1/30. Hereditary homozygous heparin cofactor ii deficiency and the risk of developing venous thrombosis.heparin cofactor ii (HCII) is a specific inhibitor of thrombin in the presence of heparin or dermatan sulphate. Although there have been reports on families in which a heterozygous HCII deficiency is associated with thromboembolic events, several epidemiological studies revealed that heterozygous HCII deficiency is as prevalent among healthy subjects as it is among patients with deep venous thrombosis (DVT). It is therefore not yet clear whether HCII is or is not a thrombotic risk factor. We analyze and describe in an extended family the biochemical and genetic thrombophilic risk factors and evaluate the potential thrombotic risk involved in homozygous and heterozygous HCII deficiency, either alone or associated with other thrombotic or circumstantial risk factors. The propositus has had three episodes of DVT and a pulmonary embolism. During the first episode of DVT the patient was diagnosed as having AT deficiency. Later, a functional and antigenic HCII deficiency, compatible with the homozygous form, was detected. The family study shows that both the propositus and her sister have homozygous HCII deficiency and that 12 of the 27 family members have heterozygous HCII deficiency. This is possibly the first case report on a homozygous phenotype for the HCII deficiency with. in addition, partial AT deficiency. The propositus has suffered several thrombotic events, unlike the other 12 family members with heterozygous HCII deficiency and her sister, who is also homozygous for this disorder. We suggest that HCII deficiency may play a limited in vivo role as a thrombotic risk factor unless associated with AT deficiency or another congenital thrombotic risk factor.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/30. Autoimmune neutropenia in pregnant women causing neonatal neutropenia.Autoimmune neutropenia (AIN) can occur during pregnancy. However, neonatal neutropenia occurring in an infant born to a mother with AIN has only rarely been documented. Recently, we have experienced two cases of AIN during pregnancy, both of which caused severe yet transient neonatal neutropenia (< 0.3 x 10(9)/l), probably as a result of transplacental maternal anti-neutrophil autoantibodies. The anti-neutrophil antibodies seemed to be against antigens other than NA1/NA2 because the autoantibodies did not bind to neutrophils of specific NA types selectively in the granulocyte indirect immunofluorescence test. Although AIN is a relatively uncommon disease, neonatal neutropenia caused by maternal AIN may not be quite as rare.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
3/30. A functional platelet fibrinogen receptor with a deletion in the cysteine-rich repeat region of the beta(3) integrin: the Oe(a) alloantigen in neonatal alloimmune thrombocytopenia.This report describes a new low-frequency alloantigen, Oe(a), responsible for a case of neonatal alloimmune thrombocytopenia (NAIT). In a population study none of 600 unrelated blood donors was an Oe(a) carrier. By immunochemical studies the Oe(a) antigen could be assigned to platelet glycoprotein (GP) IIIa. Sequencing of GPIIIa complementary dna from an Oe(a) ( ) individual showed deletion of a lysine residue at position 611 (DeltaLys(611)). Analysis of 20 Oe(a) (-) and 3 Oe(a) ( ) individuals showed that the DeltaLys(611) form of GPIIIa was related to the phenotype. Anti-Oe(a) reacted with the DeltaLys(611), but not with the wild-type isoforms on stable transfectants expressing GPIIIa, indicating that DeltaLys(611) directly induces the expression of Oe(a) epitopes. Under nonreducing conditions the Pro(33)DeltaLys(611) variant migrated with a slightly decreased molecular weight compared to the Pro(33)Lys(611) isoform suggesting that DeltaLys(611) has an influence on the disulfide bonds of GPIIIa. The Pro(33)DeltaLys(611) GPIIIa could undergo conformational changes and bind to fibrinogen in a similar manner as the Pro(33)Lys(611) isoform. No difference was found in the tyrosine phosphorylation of pp125(FAK), suggesting that DeltaLys(611) has no effect on integrin function. In contrast to all other low-frequency antigens, the DeltaLys(611) isoform was associated with the HPA-1b, but not with the high frequency HPA-1a allele. Comparison with GPIIIa dna from nonhuman primates indicated that the HPA-1a allele represents the ancestral form of GPIIIa. It can be assumed that the Oe(a) form did arise as a result of a mutational event from an already mutated GPIIIa allele.- - - - - - - - - - ranking = 7keywords = antigen (Clic here for more details about this article) |
