bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Immunoglobulin VH Gene, VH4–21, Specifically Encodes Autoanti‐Red Cell Antibodies against the I or i Antigens
Authors: Smith Graham , Spellerberg Myfanwy , Boulton Frank , Roelcke Dieter , Stevenson Freda 
Published: March 2009

AbstractMost autoanti‐red cell antibodies found in patients with cold agglutinin disease are specific for the I or i carbohydrate antigenic determinants. However, antibodies specific for other antigens such as Pr or Sa can also be found, and these are identified by their pattern of reactivity with enzyme‐treated red cells. Recently, it has been shown that the vast majority of anti‐Ii antibodies react with a monoclonal anti‐idiotypic antibody (9G4); this reactivity arises from restriction of the immunoglobulin heavy chains used to encode the antibodies to a single VH4–21 gene, VH4–21. The 9G4 antibody appears specific for this gene product, and we have used it to analyse VH4–21 gene involvement in encoding a spectrum of red cell antibodies of various specificities. The results support the strong association between usage of this gene and anti‐Ii specificity and indicate that it is not generally used by other specificities. In particular, it is striking that the unsubstituted type 2 oligosaccharide antigens (I and i) induce a highly restricted autoantibody response very different from that induced by the sialylated type 2 antigens (Sia‐b,‐1 and lb). The 9G4 antibody therefore provides a simple tool for discrimination between these autoanti‐red cell antibodies, which should be of use in red cell serology.
Mild Course of Fetal Rh D Haemolytic Disease due to Maternal Alloimmunisation to Paternal HLA Class I and II Antigens
Authors: Eichler H. , Zieger W. , Neppert J. , Kerowgan M. , Melchert F. , Goldmann S.F. 
Published: March 2009

AbstractThe patient is a pregnant women of African origin with a prior history of spontaneous abortion and newborn dystrophy. The investigation showed an anti‐Rh D antibody (IgG isotypes 1 and 3) with an indirect antiglobulin tube test (IAT) titre of 1:512. The monocyte monolayer assay (MMA) proved clearly the interaction of Fc receptors with the maternal anti‐D, and so a clinical significance was expected. In spite of this, no signs of severe haemolysis in the Rh‐D‐positive and direct antiglobulin test‐positive fetus could be observed. Furthermore, two HLA class I and II alloantibodies (anti‐A10, anti‐DR13) directed against paternal and fetal antigens were detected in the serum of the gravida. Both antibodies showed an inhibitory effect on the in vitro phagocytosis capacity of mononuclear cells expressing at least one of the corresponding HLA antigens (immunophagocytosis inhibition (IPI) test). Thus, the mild course of haemolytic disease may be explained by an effective inhibition of the fetal mononuclear phagocyte system by maternal HLA class I and/or class II antibodies resulting in a diminished destruction of anti‐D‐coated fetal red blood cells.
Fragmentation of Therapeutic Human Immunoglobulin Preparations
Authors: Page M. , Ling C. , Dilger P. , Bentley M. , Forsey T. , Longstaff C. , Thorpe R. 
Published: March 2009

AbstractSome commercial batches of human therapeutic immunoglobulins (Ig) have been found to show evidence of molecular fragmentation when examined by molecular sizing methodologies including sodium dodecyl sulphate polyacrylamide gel electrophoresis [SDS‐PAGE] and size exclusion high performance liquid chromatography (SE‐HPLC). These batches all demonstrated impaired immunobiological activity (efficacy) as assessed by Fc function measured using a rubella haemolytic assay and as such are likely to be subpotent for therapeutic use. Fragmented Igs were characterized by the presence of at least three protein bands and peaks additional to monomeric IgG. Incubation of Igs with blood enzymes (plasmin and kallikrein) reproduced the fragmentation patterns observed for intrinsically degraded batches, suggesting that fragmentation occurred by contamination with these proteases from the source material (human blood) during manufacture. Intravenous Igs (IVIG) were found to be more susceptible to proteolysis than intramuscular Igs, probably as a consequence of the post‐fractionation processing that some IVIGs receive which may induce molecular alterations, allowing enzyme access and fragmentation. Two of the products examined were found to be relatively resistant to proteolysis and both were formulated by processes that limit enzyme activity. These processes were inclusion of an enzyme inhibitor, α2‐macroglobulin, and formulation at acidic pH. Enzyme carry‐over into the final product is a likely cause of Ig fragmentation, and reduction in levels of such contamination should lead to improvements in product stability and efficacy.
A Comparative Study of Platelets Stored in Polyvinyl Chloride Containers Plasticised with Butyryl Trihexyl Citrate or Triethylhexyl Trimellitate
Authors: Turner V. S. , Mitchell S. G. , Kang S. K. , Hawker R.J. 
Published: March 2009

