The antigenic index which takes a window of six neighbouring T-cell receptor manifests specificity for a given antigenic amino acids into consideration, can be calculated along peptide as well as for the allele of MHC molecule to which the allergenic polypeptide. Regions with high antigenic it is bound.
Exogenous antigens such as allergens. This predicted epitope could be are internalized by the APC from the extracellular space confirmed experimentally. However, we identified also B- resulting predominantly in peptide-MHC class II com- cell epitopes within areas of low antigenic indices, e. Baur those currently available gives a high level of correct prediction of B-cell epitopes.
Y The same is true for T-cell epitopes. Although amphi- pathic helices [47] as well as a certain pattern of amino » acid seqtienees glycin followed by two hydrophobic 5I m r l residues [48] were frequently found to behave as T-cell epitopes. Even if both algorithms are combined, there is only partial :l accordance between predicted and evaluated T-cell epi- topes within Chi t 1 component III Fig.
The T-cell response was either investigated in the 0 mouse system or by stimulating peripheral blood lympho- R! For example studies of the Amh D a I allergen of ragweed [54].
In this way. The IV- and the C-tenninal 1 I 1 sequences of Chi i I component III as well as the central z part of the molecule, namely residues containing the heme binding region, were immunodominant [23] Fig. Screening was performed using solid-phase bound tryptically derived as well as overlapping synthetic pep- tides of 20 and eight amino aeid lengths respectively.
According to Jameson and Wolf [45], three B-ceil Hydrophilicity was predicted either to a Fig. Each of these studies showed that Kytc Doolittle or b Hopp and Woods.
Linear B-ccll epitopes recognition sites for T-cells and B-ceils are frequently identified so far are located within the A'- and the C-tcrminal closely related or even identieal in the allergen Chi t I region of Ihe molecule [15].
The iippearancc of these molecules at a distinct developmental stage of lymphocytes suggests that they function as receptors for external signals directing cells to the next phase of response. In the cell surface marker expression between allergic and non-sensitized donors, signiftcant dilTerences could be evaluated in response to Chi i I. In cultures of peripheral blood lymphocytes. It can be assumed that such antigen-specillc changes in the profiles of expressed lymphocyte surface markers may develop into valuable diagnostic indicators of sensitization.
Genetic aspects of IgE-mediated hypersensitivity Human leucocyte antigen genes are extremely diverse; distinct dilTerenl forms of HLA molecules occur in diflerent individuals. This genetic polymorphism results in individual immime response variations and might bean adaptive evolutionary mechanism to ensure immune recognition lor a large variety of immunologic challenges and pathogens. Disease susceptibility that is associated with specific HLA genes can perhaps be viewed as an unintended consequence or bystander ctlect of maintain- ing a polymorphic array of HLA molecules in the population.
More than 70 diseases having to some degree genetic associations with the HLA complex were de- scribed, for example autoimtnune diseases like rheuma- toid arthritis or type I diabetes [57]. T-ccll epitope mapping of Clii I I component when measuring the Chi t I-specilic proliferation of peripheral blood lymphocytes PBL , significant diHerences between patients, exposed and non-exposed controls were found [19,23].
Using overiappiiig pcptides for Ihc. With the exception of sequence lt 2-IO9. Baur Furthermore, molecular genetic studies of human or Phytohaemagglutin-induced T-cell proliferation was immune responsiveness revealed significant associations not influenced in our experiments, unspecific immuno- between particular class H HLA phenotypes und the suppression is not probable [23].
In accordance with our presence of specific serum IgE antibodies lo several highly results, immunomodulation of ihe Dermatophagoides- purified allergens.
Lol p II; DR 3 [ Those determine whether peptides can also be used in riro as associations indicate a very small number of major immunomodulators or whether other strategies inducing epitopes of the antigen to be recognized by just a few class anergy of the respective IgE-mediatingTH-2 cells will be H molecules. Since these In conclusion, the well characterized allergen Chi t I DR- and DQ-genes are in strong linkage disequilibrium, may serve as a good model for future allergy research.
Leyko W. In role of Chironomus haemoglobin. Weber E. Structure of erythrocruorin in antibodies to HLA-DQ showed interindividual different different ligand states refined at 1.
