Optimization of the therapy of atopic dermatitis by means of immunotherapy

Taking into account disturbances in the functioning of the immune system in atopic dermatitis (AD) and the potentiating role of staphylococcal and other infections, the possibility of the optimization of the therapy of AD with the use of preparations having immunomodulating action and immunogenic activity is proposed. In the complex therapy of AD in children we used polycomponent vaccine Immunovac B-4, introduced intranasally and orally. Under the influence of immunotherapy the clinical characteristics of the patients had pronounced positive dynamics. A considerable decrease in the spread of the process, the degree of its severity and subjective symptoms was noted shortly after the course of vaccine treatment. Simultaneously the SCORAD index dropped from 64.5 to 39.4. During the later period of observation further decrease in the severity of the course of AD in children occurred, and the minimal characteristics were observed in 6 months of observation. At that time the SCORAD index fell to 19.9 +/- 1.34. The volume of pharmacotherapy and the number of acute respiratory infections considerably decreased, the positive dynamics of the quantitative and qualitative composition of the intestinal microflora was noted. The prolonged immunotherapeutic effect of the polycomponent vaccine made it possible to recommend the vaccine for the optimization of the therapy of AD.     

Strategies of adaptation: interpopulation selection differentials

Spatial and temporal variation of selection intensities has been analyzed using published data on Crow's indices in 278 human populations, representing various anthropological types, religions, cultures and a wide spectrum of environmental conditions. Statistical analysis has shown that populations with different types of economy have different adaptive strategies. In tribal populations both components of selection-differential fertility and differential mortality-have equal contributions, vary according to ecological factors and show no decline with time. Urban populations of the industrially developed countries show dramatic selection relaxation; the second component becomes negligible due to a sharp decrease in childhood mortality; fertility and its variance are reducing due to cultural factors (family planning).     

Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis

Antibodies to citrullinated proteins (anti-cyclic-citrullinated peptide [anti-CCP] antibodies) are highly specific for rheumatoid arthritis (RA) and precede the onset of disease symptoms, indicating a pathogenetic role for these antibodies in RA. We recently showed that distinct genetic risk factors are associated with either anti-CCP-positive disease or anti-CCP-negative disease. These data are important as they indicate that distinct pathogenic mechanisms are underlying anti-CCP-positive disease or anti-CCP-negative disease. Likewise, these observations raise the question of whether anti-CCP-positive RA and anti-CCP-negative RA are clinically different disease entities. We therefore investigated whether RA patients with anti-CCP antibodies have a different clinical presentation and disease course compared with patients without these autoantibodies. In a cohort of 454 incident patients with RA, 228 patients were anti-CCP-positive and 226 patients were anti-CCP-negative. The early symptoms, tender and swollen joint count, and C-reactive protein level at inclusion, as well as the swollen joint count and radiological destruction during 4 years of follow-up, were compared for the two groups. There were no differences in morning stiffness, type, location and distribution of early symptoms, patients' rated disease activity and C-reactive protein at inclusion between RA patients with and without anti-CCP antibodies. The mean tender and swollen joint count for the different joints at inclusion was similar. At follow-up, patients with anti-CCP antibodies had more swollen joints and more severe radiological destruction. Nevertheless, the distribution of affected joints, for swelling, bone erosions and joint space narrowing, was similar. In conclusion, the phenotype of RA patients with or without anti-CCP antibodies is similar with respect to clinical presentation but differs with respect to disease course.     

Design of reference populations for genomic selection in crossbreeding programs

Background

In crossbreeding programs, genomic selection offers the opportunity to make efficient use of information on crossbred (CB) individuals in the selection of purebred (PB) candidates. In such programs, reference populations often contain genotyped PB animals, although the breeding objective is usually more focused on CB performance. The question is what would be the benefit of including a larger proportion of CB individuals in the reference population.

