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Biomedical subjects

Philippe Bierling

Publications and source records attributed to Philippe Bierling.

12 recordsLinked to original sources
PubMed2006

Relative immunogenicity of Fya and K antigens in a Caucasian population, based on HLA class II restriction analysis.

BACKGROUND: It has long been known that relative immunogenicity is a characteristic of protein red blood cell (RBC) antigens, but the mechanisms remain unclear. The aim of this work was to elucidate the mechanisms underlying this relative immunogenicity. STUDY DESIGN AND METHODS: Two RBC antigens were used as a model--the highly immunogenic K antigen (KEL1) and the less immunogenic Fya antigen (FY1)--and analyzed the distribution of DRB1* molecules in two groups of Caucasian individuals producing anti-Fya (n = 29) or anti-K (n = 30) alloantibodies. These experimental results were compared to the results generated by TEPITOPE, a DRB1* peptide-binding motif prediction algorithm. RESULTS: It was found that within the anti-Fya group, the DRB1*04 phenotypic frequency was 100 percent, indicating that the DRB1*04 molecule is the restriction molecule. In the anti-K group, numerous DRB1* molecules were identified, demonstrating a high degree of histocompatibility promiscuity, corresponding to the predominant molecules in the Caucasian population. These findings were confirmed by TEPITOPE. CONCLUSION: These results strongly suggest that protein RBC intrinsic immunogenicity depends on the distribution of DRB1* restriction molecules.

Algorithms↗
PubMed2005

Intravenous immunoglobulin for autoimmune thrombocytopenic purpura.

Severe autoimmune thrombocytopenic purpura is now commonly treated with high doses of intravenous immunoglobulins (IVIGs). Twenty-four years after this treatment was first demonstrated to be effective, several questions remain to be resolved. We review here current knowledge concerning the frequency and type of side effects and the likely mechanism of action of IVIGs. We suggest that the currently recommended dose of IVIG (2 g/kg) could be halved, that the total dose of IVIG should be administered as a single infusion, that nonresponders could be provided another equal dose on day 3, and that IVIG plus prednisolone should be considered the gold standard for treatment of the most severe forms of the disease. Treatment with anti-D immunoglobulin could be proposed as an alternative if the results recently obtained with high doses (75 microg/kg) are confirmed. Finally, because IVIG has only a transient effect, it cannot be considered a curative treatment for patients with chronic autoimmune thrombocytopenic purpura.

Chronic Disease↗
PubMed2005

Platelet and granulocyte alloimmunisation in multitransfused Tunisian patients.

We determined the frequency of post-transfusion alloimmunisation against platelet and granulocyte antigens in 51 Tunisian polytransfused patients with haematological diseases. Serum samples were analysed by a standard and an antiglobulin-augmented lymphocytotoxicity technique, a granulocyte agglutination test, a granulocyte immunofluorescence test, a platelet immunofluorescence test and the monoclonal antibody-specific immobilisation of platelet antigens assay. No granulocyte-specific antibodies were detected. HLA antibodies were found in 58.8% of patients. Platelet-specific antibodies were detected in four patients and were directed against human platelet antigen (HPA)-5b, HPA-1b and HPA-3a. The three patients with Glanzmann's thrombasthenia developed anti-GPIIb/IIIa antibodies. This study provides immunogenetic information that could improve the management of transfusion therapy in Tunisia.

Autoantibodies↗
PubMed2005

Assessment of a therapeutic strategy for adults with severe autoimmune thrombocytopenic purpura based on a bleeding score rather than platelet count.

BACKGROUND AND OBJECTIVES: The optimal treatment for patients with autoimmune thrombocytopenic purpura (AITP) and a platelet count < or =20x10(9)/L is intravenous immunoglobulin (IVIg) but this treatment is expensive and steroids are a good alternative in less severe cases. Since the occurrence of life-threatening hemorrhage in adult AITP is a rare event, the aim of our study was to validate a therapeutic strategy based on a bleeding score for the short-term management of adults with AITP and a platelet count < or =20x10(9)/L. DESIGN AND METHODS: We developed a method to quantify hemorrhage in adults with AITP. Bleeding severity was graded on a numerical scale based on physical examination. When the bleeding score was < or =8, the patients were treated with steroids alone. For scores >8, patients received IVIg (1 to 2 g/kg) in combination with oral steroids. A good response was defined as the lowering of the initial bleeding score within 2 days after treatment initiation regardless of the platelet count. RESULTS: We applied this strategy for the management of 60 consecutive adults (mean age 48+/-23 years) with AITP and a platelet count < or =20x10(9)/L/L (mean platelet count 6+/-5x10(9)/L/L). Based on this strategy, IVIg was required in only 50% of the patients and no life-threatening bleeding occurred in patients treated with steroids alone. INTERPRETATION AND CONCLUSIONS: A therapeutic strategy based on a bleeding score rather than the platelet count appears to be relevant and safe and is a good IVIg-sparing strategy.