J Mol Biol results [20]. Detection of potent insect antigens for response to Chi t I. Ziegler D. Braunitzer G. Localization of a clinically relevant antigenie determinant within an insect A curative therapy for immediate type allergic diseases is hemoglobin erythrocruorin of chironomus sequence not yet available. In Ed. Ring J. Dewair M. P'ruhmann G ei ul. Hyposensitiza- Chironomids non-biting midges : Localization of the anti- tion is of limited value or even uneffective as shown in genie determinants within certain polypeptide sequences of many controlled studies [ Al present, different hemoglobins erylhrocruorins of Chironomus Ihummi strategies are pursued by immunologists.
Recent progress thummi Diptera. Allergy Clin. In understanding allergy has identified several possible 6 Baur X, Dewair M. Haegele K et at. Common antigenie targets for selective immune intervention: at the major determinants of haemoglobin as basis of immunological histocompatibility complex on antigen presenting cells, at cross-reactivity between chironomid species Diptera.
Chir- the T-cell receptors, at CD4 and CD8 and other accessory onomidae : studies with human and animal sera. Clin Exp molecules. Immunol ; Structure, antigenie We could previously show that downmodulation of determinants of some clinieaily important insect allergens: Chi I I-specific T-cclI proliferation with allergen-derived Chironomd hemoglobins.
Science ; This means that competition of 8 Baur X, Liebers V. Immunological cross- low or non-stimulating peptides with the allergen at the reactivity of hemoglobins in Ihe Diptera family Chironomi- respective HLA-molecules or T-cell receptor sites may dae.
Allergy ; Chironomid midge allergy. Jpn J Allergol ; subsequent reduction of hypersensiiivity. Since Tetanus- Ist die Hyposensibilisieriing noch ein adaquales allergens Chi 11 : Identified and predicted B-cell and T-cell Verfahrcn zur Behandlung des Asthma bronchiale? Pneu- epitopes. Allergy Clin Immunol lii; M. Baur X. Liebers V. Hypersensitivity to hemoglo- It Baur X.
Insect hemoglobins Chi i I of the bins of the diptera family chironomidac: Structural and Diptera genus Chironomus are relevant environmental. Molecular approaches to the study of Environ Health l;l Monographs in Allergy. Basel: Karger, ; 12 Baur X. Mazur G. Steigemann W. B-cell und T- Myamoto T. Shibuya T. Skin test and radioallergo- In: Kraft D. London: CRC Press. Hypcrscnsitivity to larvae of ; Shogaki Y..
V, Liebers V, Czuppon A. Chironomi- OshimaS. Allergy lo insects in Japan. High frequency of IgE dae hemoglobin allergy in Japanese.
Swedish and German antibody response lo jnsecis moth, butierdy. Allergy V, Chen Z. Allergo J. Immunol Chen Z. Raulf M, Baur X. Epitop in Myamoto T. Mite and midge allergy. Mol Immunol. Kay AB. Widespread immunoglobulin E- 17 Liebers V. Chalbaba S. Cladotanytarsus lewisi Oiptcra: Chironomidae. Europ Resp J Diagnosis by radioallergosorbent test.
J Allergy Clin Immu. Baur X, Modrow S. Stimulation of 32 Tee R. Cranston P. Dewair M ct al. Stimulation of Allergy ; Johnson R. Lake fly allergy; hemoglobin allergen Chi Int Arch Appl Immunol Incidence of chironomid sensitivity in an atopic popuhition. Fundamental studies on ehironomid genetic aspects of Chi t I allergy. Immunomodulating allergy. In: Kraft D. Schon A eds. Molecular Biology and immunology of allergens. London: ; CRC Press. Humoral immune schaft fiir Allergic- und lmmunitatsforschung.
Potsdam response to the insect allergen Chi t I in aquarists and fish Studies on the 22 Liebers V, Raulf M. Allergen-induced expression of evolutionary relationships between hemoglobins in Chiro- cell surface markers on lymphocytes of Chi i I-sensitized nomus pallidivittaius and C. Isolation and patients.