AbstractPlatelet concentrates (PCs), stored for 5 days in PL 2209, a new polyvinyl chloride (PVC) storage container plasticised with butyryl trihexyl citrate, were compared with those stored in PL 1240, a PVC platelet container plasticised with triethylhexyl trimellitate. In part 1 of the study, pooled platelet‐rich plasma (PRP) was aliquoted into each type of pack and pH, pCO2, pO2, hypotonic shock response, aggregation responses, lactate, glucose and ATP concentrations, and lactate dehydrogenase and β‐thromboglobulin release were compared at days 1, 3 and 5. In part 2, 12 volunteers gave a unit of blood on two separate occasions and PCs produced by the PRP method were stored in PL 2209 or PL 1240 for 5 days before autologous reinfusion of a 111In‐labelled sample. In vitro results demonstrated that PL 2209 was more gas permeable than PL 1240. In part 2 of the study, at day 5, pCO2 was 3.13±0.62 versus 5.14±0.69 (p<0.001), whilst pO2 was not significantly different for PL 2209 versus PL 1240, respectively. pH was better maintained in PL 2209 than in PL 1240 (7.38±0.13 vs. 7.24±0.10, respectively, p<0.01) after storage for 5 days. These results were confirmed by those from part 1. In vivo data were similar for PC stored in the two plastics with a multiple‐hit recovey of 40.9±12.1% for PL 2209 and 37.4±11.3% for PL 1240, and a multiple‐hit survival of 4.89±1.20 days and 5.28±2.06 days for PL 2209 and PL 1240, respectively. γ‐Camera imaging of volunteers showed similar biodistribution of radiolabeled platelets stored in each container. These results demonstrate that PL 2209 is a suitable container for storage of PCs for 5 days.
A Comparative Evaluation of the Sensitivity of Seven Anti‐Hepatitis C Virus Screening Tests
Authors: Couroucé Anne‐Marie , Barin Francis , Botté Christine , Lunel Françoise , Maisonneuve Pascale , Maniez Michèle , Trepo Christian 
Published: March 2009

AbstractThe sensitivity of the most recent generation of anti‐hepatitis C virus (anti‐HCV) screening tests from seven manufacturers was evaluated with a common panel of 530 specimens from 320 HCV‐infected subjects. This panel included 221 samples from 57 seroconverters (53 pre‐sero conversion negative specimens and 168 positive samples) and 309 selected specimens from 263 other HCV‐infected patients of which 19% exhibited NS3 or core reactivity alone with the presence of HCV‐RNA assessed by PCR. None of the seven screening tests detected all infectious and antibody‐positive specimens. However, important differences were observed between these assays in the number of false‐negative results, which seemed mainly due to nonreactivity of antibody to the NS3 antigen.
Impact of Allergy Screening for Blood Donors: Relationship to Nonhemolytic Transfusion Reactions
Authors: Wilhelm D. , Klüter H. , Klouche M. , Kirchner H. 
Published: March 2009

AbstractThere has been some discussion whether the atopic disposition of a blood donor is associated with a potentially higher incidence of hypersensitivity nonhemolytic transfusion reactions (NHTRs). Serum samples from patients who had suffered from NHTRs and samples from the platelet concentrates (PCs) responsible for the reactions were examined for total and specific IgE as diagnostic markers for allergic events. In addition, the allergy prevalence among 1,088 blood donors was determined to analyze the allergy prevalence among our blood donors. Our results indicate that in 90% of cases, allergic NHTRs were associated with specific IgE antibodies in the recipient's serum, indicating the allergic disposition of the patient. In contrast, specific IgE antibodies were detected in only 22% in the transfused PCs. However, among all investigated NHTRs, there was not a single case in which specific IgE antibodies were detected exclusively in the PC. The allergy prevalence among our blood donors was about 26%. In our opinion, the few cases in which the allergic disposition of blood donors in combination with the allergic disposition of the recipients was associated with NHTRs reflects the allergy prevalence among our blood donors in general (26%). On the basis of these findings, we conclude that allergy diagnosis for blood donors is only of minor value in the prevention and prediction of NHTRs, whereas allergy diagnosis for patients who require multiple PC transfusion might be helpful.
Alloimmunization against ly, a Low‐Frequency Antigen on Platelet Glycoprotein Ib/IX as a Cause of Severe Neonatal Alloimmune Thrombocytopenic Purpura
Authors: Kiefel V. , Vicariot M. , Giovangrandi Y. , Kroll H. , Böhringer M. , Greinacher A. , Breitfeld C. , Santoso S. , Mueller‐Eckhardt C. 
Published: March 2009