Adolescent↗
PubMed2004

Autoimmune thrombocytopenic purpura and common variable immunodeficiency: analysis of 21 cases and review of the literature.

To describe the main characteristics and outcome of autoimmune thrombocytopenic purpura (AITP) in patients with common variable immunodeficiency (CVID), we analyzed data from 21 patients and reviewed additional cases from the literature. To be included in this study, patients had to have CVID and a previous history of AITP with a platelet count < or = 50 x 10(9)/L at onset. A complete response to treatment was defined by a platelet count > or = 150 x 10(9)/L, and a partial response by a platelet count >>50 x 10(9)/L with an increase of at least twofold the initial level. The median platelet count at AITP diagnosis was 20 x 10(9)/L (range, 2-50 x 10(9)/L). The median age at AITP diagnosis was 23 years (range, 1-51 yr), whereas the median age at CVID diagnosis was 27 years (range, 10-74 yr). CVID was diagnosed before the onset of AITP in only 4 patients (19%), 3 of whom were being treated with intravenous immunoglobulin (i.v.Ig) replacement therapy. CVID was diagnosed more than 6 months after AITP in 13 cases (62%), and the 2 conditions were diagnosed concomitantly in 4 cases. Eleven patients (52%) had at least 1 autoimmune manifestation other than AITP, among which autoimmune hemolytic anemia (7 cases) and autoimmune neutropenia (5 cases) were preeminent. Seventeen of the 21 patients (80%) received at least 1 treatment for AITP; 13 patients received corticosteroids alone and 7 (54%) achieved at least a partial response; 8 patients received i.v.Ig at 1-2 g/kg alone or in combination with steroids, leading to a short-term response rate of 50%. Four patients underwent a splenectomy (2 complete responses, 2 failures); 2 additional splenectomies were performed for associated autoimmune hemolytic anemia. With a mean follow-up of 5.6 years after the surgical procedure, none of the 6 splenectomized patients had a life-threatening infection. With a median follow-up after AITP onset of 12 years, 13/21 patients (62%) were in treatment-free remission (7 complete responses, 6 partial responses), 7 patients (23%) were in remission while on prednisone < or = 20 mg/day with or without azathioprine, and only 1 patient still had a platelet count <50 x 10(9)/L. Five patients had died at the time of the analysis; none of the deaths was related to a hemorrhage. Severe infections including 3 fatal bacterial infections and 2 opportunistic infections occurred in 6 patients during or after treatment of AITP. In conclusion, AITP, alone or in combination with autoimmune hemolytic anemia (Evans syndrome) and/or autoimmune neutropenia, is frequent in patients with CVID, and is not prevented by i.v.Ig substitutive therapy. Since AITP frequently precedes the diagnosis of CVID, testing for immunoglobulin levels should be performed in every patient diagnosed with AITP. Steroids and splenectomy seem to have the same efficacy as in idiopathic AITP, but the increased risk of severe infections must be taken into consideration.

Adolescent↗
PubMed2002

Autoimmune thrombocytopenic Purpura and Helicobacter pylori infection.