Allergy , in press. Raulf M, Mazur G. Modrow S. Epitope globins. J Mol Evol ; Analysis of immunomodulation of the Chi t I immune response. J antigenic determinants shared by two diflercnt allergens Allergy Clin Immunol.
Epitope mapping of major goides pteronyssinus and chironomid midge Chironomus insect allergens ehironomid hemoglobins with monoclonal yoshimatsui. J Allergy Clin Immunol ; Structure-ininiunogeni- 25 Mazur G.
Modrow S, Beekcr WM. A common city relationship of a peptide allergen, melittin. Mol Immunol Chironomid 39 Goodman M. Liebers and X. Baur The analysis of a protein-polymorphism. Fivolulion of mice. Evidence for major and cryptie epitopes. Roberts C. Nunn T, Kuo M. Mapping human T Chem Rozynck P, Wcich B. Fricdl H. Schmidt E. Intron insertion in hemoglobin genes of Chironomus.
New 57 Robinson D, Nepom G. The human major histocompatibi- Trends in Geneties ; abstraet of the annual meeting of lity complex and disease susceptibility. Autoimmune Dis- the genetie society. Personal eommunication. Structural features of allergens large and small with Genetics. Presently, measurement of HbF level in adults is used as diagnostic tool in few cases: a detection of fetal cells in maternal circulation as an important support for the clinical diagnosis of feto-maternal hemorrhage — a potentially life-threatening obstetric complication, b persistence of high level in blood as an assistance in the diagnosis of hemoglobinopathies, especially sickle cell disease and c its increase in blood as assistance in evaluating recovery from hematopoietic cells transplantation Trent, ; Solomonia et al, Physiologically, HbF is of great advantage to normal developing fetus.
This is because at this condition, HbF has low affinity for 2,3-diphosphoglycerate. This low affinity confers on it the higher binding capacity for oxygen, which is of great advantage to the fetus to withstand or resist anoxemia and avoid carbon dioxide toxicity. In adult, high level of HbF in blood has been linked to hemopoietic stress like hemolysis or profuse bleeding, as well as other causes of constant blood loss.
The best described intentional frequent blood loss is through commercial blood donation. In voluntary blood donation, donors are restricted to three to four donations per year.
This is because it takes adult males about 12 weeks and adult female 16 weeks to replace a pint of blood given out. However, commercial blood donors tend to donate as many times as they can access the service per year due to its paltry financial return.
Such donors are usually touts who have little or no other means of livelihood; instead, they rely on the financial returns from the donation to meet most of their financial needs. It is worthy to note that in these distressed economies, governments are not in control of blood transfusion services. Thus, maladministration and rush to gain from the appointment leave such centers non-functional, or at best barely functional that they cannot meet the purpose for which they were established.
Thus, stand-alone laboratories capitalize on this to create small or makeshift blood banks. With this situation, commercial blood donors move from one blood bank to another to donate as frequently as they want without being spotted. After each donation, they are given multivitamin tablets to be taken for some days to enhance erythropoeisis. The multivitamin gesture, which increases erythropoeisis, will encourage the donors to come back or move to another laboratory for another donation earlier than necessary.
The need to track such donors and dissuade them from making frequent donations cannot be overemphasized. However, there is dearth of methods for the identification of these multiple blood donors, except those that can be physically identified.
It is possible that frequent blood donation can induce hemopoietic stress in such donors, prompting increase in the concentration of HbF in the donor. If this is true, then the level of HbF in blood donors, who have no other possible cause of the increase, can be used as an indicator of how frequent or long the individual has donated blood. Materials and Methods Ethical clearance: This is a cross-sectional study done between January and June, Subjects: A total of subjects aged between 20 and 50years were recruited for the study.
This comprised of 88 donors and 64 controls. These control subjects were age-matched apparently healthy students and workers of the teaching hospital who have never donated blood or have not done so in six months prior to the study. Sample collection: A total of 3. The packed cells were then subsequently lysed using equal volumes of water and carbon tetrachloride.