AbstractNeonatal alloimmune thrombocytopenia (NAIT) is usually induced by platelet‐specific antibodies against HPA‐la (Zwa) or HPA‐5b (Bra). Recently, low‐frequency alloantigens on the platelet glycoprotein (GP) IIb/IIIa complex have been discovered as a cause for NAIT. In this report, a new low‐frequency platelet‐specific alloantigen, ly, is described which induced severe NAIT. The corresponding antigen was detected in 1/249 unrelated German blood donors. Antibody binding assays with trypsin‐digested platelets (ELISA, immunoprecipitation with biotin‐labelled platelets) indicate that the antigen is not localized on the glycocalicin moiety of GP Ibα, but may be situated on the remnant moiety of GP Ibα, GP IX or GPIbβ. Apparently, ly is not related to the HPA‐2 (Ko) antigen system.
Prediction of the Severity of Haemolytic Disease of the Newborn: Quantitative IgG Anti‐D Subclass Determinations Explain the Correlation with Functional Assay Results
Authors: Garner S.F. , Gorick B.D. , Lai W.Y.Y. , Brown D. , Taverner J. , Hughes‐Jones N.C. , Contreras M. , Lubenko A. 
Published: March 2009

AbstractSera containing anti‐D, taken from 44 RhD‐negative women with RhD‐positive infants, were tested in antibody‐dependent cellular cytotoxicity (ADCC) and monocyte monolayer assays (MMA) which used similar target and effector cell populations. In addition, the anti‐D concentration was measured in the Auto Analyzer and the number of IgG1 and IgG3 anti‐D molecules bound to the target red cells was measured by flow cytometry. The results of the functional assays and AutoAnalyzer quantitation were examined for correlation with IgG subclass quantitation and all results were compared for their ability to predict the severity of haemolytic disease of the newborn (HDN). ADCC correctly predicted HDN in 39/44 (88.6%) cases, AutoAnalyzer quantitation in 35/44 (79.5%) and the MMA in 32/44 (72.7%). For all three assays, the number of correct predictions was highest when the maternal serum contained both IgG1 and IgG3 anti‐D. ADCC activity and HDN were correlated with the number of cell‐bound IgG1 molecules (r≥0.58), but MMA activity was most closely correlated with the number of cell‐bound IgG3 molecules (r = 0.68). Hence the superior predictive value of ADCC is due to its ability to reflect the IgG1 component of maternal anti‐D, which has a better correlation than IgG3 anti‐D with the severity of HDN.
A ‘New’ Low‐Incidence Red Cell Antigen, WARR: Unique to Native Americans?
Authors: Coghlan Gail , Crow Martha , Spruell Peggy , Moulds Marilyn , Zelinski Teresa 
Published: March 2009

AbstractInvestigation of a mild case of hemolytic disease of the newborn has led to recognition of a ‘new’ low‐incidence red cell antigen, WARR (ISBT No. 700.55). Data gleaned from two kindreds, both with Native American heritage, exclude WARR from the MNS, Lutheran, Lewis, Duffy, Kidd, Xg, Chido/Rodgers, Kx and Gerbich blood group systems. Serologic or genetic evidence suggests it is not part of the Kell or Yt systems.
Haemolytic Disease of the Newborn due to Anti‐M
Authors: Duguid J.K.M. , Bromilow I.M. , Entwistle G.D. , Wilkinson R. 
Published: March 2009

AbstractA patient with haemolytic disease of the newborn (HDN) due to anti‐M which required exchange transfusion is described. Anti‐M antibodies are usually assumed to be naturally occurring and to consist of immunoglobin M (IgM); many however have an immunoglobin G (IgG) component. In view of this and the described occurrence of HDN, recommendations are made regarding the management of a pregnancy in which anti‐M antibodies are detected.
Studies in Red Blood Cell Preservation 10. 51Cr Recovery of Red Cells after Liquid Storage in a Glycerol‐Containing Additive Solution
Authors: Greenwalt T.J. , Dumaswala U.J. , Rugg N. 
Published: March 2009