BACKGROUND: The mechanisms triggering the production of platelet autoantibodies in autoimmune thrombocytopenic purpura (AITP) are poorly understood. Recently, marked improvements in platelet counts have been reported in patients with AITP and concurrent Helicobacter pylori infection after eradication of H pylori by a standard antibiotic regimen. We looked for an association between H pylori infection and AITP in adults. METHODS: Fifty-one adults of white French origin, negative for human immunodeficiency virus (mean +/- SD age, 40 +/- 19.8 years), with AITP and a platelet count of less than 50 x 10(3)/microL at onset were included. Thirty-five consecutive nonthrombocytopenic patients (mean +/- SD age, 43 +/- 22 years) of the same origin and with unknown H pylori status served as control subjects. Antibodies against H pylori were detected by means of an agglutination method in both patients and control subjects. Sex ratio, mean age, hemorrhagic manifestations, response to corticosteroid therapy, and final outcome were compared in H pylori-negative and H pylori-positive patients with AITP. To test for a possible molecular mimicry mechanism, we also used an immunoblot assay to look for specific H pylori antibodies in platelet eluates from 3 H pylori-positive patients with AITP. RESULTS: Seroprevalence of H pylori in patients with AITP (15 [29%]) was not significatively different from that in control subjects (10 [29%]). The H pylori-positive and H pylori-negative patients with AITP did not differ in main characteristics at AITP onset, response rate to corticosteroids, and final outcome. None of the 3 patients investigated had H pylori antibodies in platelet eluates. CONCLUSION: Although the role of H pylori in a subgroup of patients with AITP cannot be excluded, we found no evidence of an association between H pylori infection and AITP.

Adult↗
PubMed2002

Long-term kidney graft survival across a positive historic but negative current sensitized cross-match.

BACKGROUND: The sensitive cross-match (XM) techniques that have been introduced for clinical transplantation can detect anti-donor immune reactivity despite a negative standard National Institute of Health (NIH) cross-match. One of them uses anti-kappa human light chain globulins (AHG). But there is some discussion about the clinical consequences of a positive AHG-XM in the historical sera that became negative in the sera collected just before the transplantation (pretransplant sera). This study was intended to assess the risk of kidney graft failure associated with a positive historic but negative pretransplant AHG-XM in allosensitized patients having a negative historic NIH-XM. METHODS: This retrospective study includes 90 consecutive renal transplants in immunized patients performed at one center between 1985 and 1991. All of the patients had negative historical and pretransplant standard NIH lymphocytotoxic cross-matches and received the same immunosuppressive regimen. The AHG-XMs were done retrospectively using peak historic and sera collected on the day of the transplantation. RESULTS: The AHG cross-match (AHG-XM) was positive in 17 patients, although the standard NIH cross-match was negative. Fourteen of them had a positive historical but negative pretransplant AHG-XM. The actuarial graft survival in this group of 14 patients was 100% at 1 year and 78% at 9 years compared with 90 and 67%, respectively, in patients with negative historical AHG-XM. In addition, the number of rejection episodes per patient as well as renal function at 1, 2, and 5 years were similar in the two groups. IgG anti-donor HLA class I accounted for the XM positivity in 12 of the 14 patients; most rapidly lost all antibody reactivity by NIH technique in an average time of 8 months before the transplantation. In conclusion, this study suggests that transplant patients having a negative historic NIH-XM but a positive historic AHG-XM may not be at high risk of graft failure especially if there is a well-documented sera history showing a marked decrease in PRA level before transplantation and a negative pretransplant AHG-XM.

Adult↗
PubMed2002

Intravenous immunoglobulin or high-dose methylprednisolone, with or without oral prednisone, for adults with untreated severe autoimmune thrombocytopenic purpura: a randomised, multicentre trial.

BACKGROUND: Treatment of adults with autoimmune thrombocytopenic purpura (AITP) is based more on individual experience than on results of controlled studies. We compared intravenous immunoglobulin with high-dose methylprednisolone in untreated adults with severe AITP and assessed efficacy of subsequent oral steroids compared with placebo. Primary outcome was number of days with platelet count greater than 50 x 10(9)/L within the first 21 days. METHODS: We did a randomised multicentre trial based on a 232 design. 122 adults with severe AITP (platelet count < or =20 x 10(9)/L) were randomly assigned to receive either intravenous immunoglobulin or high-dose methylprednisolone on days 1-3 (randomisation A), and then to receive either oral prednisone or placebo (randomisation B) on days 4-21. Analysis was by intention to treat. FINDINGS: Six patients were excluded from the analysis. The number of days on which platelet counts were above 50 x 10(9)/L was 18 in 56 patients receiving intravenous immunoglobulin and 14 in 60 receiving high-dose methylprednisolone (p=0.02). Percentage of patients who had platelet counts over 50 x 10(9)/L on days 2 and 5 was 7% and 79%, respectively, in the intravenous immunoglobulin group compared with 2% and 60%, respectively, in the high-dose methylprednisolone group (p=0.04). During the second treatment period, prednisone was more effective than placebo for all short-term endpoints. Patients who received intravenous immunoglobulin and prednisone had platelet count greater than 50 x 10(9)/L for 18.5 days (p=0.005), and those treated with high-dose methylprednisolone and prednisone had this count for 17.5 days. INTERPRETATION: Intravenous immunoglobulin and oral prednisone seems to be more effective than high-dose methylprednisolone and oral prednisone in adults with severe AITP, although the latter treatment is effective and well tolerated.