The lysed cells were vigorously shaken for a minute and then centrifuged at rpm for 30 minutes. The clear supernatant was then transferred to a clean test tube for use. Samples were collected and processed in batches of 5 to 10 for easy handling. Statistical analysis: Graph Pad Prism 5. Results The results from this study showed that commercial blood donors have mean hemoglobin F level of 0.
Figure 1 is a comparative study of the mean percentage hemoglobin F in commercial donors and non-donors controls according to age. The results from commercial blood donors at different age group were 0. Figure 1 1. The results were 0. This implies that the older the donor the more percentage of the hemoglobin.
Figure 3 0. On formation, the hemoglobin found in fetuses is termed embryonic hemoglobin which usually switches over to fetal hemoglobin within the first few weeks of life, approximately 10 to 12 weeks of life. This may account for observed increase in percentage HbF in adult females during pregnancy Italia et al, ; Dana and Fibach, As this scenario occurs under physiological condition, there is continuous decline in concentration or level of the preceding form of hemoglobin such that at adult life, fetal hemoglobin level becomes negligible about 0.
An exception is in hereditary persistence of fetal hemoglobin seen in certain genetic abnormalities. Therefore, any time significant level of HbF is found in apparently healthy non-pregnant adult, it should be attributed to erythropoietic stress.
Thus, the finding of significantly increased HbF levels in this study among apparently healthy blood donors is an indication of increased erythropoietic stress from frequent blood donation.
By extension, the same gene may account for the ability of the commercial donors to recover easily and fairly well, affording them the opportunity to donate several times per year with little or no observable health shortcoming.
It may also be related to increase in erythropoietin levels, leading to bone marrow expansion as seen in beta thalassemia syndromes Rees et al, By this mechanism, those with more donations will have higher HbF levels, making HbF level an indicator of how frequent or long one has donated blood.
The results of this study also showed that HbF levels in commercial donors increased significantly as the age of the donors increased, showing strong positive correlation between age and HbF level under erythropoietic stress.
This finding is in disagreement with known physiological norm which posit that HbF level decreases as age increases Rochette et al, Moreover, the results from the controls showed that HbF levels decreased as age increased. Though the correlation in controls was not statistically significant, it is a confirmation that significant correlation obtained from commercial donors was as a result of erythropoietic stress, implying that the older donors have donated blood more than the younger ones.
Occasional or well spaced blood donation has been postulated to have some advantages including reduced risk of obesity, cancer, hemochromatosis, liver and pancreas damages and improved cardiovascular and general health BMRS, However, frequent and long term blood donations without giving enough time for cell recovery will likely have damaging effects. Long term adverse effects of frequent blood donation like refractoriness of the bone marrow cells, which leads to anemia and anemic heart failure, may be the same features seen in some cancer cases where increased HbF levels were also observed Rautonen and Siimes, ; Wolk et al, ; Wolk et al, ; Wolk and Martin, Moreover, short term adverse effects like bruising, continuous bleeding, dizziness, lightheadedness and nausea, pain and physical weakness are constant experience, some of which are experienced even with first time donors.
Pathetically, the paltry financial returns realizable from this practice make these commercial blood donors to overlook and hide these obvious adverse effects, as well as lazy and unable to struggle for other means of livelihood.
Therefore, insisting on good spacing between one donation and another will not only ensure the derivable health advantages but will also help to avoid these adverse effects and encourage the donors to seek other means of providing for themselves.
In addition, the practice will give ample time for the erythropoietic cells to recover fully from each stress, affording the donor the opportunity of giving rich blood unit each time. Conclusion The results of this study showed that HbF level increased significantly as number of blood donation increased.
Considering the benefits of presence or increased level of HbF in individuals, the results seem to encourage unlimited number of blood donation per donor per year. However, one cannot forget easily the consequences of such action, which outweighs the advantages. Governments are advised to take full control of Blood Transfusion Centers, appoint qualified personnel to manage them and find a way of identifying donors to avoid multiple donations.
References 1. Fetal hemoglobin in sickle cell anemia. Blood 1 : DOI: Health Benefits of Donating Blood. Dana M, Fibach E Fetal hemoglobin in the maternal circulation - contribution of fetal red blood cells. Hemoglobin 42 2 :
0コメント