but obese children of Greek origin. A group of 25 obese children and 18 age- and sex matched control subjects, aged 6–14 years, underwent an oral glucose tolerance test (OGTT), assessed for determination of plasma glucose and insulin levels. Insulin sensitivity and insulin resistance were estimated by mathematical models using calculations obtained during the OGTT. Body mass index (BMI) and blood pressure were measured, as well as serum lipoprotein and aminotransferase concentrations, after an overnight fast. The obese children had significantly higher blood pressure (systolic and diastolic) (P<0.001), triglycerides, lipoprotein(a) and alanine aminotransferase levels (P<0.05) and significantly lower HDL-cholesterol and apolipoprotein A-1 values (P<0.001). Plasma glucose levels during the OGTT were similar in both obese children and control subjects, while plasma insulin levels were significantly higher in obese children (P<0.01). In mathematical models, mean values of insulin sensitivity predictors: metabolic clearance rate and insulin sensitivity index were significantly lower in obese children (P<0.001). Predictors of beta-cell function: insulin resistance index and insulin release index were significantly higher in obese children (P<0.001). Conclusion:childhood adiposity was associated with all traditional components of syndrome X. The early recognition of these factors as predisposing elements of the appearance of metabolic syndrome requires the development of strategies to manage excess weight gain during childhood, with the ultimate goal being the prevention of type 2 diabetes and cardiovascular disease in adulthood.Abbreviations ApoA-1 apolipoprotein A-1 - ApoB apolipoprotein B - ALT alanine aminotransferase - AST aspartate aminotransferase - BMI body mass index - HDL-C HDL-cholesterol - HOMA-IR insulin resistance index - HOMA-Secr insulin release index - ISI insulin sensitivity index - LDL-C LDL-cholesterol - Lp(a) lipoprotein (a) - MCR metabolic clearance rate of glucose - OGTT oral glucose tolerance test - TC total cholesterol - TG triglycerides     

Surface tension of still wines in relation to some of their constituents: A simple determination of ethanol content

An attempt is made in this work to establish a correlation between surface tension and analytical characteristics of still wines, with the aim of predicting mainly their ethanol, protein and tannin concentrations. First, model solutions of ethanol, bovine serum albumin protein (BSA) and tannins were prepared and their surface tension measured. Second, the analytical characteristics of 20 still white and red wines from Hellenic grape varieties were determined, using methods of titration, liquid and gas chromatography (HPLC and GC/FID) and spectrophotometry (UV–vis and FTIR). For the surface tension measurements of both model solutions and wine samples, the Wilhelmy plate technique was applied. Statistical analysis of the results showed that 12 enological parameters were highly correlated with surface tension. Ethyl alcohol, proteins, tannins, potassium, sodium, total phenols and methanol, as well as the volatile acidity and pH of the wines, exhibited negative correlation; while total SO₂ and malic acid had positive correlation coefficients at a confidence level of 95%. The best linear model was obtained for the ethanol content, as it can predict by 91.4% the alcoholic strength of a wine based solely on its surface tension. This work, for the first time, provides a simple and fast way of estimating the value of such an important enological parameter.     

<Emphasis Type="Italic">TNFRSF13B/TACI</Emphasis> Alterations in Greek Patients with Antibody Deficiencies

TNFRSF13B/TACI defects have recently been associated with common variable immunodeficiency (CVID) pathogenesis. Considering that TNFRSF13B/TACI is very polymorphic and the frequency of its alterations may be different in various ethnic groups, we analyzed their prevalence in 47 Greek patients with antibody deficiencies, including CVID (16 patients), IgAD (16 patients), selective IgG4D (11 patients), and transient hypogammaglobulinemia of infancy (4 patients). A rather high frequency of TNFRSF13B/TACI defects was identified in patients with selective IgG4D (18.18%). Moreover, a patient with CVID was heterozygous in the common C104R mutation (6.25%). Both his children and a further healthy individual carried the same mutation, albeit without recurrent infections and/or hypogammaglobulinemia. The common polymorphisms V220A and P251L were identified in all disease subgroups, in an almost similar frequency with that observed in 259 healthy controls. Our data provide further evidence that TNFRSF13B/TACI alterations are not causative of CVID. Possibly, they predispose to humoral deficiencies and/or contribute to their phenotype when combined with other immune gene alterations.     

Association of interleukin-1A, interleukin-1B and interleukin-1 receptor antagonist gene polymorphisms with multiple myeloma

Interleukin-1 (IL-1) is a cytokine involved in the maturation and proliferation of B cells and plays a significant role in the development of lytic bone lesions, a major clinical feature of multiple myeloma (MM) patients. Genes that regulate products involved in the immune system are highly polymorphic and contribute to inter-individual differences that can influence the genetic predisposition and progression of particular diseases and cancers. In this study, we investigated the correlation between the single nucleotide polymorphisms IL1A -889, IL1B -511, IL1B +3954, IL1RN Mspa1 +11100 and susceptibility to MM in 74 patients and 160 controls. We found that individuals possessing IL1A -889 CT polymorphism had a higher risk in developing MM. Moreover, genotypes IL1B -511 CC, IL1B +3954 CC, IL-1RN Mspa1 +11100 CC and the combination of IL 1B +3954 CC with IL1B -511 CC or IL-1RN Mspa1 +11100 CC exerted a protective effect in individuals possessing them.     

