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Biomedical subjects

P Bierling

Publications and source records attributed to P Bierling.

At least 73 records · Page 4Linked to original sources
PubMed1992

Presence of cross-reactive antibody between human immunodeficiency virus (HIV) and platelet glycoproteins in HIV-related immune thrombocytopenic purpura.

We previously reported the presence in platelet eluates of autoantibodies directed against epitopes of the platelet glycoprotein (GP)IIb/IIIa complex in acquired immunodeficiency syndrome (AIDS)-free human immunodeficiency virus (HIV)-infected patients with immunologic thrombocytopenic purpura (ITP). We investigated whether HIV antibodies recognized platelet membrane antigens to determine whether the virus might be directly or indirectly responsible for the thrombocytopenia in this context. Direct eluates of platelets from 25 patients with HIV-related ITP contained IgG reacting with HIV-GP160/120 and also, in 45% of patients, detectable antiplatelet antibodies, immunochemically characterized as anti-GPIIb and/or anti-GPIIIa in 5 patients. Furthermore, serum HIV-GP160/120 antibodies could be absorbed on and eluted from platelets from normal non-HIV-infected healthy blood donors (indirect eluates). In contrast, GP160/120 antibodies present in the serum of nonthrombocytopenic HIV-infected patients were not absorbable on normal platelets in most patients, suggesting a pathogenic role in HIV-related ITP. We performed detailed studies of a patient with the highest titer of both HIV-GP160/120 and GPIIb/IIIa antibodies in direct and indirect platelet eluates. No antibody binding to GPIIb/IIIa-deficient Glanzmann thrombasthenic platelets was detected. Furthermore, binding/elution experiments conducted with insoluble recombinant GP160 (expressed in baculovirus) and purified platelet GPIIb/IIIa demonstrated that the patient's IgG bound specifically, through the F(ab')2 portion, to a common epitope of HIV-GP160/120 and platelet GPIIb/IIIa. This common epitope was present on a recombinant GP160 expressed in baculovirus but absent from another recombinant GP160 expressed in vaccinia virus, suggesting that the cross-reactivity is dependent on the glycosylation or conformational structure of the GP. We conclude that molecular mimicry between HIV-GP160/120 and platelet GPIIb/IIIa may explain at least some cases of ITP in AIDS-free HIV-infected patients.

Autoantibodies↗
PubMed1992

Frequency of the polymorphonuclear neutrophil Fc gamma receptor III deficiency in the French population and its involvement in the development of neonatal alloimmune neutropenia.

We report the case of a healthy woman (K.M.) who, after multiple pregnancies, developed an antibody directed against a nonpolymorphic region of the polymorphonuclear neutrophil (PMN) Fc gamma receptor III (FcRIII-CD16), which caused transient neonatal alloimmune neutropenia (NAIN). The antigenic target of the antibody was determined by an immunoprecipitation procedure and by phenotyping the mother's PMN. These latter did not react with monoclonal CD16 or polyclonal and monoclonal NA1 and NA2 antibodies, demonstrating the absence of PMN-FcRIII and, consequently, the NA-null phenotype. We also determined the frequency of the NA-null phenotype in a healthy, white population. Among 3,377 random blood donors, only four (in addition to K.M.) were PMN-FcRIII-deficient. These five individuals were healthy and only one (K.M.) presented an allo-CD16 antibody. The gene frequency of the NA-null phenotype was calculated as 0.0274 +/- 0.0059. We conclude that PMN-FcRIII deficiency is a rare phenomenon that can lead to CD16 alloimmunization and thus cause NAIN.

Antigens, CD↗
PubMed1992

Platelet alloimmunization after multiple transfusions: a prospective study of 50 patients.

Fifty polytransfused patients were prospectively studied to determine the frequency of post-transfusion alloimmunization and its influence on the response to platelet transfusion. Platelet- and HLA-specific antibodies were detected by means of the standard and antiglobulin-augmented lymphocytotoxicity techniques (LCT), the platelet suspension indirect immunofluorescence test (PSIIFT), and monoclonal antibody immobilization of platelet antigens (MAIPA). HLA antibodies were detected in 13 patients (26%) (IgM = 6; IgG = 6; IgM + IgG = 1). The standard LCT was positive in 12 of these 13 patients. Complement-independent HLA antibodies, only detectable in the PSIIFT and the antiglobulin-augmented LCT, were documented in two patients and were associated with poor post-transfusion platelet recovery in the patient who could be evaluated. All the HLA antibodies were detected in the PSIIFT, while only four were detected in the MAIPA. Platelet-specific alloantibodies were found in two patients by means of PSIIFT or MAIPA and may have led to poor post-transfusion platelet recovery in one patient. Platelet autoantibodies were detected in two patients but were not associated with platelet refractoriness. Paraformaldehyde-dependent platelet antibodies were detected in 11 patients but were not associated with platelet refractoriness.