4/30. Protein S gene mutation in a young woman with type III protein s deficiency and venous thrombosis during pregnancy.BACKGROUND: We attempted to identify a gene defect in a young woman with type III protein s deficiency and venous thrombosis during pregnancy. methods: Measurements of total and free PS antigen levels in plasma were carried out using an enzyme-linked immunosorbent assay. Plasma PS cofactor activity was determined by a clotting assay using activated factor v as the substrate. Genomic dna prepared from peripheral blood was amplified by polymerase chain reaction (PCR) with PROS1-specific oligonucleotide primers. PCR products were sequenced on both strands using specific oligonucleotide primers. RESULTS: Plasma PS cofactor activity was undetectable in every measurement at 36 weeks of gestation, as well as at 2 weeks and 4 months after delivery. Plasma total PS antigen levels were 70% and 67% at 2 weeks and 4 months after delivery, respectively. Free PS antigen level was 24% at 4 months after delivery. Of all exons analyzed, codon 295 of GGC in exon 10 was substituted for AGC. This missense mutation predicted an amino acid change of glycine to serine. CONCLUSIONS: Measurements of total and free PS antigen levels along with PS activity indicated that this was a case of type III PS deficiency. dna analysis identified a heterozygous missense mutation of codon 295 in the PS gene, substituting glycine for serine.- - - - - - - - - - ranking = 4keywords = antigen (Clic here for more details about this article) |
5/30. incidence and specificity of HLA antibodies in multitransfused patients with acquired aplastic anemia.BACKGROUND: This study aimed to establish the prevalence and characteristics of anti-HLA in antibody acquired aplastic anemia patients following cessation of antithymocyte globulin therapy and to characterize antibody in terms of epitope specificity. STUDY DESIGN AND methods: One hundred and fifty multitransfused, untransplanted patients from eight European centers were investigated by serologic methods. RESULTS: Sixty-two percent were antibody positive. Eighteen HLA-Class-I-specific antibodies (15 IgG, 3 IgM) were identified in 13 patients; 13 antibodies were specific for HLA-A epitopes and 5 for HLA-B. Epitope analysis identified significant correlation between serum reactivity and amino acid substitutions associated with HLA-Class-I epitopes. An excess of antibodies to HLA-A1-associated cross-reactive groups was identified. There was no significant difference in antibody frequency in patients taking cyclosporine compared to those who were not. CONCLUSION: Data suggested a contribution from B cell memory of alloantigens introduced during pregnancy. In some cases, antibody production continued many years after the last transfusion, and although the target varied between individual patients, the antibody to HLA was focused on a few specific Class I epitopes, the majority of which mapped to the HLA-A molecule.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
6/30. Conformational Asn187Asp/Lys antithrombin variants and thrombosis. Clinical and biological features in 13 new heterozygotes.Antithrombin Rouen VI (N187D) is a rare conformational thermolabile variant. The unique symptomatic carrier reported in the literature developed 3 thrombotic events during pregnancy, in each case in a context of pyrexial infection. In fresh plasma, antithrombin activity and antigen level were normal but in vitro experiments demonstrated the presence of a thermolabile variant, suggesting that fever could be a trigger for thrombosis in N187D carriers. The RouenVI variant was further found in two asymptomatic brothers. In these subjects, it was associated with normal antigen level but reduced activity. In order to better delineate the functional and clinical consequences of the N187 variants, we have studied a series of seven subjects from two distinct families heterozygous for the Rouen VI mutation. Antithrombin levels were normal or borderline in these patients. Thermostability of plasma antithrombin was normal. We have also studied six subjects heterozygous for a new mutation, 6462C>G,which results in an asparagine to lysine substitution at residue 187. In these patients, the N187K mutation is associated with a clear type II deficiency and decreased thermostability of the plasma protein has been demonstrated. That the N187D mutation has milder consequences on plasma antithrombin activity than the N187K mutation is in agreement with structural predictions. About 50% of the N187 carriers studied have suffered venous thrombotic events, strongly suggesting that both mutations are risk factors for thrombosis, but none occurred during pyrexial infections.- - - - - - - - - - ranking = 2keywords = antigen (Clic here for more details about this article) |