AbstractThe purpose of the present study was to compare the 24‐hour recovery of red blood cells stored for 9 weeks in a hypoosmolar additive solution containing 150 mM glycerol to cells stored in Adsol®. Seven units of packed red cells were split into 2 aliquots. To one sample, 100 ml of the experimental additive solution (EAS 25) was added, and to the other, 50 ml of Adsol. At the end of the storage period the cells were labeled with 51Cr. A double chromium technique was used to make it possible to perform comparative autologous studies in the same donor. The 24‐hour 51Cr recovery value for EAS 25 was 73.03 ± (SD) 4.2% and for Adsol 60.9 ± 7.1. At 9 weeks the adenosine triphosphate levels were not significantly better compared to Adsol but the other in vitro measurements were better. New approaches to the study of red cell preservation are suggested.
Evaluation of Storage Conditions of Platelet Concentrates Prepared from Pooled Buffy Coats
Authors: de Wildt‐Eggen J. , Bins M. , van Prooijen H.C. 
Published: March 2009

AbstractFive days storage of pooled platelet concentrates (PCs) with high yields often results in a pH fall and poor platelet morphology despite the use of specific containers. In this study we evaluated two techniques for prolonged storage of PCs with high platelet counts, by measuring pH and platelet swirl. In routine procedures, 90 PCs, prepared from five buffy coats, were stored in a single 1‐litre PL 732 container. After 5 days storage, 51 PCs with platelet counts below 3.1 times 1011/U showed a pH above 6.8 and optimal swirling scores. 29 of 39 PCs (74%) with yields above 3.1 times 1011/U showed pH values below 6.8 and poor swirling scores. These poor results can be prevented by shortening the duration of storage. PCs with high yields can be stored for 5 days either by dividing the concentrate into two containers or by adjusting the platelet count to 3.1 times 1011/U. In the latter procedure, we reduced the volume of the concentrate and found that of 102 PCs, only 9 showed poor values for pH and platelet swirl. The data clearly indicate the importance of measuring the prestorage platelet count to select the optimal procedure for concentrate storage.
The Effect of Cysteine Modification and Proteinases on the Major Antigens (D, C, c, E and e) of the Rh Blood Group System
Authors: Schmitz G. , Sonneborn H.H. , Ernst M. , Blanchard D. , Gielen W. , Dahr W. 
Published: March 2009

AbstractWe have confirmed and extended previous observations showing that the (Rh) D antigen of erythrocyte membranes is destroyed by various reagents that modify cysteine (Cys) residues (Res.) and by trypsin as well as chymotrypsin, using thirty examples of monoclonal or polyclonal anti‐D in heamglutination inhibition assays. We have also shown that most C, c, E, e and BS58 epitopes are inactivated or weakened by most Cys reagents and by these proteinases, using monoclonal and polyclonal antibodies. Inactivation by 5,5‐dithiobis‐(2‐nitrobenzoic acid) was always fully reversible after subsequent dithioerythritol treatment. The essential Cys Res. appear to be buried in the membrane in view of the inability of some reagents to inactivate (iodoacetamide, iodoacetic acid) or reactivate (reduced glutathione) the antigens. Data obtained with N‐ethylmaleimide indicate that inactivation of the C and c antigens is, at least in part, attributable to (a) Cys Res. that is (are) different from that (those) involved in the E and e antigens. Data obtained with the Cys reagents and the proteinases suggest that more than one peptide loop of the Rh proteins is involved in the major Rh antigens.
CD8+ Lymphocyte Decrease in HIV Disease: Association with Anti‐CD4+ but Not with Anti‐CD8+ Lymphocyte Autoantibodies
Authors: Daniel V. , Süsal C. , Weimer R. , Zipperle S. , Kröpelin M. , Zimmermann R. , Huth‐Kühne A. , Gerhard I. , Maier H. , Opelz G. 
Published: March 2009

ABSTRACTHIV+ patients form autoantibodies against CD4+ and CD8+ lymphocytes. It was shown that anti‐CD4+ lymphocyte autoantibodies are associated with the depletion of CD4+ cells. In the present study we analyzed the relationship of anti‐CD4+ and anti‐CDS+ autoantibodies with the CD8+ lymphocyte decrease commonly observed during HIV disease. IgM and IgG antibodies as well as complement fragments were determined on the surface of CD4+ and CD8+ lymphocytes using double fluorescence flow cytometry. Anti‐CD8+ lymphocyte autoantibodies were found more often in HIV+ hemophilia patients (75/105 = 71%) than HIV‐ hemophilia patients (13/37 = 35%; p<0.0001), patients with pharyngeal carcinoma (20/44 = 45%; p = 0.002), habitual abortions (3/13 = 23%; p = 0.0009) or healthy individuals (93/223 = 42%; p< 0.0001). Anti‐CD8+ antibodies, mostly of the IgM type, occurred significantly more frequently than anti‐CD4+ antibodies in healthy controls (p< 0.0001), patients with pharyngeal carcinoma (p = 0.0001), or HIV‐ patients (p = 0.01). In HIV+ patients, however, anti‐CD4+ autoantibodies were found more often than anti‐CD8+ antibodies (85 vs 71%; p = 0.02). 70 of 104 (67%) HIV+ patients had autoantibodies on both CD4+ and CD8+ lymphocytes and the IgG/IgM/C3d autoantibody pattern was identical in 31 (44%) of the patients. Interestingly, peripheral blood CD8+ cell counts were significantly associated with anti‐CD4+ (p = 0.01) but not with anti‐CD8+ lymphocyte autoantibodies. It is hypothesized that the inhibition and depletion of CD4+ cells by anti‐CD4+ autoantibodies is associated with a loss of regulatory functions that leads to a depletion of antiviral cytotoxic CD8+ lymphocytes.
Spectrotype Analysis of Human ABO Antibodies: Evidence for Different Clonal Heterogeneity of IgM, IgG, and IgA Antibody Populations
Authors: Rieben Robert , Frauenfelder Agnes , Nydegger Urs E. 
Published: March 2009