Adolescent↗
PubMed1991

Infection of megakaryocytes by human immunodeficiency virus in seropositive patients with immune thrombocytopenic purpura.

Twenty-one human immunodeficiency virus (HIV)-positive patients, including 11 acquired immunodeficiency syndrome (AIDS)-free patients with immune thrombocytopenic purpura (ITP), were studied to determine whether the megakaryocytic/platelet lineage was infected by HIV. Because purification of platelets did not reach a level sufficient for unequivocal results by the polymerase chain reaction, in situ hybridization was thus performed. Purified marrow megakaryocytes (MK) from 10 HIV-infected ITP patients were studied using a 35S HIV riboprobe, antisense of an HIV ENV sequence. HIV transcripts were clearly detected in MK from five of these 10 patients, although heterogeneity among MK was observed. In three of these five cases, small amounts of HIV glycoproteins were detected in MK by means of immunofluorescence. In addition anti-HIV antibodies could be eluted from platelets of all patients. In contrast, HIV transcripts were not detected in MK derived from colony-forming units-MK (CFU-MK) cultured in suspension, suggesting either that MK are infected by HIV during terminal differentiation or that HIV-infected CFU-MK are unable to differentiate in vitro. In conclusion, this study suggests that HIV infection of MK may be implicated in the pathogenesis of thrombocytopenia of HIV-positive patients.

Blood Platelets↗
PubMed1991

Brb, a platelet alloantigen involved in neonatal alloimmune thrombocytopenia.

Serum from a pregnant woman with the May-Hegglin anomaly contained a platelet-specific antibody. The serum reacted in the platelet indirect immunofluorescence test (PIIFT) with 97.6% of random donor platelets and those of the father but not with the mother's own platelets. This antibody induced a moderate thrombocytopenia in the infant that responded to infusion of intravenous immunoglobulin concentrates. The platelet phenotypes were PLA1+, Baka+, Bra+/Brb- for the mother, PLA1+, Baka+, Bra-/Brb+ for the father, and PLA1+, Bra+/Brb+ for the neonate. Analysis of the maternal serum with an immunoassay based on monoclonal antibody immobilization of platelet antigens (MAIPA) and immunoprecipitation techniques demonstrated the absence of antibodies directed against HLA class I antigens and that the antigen recognized was located on the platelet-GpIa/IIa complex. This antigen was present on 113/115 random donor platelets, in 7 of the 7 unrelated May-Hegglin platelets, and only absent in 3/24 Bra+ individuals, including the mother. No platelet-specific antibody was present in the serum of the 7 unrelated May-Hegglin subjects. The antigen recognized by this platelet-specific antibody thus meets the criteria defining the antithetic allele of Bra, i.e. the Brb alloantigen.

Adult↗
PubMed1990

[Post-transfusion purpura. An unknown cause of acute immune thrombocytopenia. 4 new cases].

Post-transfusion purpura is characterized by the occurrence of acute immune thrombocytopenia 5 to 10 days after transfusion of platelet-containing blood products in subjects who had been alloimmunized to specific platelet antigens. Four cases are reported here. Three of these 4 patients, who had a rare PLA1 platelet phenotype, had developed, during a previous sensitization (pregnancy n = 2, transfusion n = 1), an allo antibody directed against PLA1 antigen. The fourth patient presented a specific anti-PLA2 antibody. Thrombocytopenia (platelet count between 4 and 40 x 10(9)/1) appeared 1 to 12 days after the responsible transfusion and showed as haematomas (n = 3) or haemoptysis (n = 1). One patient was asymptomatic and remained untreated. The remaining 3 patients received corticosteroids orally associated, in one case, with infusions of human immunoglobulin concentrates. Thrombocytopenia was corrected within 5 to 13 days. In such cases, whenever another blood transfusion is necessary, a preventive treatment with perfectly platelet-free blood products is mandatory. Platelet depletion by freezing-thawing of red cell concentrates is probably not always sufficient, since recurrence was observed with such a product in one of our patients. The exact cause of immune destruction of autologous platelet remains a mystery.