Methods

In a deterministic simulation study, we evaluated the benefit of including various proportions of CB animals in a reference population for genomic selection of PB animals in a crossbreeding program. We used a pig breeding scheme with selection for a moderately heritable trait and a size of 6000 for the reference population.

Results

Applying genomic selection to improve the performance of CB individuals, with a genetic correlation between PB and CB performance (r_PC) of 0.7, selection accuracy of PB candidates increased from 0.49 to 0.52 if the reference population consisted of PB individuals, it increased to 0.55 if the reference population consisted of the same number of CB individuals, and to 0.60 if the size of the CB reference population was twice that of the reference population for each PB line. The advantage of using CB rather than PB individuals increased linearly with the proportion of CB individuals in the reference population. This advantage disappeared quickly if r_PC was higher or if the breeding objective put some emphasis on PB performance. The benefit of adding CB individuals to an existing PB reference population was limited for high r_PC.

Conclusions

Using CB rather than PB individuals in a reference population for genomic selection can provide substantial advantages, but only when correlations between PB and CB performances are not high and PB performance is not part of the breeding objective.     

Complex of recombinant heat shock protein with lipopolysaccharide induces rapid protection of mice against Salmonella typhimurium and avirulent for humans avian influenza virus H5N2

Protective effect of immunization with heat shock protein (HSP) against bacterial and viral infections in mice was studied. Recombinant HSP 70 kDa of Mycobacterium tuberculosis contaminated with lypopolysaccharide (0.185 mcg/ml) was used for experiments. One intraperitoneal injection of 100 or 400 mcg of HSP induced rapid protection against intraperitoneal challen e with 125 LD50 of Salmonella typhimurium (on 3rd-6th day) and against intranasal challenge with 10 LD50 of avirulent for humans avian influenza virus H5N2 (A/ mallard/Pennsylvania/10218/84) (on 5th-8th day). Three daily injections with 10 mcg of HSP induced rapid, significant and long-term protection against S. typhimurium. Immunization with HSP protected 100% of mice during 3 days after the challenge, 50% of immunized animals survived during 21 days (duration of the study). All nonimmunized mice died on 6th day.     

Development of a zooplankton community including <Emphasis Type="Italic">Heterocope saliens</Emphasis> Lillijeborg in an experiment with hydrophytes

The influence of the submerged plants Ceratophyllum demersum L. and Elodea canadensis Michx. and the floating plant Hydrocharis morsus-ranae L. on the species composition and quantitative parameters of a zooplankton community was studied experimentally. Among submerged vegetation, the development of the predaceous calanid Heterocope saliens Lilljeborg was suppressed. An increase in the number of zooplankter species was observed in all experimental ecosystems with hydrophytes. The species similarity of zooplankton was higher between communities with plants of the same ecological group than with plants of different groups. The highest average zooplankton biomass, as determined by the abundance of Daphnia longispina O.F. Müller and Simocephalus vetulus (O.F. Müller), was observed in experiments with Elodea. The highest average abundance over the experimental period was recorded among Ceratophyllum, where the abundance of Rotifera, chydorids, and copepods common in hydrophyte beds was higher than in other versions of the experiment.     

Anti-citrullinated fibronectin antibodies in rheumatoid arthritis are associated with human leukocyte antigen-DRB1 shared epitope alleles

Introduction

Fibronectin is one of the most abundant proteins present in the inflamed joint. Here, we characterized the citrullination of fibronectin in the joints of rheumatoid arthritis (RA) patients and studied the prevalence, epitope specificity and human leukocyte antigen (HLA) association of autoantibodies against citrullinated fibronectin in RA.

Methods

Citrullinated residues in fibronectin isolated from RA patient synovial fluid were identified by mass spectrometry. The corresponding citrullinated and non-citrullinated peptides were synthesized and used to analyze the presence of autoantibodies to these peptides in RA sera and sera from other diseases and healthy controls by ELISA. The data were compared with risk factors like shared epitope HLA alleles and smoking, and with clinical features.