ABSTRACTClonal characteristics of ABO antibodies in 18 paired samples of serum and breast milk were analyzed by isoelectric focusing and affinity immunoblotting. Anti‐A and/or ‐B (anti‐A/B) IgM showed a uniform, polyclonal spectrotype with more than 20 bands and only minimal interindividual differences. In contrast, IgG spectrotypes were oligoclonal (< 12 bands) and individually distinct. IgA of serum as well as of breast milk showed oligoclonal motifs of up to 15 bands, but with more interindividual variance in intensity than IgM. The bands did not appear at an identical pH in milk and serum samples. The uniformity of IgM spectrotypes could be due to an absence of somatic mutations and thus reflect the use of unmutated germline genes. The greater clonal heterogeneity of IgG as compared to IgA indicates a difference in isotype‐switch regulation. Somatic hypermutation may be less active during the switch from IgM to IgA than during the switch to IgG, or the latter switch may be accompanied by a repertoire shift. Alternatively, the anti‐A/B IgA and IgG antibody populations could be derived from different clonal precursors.
The Rh Antigen D: Partial D Antigens and Associated Low Incidence Antigens
Authors: Tippett P. , Lomas‐Francis C. , Wallace M. 
Published: March 2009

AbstractThe expression of the Rh antigen D varies quantitatively and qualitatively (partial D); published information and 15 years' work studying D variants are discussed in this review. D epitopes correspond to the reaction patterns of monoclonal anti‐D with partial D antigens. Partial D antigens can be reported in terms of their D epitopes but the epitope profile of cells with a quantitative variant of D (weak D) is difficult to determine reliably by haemagglutination tests. Nine partial D antigens, categories II‐VII, DFR and two not previously reported, are identified by their epitope profiles and by association with low incidence antigens. Monoclonal anti‐D recognize 16 D epitopes and more epitopes are anticipated. The specificities of polyclonal anti‐D made by people with partial D antigens are considered in terms of possible D epitope specificities: recognized epitope specificities, or combination thereof, were not able to account for all observed reaction patterns of anti‐D made by immunized individuals with partial D pheno‐types. An attempt is made to understand partial D antigens and their associated low incidence antigens in terms of the molecular genetic information available.
HCV‐Infection in Blood Donors: Association between Anti‐HCV Core IgM Antibodies and Serum HCV RNA
Authors: Ounanian‐Paraz A. , Morel‐Baccard C. , Barlet V. , Gueddah N. , Schweizer B. , Bensa J.C. , Zarski J.P. , Seigneurin J.M. 
Published: March 2009

AbstractAmong 47 blood donors tested positive with HCV EIA 2.0 Abbott, 27 (57.4%) also reacted with four ‘third‐generation’ EIAs. The presence of anti‐HCV antibodies was confirmed with 3 different immunoblot assays in 16 of 27 sera (34.0%) while 10 samples (21.3%) had indeterminate profile with antibodies usually directed against structural core antigen. Anti‐HCV core IgM response was found in 12 of 47 sera (25.5%) and HCV viremia detected by the polymerase chain reaction (PCR) procedure was observed in 15 samples (31.9%). A comparative study of the different markers confirmed a good correlation between a strong antibody response in EIAs and immunoblot assays and the presence of HCV RNA in the serum; only 2 immunoblot indeterminate samples were PCR positive. An association was observed between IgM antibodies against ‘core’ epitopes and HCV RNA carriage: all IgM‐positive sera were found positive by PCR. However, the direct detection of viral genome remains the best method for identifiying HCV carriers in the blood donor population.