Adult↗
PubMed1990

Pregnancy in women with immune thrombocytopenic purpura.

Thirty-six women with immune thrombocytopenic purpura were studied during 37 pregnancies, and maternal characteristics with predictive value for the fetal platelet count were determined. Nine neonates were thrombocytopenic, with a platelet count of less than 50 x 10(9)/L in eight. Four of these nine neonates delivered to a subgroup of 31 mothers were studied prospectively; the frequency of thrombocytopenia in neonates of women with immune thrombocytopenic purpura was thus 13%. Only two of these nine neonates presented with hemorrhagic syndromes (two, petechial purpura; one, intracranial bleeding). The frequency of neonatal thrombocytopenia was higher in mothers with deep thrombocytopenia and in those who had not responded to corticosteroid treatment following diagnosis. No prognostic value could be assigned to the other maternal characteristics studied, such as a history of splenectomy, maternal treatment at the time of delivery, or the presence of platelet autoantibodies evaluated either with the platelet immunofluorescence test or the platelet Western blot immunoassay.

Autoantibodies↗
PubMed1989

Zidovudine for thrombocytopenic purpura related to human immunodeficiency virus (HIV) infection.

STUDY OBJECTIVE: To determine whether zidovudine is effective in increasing the platelet count in patients with thrombocytopenic purpura related to human immunodeficiency virus (HIV) infection. DESIGN: Nonrandomized controlled trial with two consecutive regimens. SETTING: Immunopathology and hematology clinics at two general hospitals. PATIENTS: Consecutive sample of 34 patients infected with HIV who had thrombocytopenic purpura (platelets less than 50 x 10(9)/L) without visceral bleeding. Twenty-nine patients completed the study; one patient was removed because of drug toxicity. INTERVENTIONS: Zidovudine for 12 weeks, 250 mg every 6 hours orally in 10 patients; and 500 mg every 8 hours orally in 24 patients. MEASUREMENTS AND MAIN RESULTS: Three of ten patients receiving 250 mg every 6 hours and 12 of 24 patients receiving 500 mg every 8 hours had a persistent increase in their platelet counts. In both groups the mean value of the platelet count increased significantly by week 12; from 28 x 10(9)/L +/- 12 (SD) to 57 x 10(9)/L +/- 36 in the first group and from 20 x 10(9)/L +/- 13 to 77 x 10(9)/L +/- 42 in the second group (P less than 0.05 and P less than 0.01, respectively). CONCLUSIONS: Zidovudine is effective on platelet counts in some patients with HIV-related thrombocytopenia. These results suggest that HIV itself may play a direct or indirect role in the pathogenesis of this disorder.

Adult↗
PubMed1989

Immunochemical analysis of platelet autoantibodies in HIV-related thrombocytopenic purpura: a study of 68 patients.

Serum antiplatelet IgG and platelet-associated IgG (PAIgG) were studied in 68 AIDS-free human immunodeficiency virus (HIV)-infected patients with severe immunologic thrombocytopenic purpura (ITP), for the presence of platelet autoantibodies. Serum IgG with antiplatelet activity was found in 72% of the sera. However, the presence of autoantibodies against platelet surface glycoproteins was not found in these sera by means of Western blot and immunoprecipitation procedures. Nevertheless, an immunoblot immunoassay and an indirect immunofluorescence test against semi-permeabilized platelets demonstrated the presence of antibodies in the patient sera, that reacted with intracytoplasmic platelet components, and which might participate in the elimination of platelet fragments. Direct immunofluorescence tests demonstrated an increased amount of PAIgG in 75% of the patients; the bound antibodies could be eluted with ether in 44% of the cases. These eluates were found to bind to normal platelets but not to Glanzmann type I platelets. Finally, immunoprecipitation procedures demonstrated the presence of platelet autoantibodies in six of the 35 eluates studied. These antibodies recognized GPIIb in two cases, GPIIIa in one case, and an unidentified platelet protein of 150 kDa in the three other cases. The discrepancy between sera and platelet eluates was interpreted as being due to the low titre of the antibodies and to their dilution in polyclonal hypergammaglobulinaemia. The present study provides direct evidence that isolated ITP in some HIV-positive patients is due to the presence of platelet autoantibodies. These results, however, do not exclude either direct or indirect involvement of HIV in the platelet destruction.

Autoantibodies↗