Evaluation of different PCR assays for early detection of acute and relapsing brucellosis in humans in comparison with conventional methods

Human brucellosis is a significant public health problem in many Mediterranean countries including Greece. The conventional serological methods, as well as blood cultures, have serious limitations, especially in chronic, relapsing, and focal forms of the disease. Four different PCR assays were applied in 4,926 buffy coat, whole-blood, and serum samples received from 200 patients admitted with brucellosis to the Infectious Diseases Hospital, Thessaloniki, Greece, for the rapid diagnosis of acute infection and relapses and compared to blood culture and serological tests (i.e., Wright's seroagglutination test, Coombs' antibrucella test, and the complement fixation test). The four PCR assays had excellent sensitivity and specificity and were able to detect all of the cases of acute disease. Buffy coat and whole blood were the optimal specimens. All four PCR assays were negative in all follow-up samples from 183 patients who had completed a successful treatment and were positive in all follow-up samples from 17 patients who had relapses in the first year after therapy, including the times of the relapses. In conclusion, PCR is a very useful tool for the rapid diagnosis of acute brucellosis and a good marker for the posttreatment follow-up and the early detection of relapses.     

Prevalence of selective immunoglobulin A deficiency in Greek children and adolescents with type 1 diabetes

Background

The association of selective immunoglobulin A (IgA) deficiency with type 1 diabetes (T1D) remains unclear. This study was to evaluate serum IgA concentrations in Greek children and adolescents with T1D.

Methods

In two hundred individuals with T1D, serum IgA concentrations were quantitatively determined using nephelometry.

Results

Immunoglobulin A deficiency was detected in 6 (3.0%) of 200 patients who were subjected to immunological evaluation. Recurrent infections were not recorded, but human papilloma virus infection was clinically suspected and confirmed by laboratory examination in a 5-year-old girl. In regard to coincidence of selective IgA deficiency with autoimmune diseases, celiac disease was detected in a girl and juvenile idiopathic arthritis in a boy. Serum IgA concentrations differed significantly when patients were grouped according to age at the beginning of the study (P<0.001), age at diagnosis of T1D (P=0.015) and coincidence of celiac disease (CD) (P=0.038). However, when the age of the patients was adjusted, difference in serum IgA concentrations was not statistically significant despite CD was present or not. Moreover, serum IgA concentrations were positively correlated with serum IgG (P<0.001) and IgE (P=0.001) concentrations and negatively correlated with serum antigliadin antibody IgG (P=0.035) concentrations. There was no association or correlation of serum IgA concentrations with glycemic control.

Conclusion

The prevalence of selective IgA deficiency in Greek children and adolescents with T1D is high (3.0%). The correlation of serum IgA concentrations with serum IgG, IgE and anti-gliadin antibody IgG concentrations needs further investigation.

     

Total antioxidant status in patients with obstructive sleep apnea without comorbidities: the role of the severity of the disease

Objective  

Several studies suggest that obstructive sleep apnea syndrome (OSAS) is associated with oxidative stress. However, there are also contrary observations and the role of antioxidant mechanisms has not been fully explored.     

Correlation of matrix metalloproteinase levels with the grade of proliferative vitreoretinopathy in the subretinal fluid and vitreous during rhegmatogenous retinal detachment

Purpose: We investigated the activity of matrix metalloproteinase (MMP)‐2 and ‐9 and their latent pro‐forms (proMMP‐2, ‐9), and protein levels of MMP‐1, ‐3, ‐8 and tissue inhibitor of MMPs (TIMP)‐1 in the subretinal fluid (SRF) and vitreous of patients with rhegmatogenous retinal detachment (RRD). Potential correlations with proliferative vitreoretinopathy (PVR) grade were determined. Methods: Thirty‐seven SRF and 32 vitreous samples from RRD patients and nine vitreous samples from human organ donors (controls), were collected and assayed for MMP‐1, ‐3, ‐8/TIMP‐1 levels using enzyme‐linked immunosorbent assay (ELISA), and for proMMP‐2, ‐9, MMP‐2, ‐9 activity employing gelatine zymography. Results: ProMMP‐2, ‐9, MMP‐1, ‐3, ‐9, TIMP‐1 were significantly higher in the SRF and vitreous of RRD patients compared to the vitreous of organ donors. MMP‐8 levels were higher in RRD patients’ SRF. Regarding PVR grade, MMPs and TIMP‐1 were differentially present in SRF and vitreous. PVR grade correlated significantly with the levels of MMP‐2 in SRF, while proMMP‐2, MMP‐1, ‐2, ‐3, ‐8, ‐9 and TIMP‐1 levels correlated with PVR grade in the vitreous. Conclusion: MMP/TIMP‐1 levels are elevated in SRF and vitreous during RRD. Significant correlations between PVR grade and MMP‐2 in SRF and proMMP‐2, MMP‐1, ‐2, ‐3, ‐8, ‐9 and TIMP‐1 levels in vitreous were revealed. Investigation of MMP activity in vitreous may provide more valid conclusions compared to SRF pertaining to the role of the MMPs during RRD. The observations of the present study suggest a possible role for MMPs and TIMP‐1 in PVR pathophysiology.