Adult↗
PubMed2002

Platelet autoantibodies and lupus-associated thrombocytopenia.

To characterize the antigenic targets of anti-platelet antibodies (APA) found in systemic lupus erythematosus (SLE)-associated thrombocytopenia, 48 patients with immune thrombocytopenia and SLE were compared with 20 patients with SLE who had never been thrombocytopenic. Both cases and controls were tested for circulating APA by an indirect platelet suspension immunofluorescence assay (PSIIFT) and by indirect monoclonal antibody specific immobilization of platelet antigens (MAIPA). A direct platelet suspension immunofluorescence assay (PSIFT) was also used for antibodies bound to platelets in vivo in thrombocytopenic patients; 13 of them with high titres of platelets-bound APA were investigated by direct and indirect MAIPA and platelet eluate analysis. Circulating APA were detected by PSIIFT in 88% of cases and 55% of controls (P = 0.0066) and platelet-bound antibodies were detected by PSIFT in 90% of cases. Indirect MAIPA detected specific APA (mainly directed against GpIIbIIIa) in 36% of cases and only 5% of the controls (P = 0.0076). Nine out of the 13 fully investigated thrombocytopenic patients (69%) had a positive direct MAIPA and/or APA detected in platelet eluates. In conclusion, the production of specific anti-platelet autoantibodies, mainly directed against GpIIb/IIIa, and their binding to platelet membrane plays an important role in the pathogenesis of SLE-associated thrombocytopenia.

Adult↗
PubMed2002

Treatment of severe immune thrombocytopenia associated with systemic lupus erythematosus: 59 cases.

OBJECTIVE: To evaluate the response to treatment in a large cohort of patients with systemic lupus erythematosus (SLE) associated with autoimmune thrombocytopenia. METHODS: Response to treatment was assessed retrospectively in 59 patients with SLE, either definite (n = 44) or incomplete (n = 15), associated with frank autoimmune thrombocytopenia (defined as platelet count < 50 x 10(9)/l). Response to treatment was classified as complete (CR: platelet count > 150 x 10(9)/l), partial (PR: platelet count > 50 x 10/l), or failure (FR) in the other cases. RESULTS: Oral prednisone alone was used in 50 of the 59 patients (mean initial dose 1 mg/kg body weight/day). A response was obtained in 80% of cases (CR in 28. PR in 12) but only 11 (22%) had a sustained response (CR, n = 7; PR, n = 4). In contrast, combined treatment with prednisone and either danazol (n = 18) or hydroxychloroquine (n = 11) resulted in 50% (7 CR, 2 PR) and 64% (4 CR, 3 PR) longterm responses, respectively, allowing prednisone to be withdrawn or the dose tapered below 0.2 mg/kg body weight/day. High dose methylprednisolone pulses (n = 10) and intravenous immunoglobulin (IVIG) (n = 31) resulted in positive responses in 60% (4 CR, 2 PR) and 65% (12 CR, 8 PR) of cases, respectively, but the response was transient in each case. Splenectomy (n = 17) resulted in 65% longterm responses (10 CR, 1 PR). Only 2 longterm partial responses were obtained with the 22 immunosuppressant-containing regimens administered to 14 patients. At the end of the study. a response was observed in 52 (88%) patients [CR: 36 (61%), PR: 16 (27%)], mainly as a result of splenectomy or combined treatment with prednisone and either danazol or hydroxychloroquine. CONCLUSION: Longterm remission was obtained in the majority of patients. The major treatments inducing remission were splenectomy and prednisone combined with danazol or hydroxychloroquine.

Adolescent↗