7/30. Fetal-neonatal alloimmune thrombocytopenia and unexpected Glanzmann thrombasthenia carrier: report of two cases.BACKGROUND: Discrepancy between phenotyping and genotyping during the investigation of maternofetal alloimmunization leads to the identification of defects on genes encoding membrane glycoproteins (GPs) IIb and IIIa. STUDY DESIGN AND methods: Human platelet (PLT) alloantigen (HPA)-1 and -3 PLT phenotypes and genotypes were performed by use of, respectively, the monoclonal antibody-specific immobilization of PLT antigens and the polymerase chain reaction (PCR)-sequence-specific priming techniques for up to 2400 families with thrombocytopenic newborn. When a discrepancy was detected, genomic dna from the mother was amplified for coding sequences of either the GPIIb or GPIIIa genes. The genetic abnormality responsible for the discrepancy was determined by direct sequencing of the PCR products. RESULTS: Two cases of discrepancy were identified among 2400 families tested. In the first case, Mother L, serologically assigned as HPA-1b-homozygous, was genotyped HPA-1a/1b. In the second case, Mother S, serogically defined HPA-3b-homozygous, was genotyped HPA-3a/3b. dna sequence analysis revealed for Mother L a T(1447)-->C a point mutation within exon 10 of the GPIIIa gene and for Mother S a C(480)-->G point mutation within exon 4 of the GPIIb gene. These mutations reported in Glanzmann thrombasthenia (GT) patients account for nonexpression of the implicated allele on the PLT surface. Thus, the mothers are GT carriers. Alloantibodies, hallmarks of immunization, were not detected in the maternal serum samples. CONCLUSION: Although this situation is rarely encountered, it is important to combine phenotyping and genotyping to avoid false PLT typing assignation and erroneous diagnosis when alloimmunization might occur.- - - - - - - - - - ranking = 2keywords = antigen (Clic here for more details about this article) |
8/30. Twin pregnancy complicated by severe hemolytic disease of the fetus and newborn due to anti-g and anti-C.BACKGROUND: Hemolytic disease of the fetus and newborn caused by anti-G antibodies is rare, and in most previously reported cases, leads to a mild anemia. The RhG antigen is usually found in association with both RhD and RhC. We report a case of a twin pregnancy affected by both anti-G and anti-C alloantibodies leading to severe hemolytic disease of the fetus and newborn requiring multiple intrauterine transfusions and prolonged postnatal therapy. CASE: A patient with a prolonged history of previously affected pregnancies due to anti-D and anti-C was subsequently found to be affected with anti-G instead. She required aggressive therapy during her pregnancy, initially with intravenous immune globulin and plasmapheresis until umbilical blood sampling and intrauterine transfusions were feasible. CONCLUSION: Although hemolytic disease of the fetus and newborn due to anti-G antibodies is rare and usually mild, these pregnancies should be followed up closely and in utero therapy should be offered if necessary.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
9/30. Administration of rituximab during the first trimester of pregnancy without consequences for the newborn.Rituximab, a chimeric mouse/human monoclonal antibody that binds to the CD20 antigen, is part of current treatment of many B-cell malignancies and several autoimmune diseases. Very few cases of rituximab administration during pregnancy have been described. We report here the case of rituximab administration during the first trimester of pregnancy in a woman with autoimmune hemolytic anemia. No significant effects were observed in B-cell counts or the immune status of the newborn.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
10/30. Severe neonatal hemolysis due to a maternal antibody to the low-frequency Rh antigen C(w).C(w) is a low-frequency antigen in the Rh blood group system with a prevalence of approximately 2% in whites. Although anti-C(w) is not an uncommon antibody in pregnancy (0.1% incidence), clinically significant hemolytic disease of the newborn is highly unusual. We report the case of an infant with severe hyperbilirubinemia and persistent anemia due to a high-titer maternal C(w) antibody. The medical literature relating to maternal C(w) alloimmunization and neonatal outcome is also reviewed. In addition, recommendations are made regarding the management of pregnancies and newborns complicated by antibodies to C(w).- - - - - - - - - - ranking = 5keywords = antigen (Clic here for more details about this article) |
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