Results

Five citrullinated residues were identified in fibronectin from RA synovial fluid. RA sera reacted in a citrulline-dependent manner with two out of four citrullinated fibronectin peptides, one of which contains two adjacent citrulline residues, in contrast to non-RA sera, which were not reactive. The most frequently recognized peptide (FN-Cit_1035,1036, LTVGLTXXGQPRQY, in which × represents citrulline) was primarily targeted by anti-CCP (cyclic citrullinated peptide) 2-positive RA patients. Anti-FN-Cit_1035,1036 autoantibodies were detected in 50% of established anti-CCP2-positive RA patients and in 45% of such patients from a early arthritis clinic. These antibodies appeared to be predominantly of the immunoglobulin G (IgG) isotype and to be associated with HLA shared epitope alleles (odds ratio = 2.11).

Conclusions

Fibronectin in the inflamed synovia of RA patients can be citrullinated at least at five positions. Together with the flanking amino acids, three of these citrullinated residues comprise two epitopes recognized by RA autoantibodies. Anti-citrullinated fibronectin peptide antibodies are associated with HLA shared epitope alleles.     

Response of microcosm zooplankton to acidification

Zooplankton community transformation in response to soft water acidification was studied in two experimental series using the microcosm method. The dynamics of total abundance, changes in the proportions of the main zooplankton groups, stability of the dominant complex, and species diversity were evaluated. Zooplankton population proved to decrease at all studied low pH (5–6, 4–5, and 3–4) within the first two weeks relative to the control. At water pH 5–6, either Rotifera-Copepoda or Cladocera-Copepoda zooplankton complex was established depending on the initial community composition; while at pH 4–5, Copepoda predominated in the established zooplankton community. The community edificator species was replaced at pH 4–5. The lowest diversity index was also observed at this pH (1.0–1.5 bit/ind.). In addition, the proportion and absolute population of copepod nauplii and cladoceran Scapholeberis mucronata increased at low pH. A decrease in water pH to 3–4 proved to be disruptive for the zooplankton community.Translated from Izvestiya Akademii Nauk, Seriya Biologicheskaya, No. 1, 2005, pp. 100–108.Original Russian Text Copyright © 2005 by Kurbatova.     

Cytokine profile in mice with enhanced or depressed immune response to sheep erythrocytes induced by immunomodulator of bacterial origin--purified staphylococcal toxoid

Influence of immunomodulator of bacterial origin - purified staphylococcal toxoid (PST) - on the synthesisof proinlammatory (IL-1beta, IL-6, TNFalpha, IFN-gamma) and anti-inflammatory (IL- 10) cytokines, as well as cytokines directing the immune response to Th1 (IL-12) or Th2 (IL-4) type was studied in mice. Serum cytokines levels as well as levels of cytokines produced by splenocytes spontaneously or after stimulation by phytohemagglutinin were measured 4 and 24 hours after inoculation of PST. It was shown that PST in wide spectrum of doses (15; 1.5; 0.15 BU per mouse) was able to enhance or suppress synthesis of cytokines. Effect was nonlinear and its direction was depended from cytokine, time interval passed before obtaining the sample and dose of PST. For example, 15 BU of PST enhanced whereas 0.15 BU of PST suppressed the IL-6 production 4 hours after inoculation. Decrease of IL-6 level in serum 24 hours after inoculation of PST was detected. Synthesis of several serum interleukins (IL-2, IL-10) did not changed 4 and 24 hours after inoculation irrespective from dose of PST. It was demonstrated that modulation of humoral immune response in vivo induced by PST did not associated with modulation of cytokine profile. For example, increase of number of cells secreting antibodies to sheep erythrocytes was registered both during increased synthesis of cytokines (4 hours, IL-1beta, IL-6, IL-12) and during period of its depression (IL-6, TNF-alpha, IFN-gamma), as well as during stable production of cytokines (IL-1beta, IL-6, IFN-gamma).