61 autologous transplantations for haematological malignancies have been performed with periphera... more 61 autologous transplantations for haematological malignancies have been performed with peripheral blood stem cells in 60 patients. 26 grafts were performed for non-Hodgkin's lymphoma (18 patients were transplanted in first remission, 8 patients after progression or relapse), 13 for multiple myeloma, 7 for Hodgkin's disease and 10 for acute myeloid leukaemia. One patient died from thrombosis of the portal vein. 38 patients were in complete remission 29 months (extremes: 14-44) after transplantation. 21 of 60 patients progressed or relapsed after transplantation, and 14 died. No death was attributed to graft failure, infection or haemorrhage. In conclusion, transplantation with peripheral blood stem cells is well tolerated, has a low toxicity rate, and can be used safely for patients with haematological malignancies.
Journal de Gynécologie Obstétrique et Biologie de la Reproduction
Perinatal hemolytic disease is characterized by the destruction of fetal red blood cells by mater... more Perinatal hemolytic disease is characterized by the destruction of fetal red blood cells by maternal antibodies directed against membrane antigens and can lead to immune fetal hydrops. More than 250 blood group antigens have been described. After considering the particular situation of ABO incompatibility, this article describes the classification of red blood cells antigens, with particular reference to the Rhesus system. Other antigens such as Kell, Kidd, Duffy, MNSs, P and Lutheran are also considered.
Journal de Gynécologie Obstétrique et Biologie de la Reproduction
There has been a dramatic reduction in the incidence of neonatal mortality due to fetal hemolytic... more There has been a dramatic reduction in the incidence of neonatal mortality due to fetal hemolytic disease since the introduction of Rhesus prophylaxis. Although routinely used since 1968, the exact mode of action of anti-D IgGs is still not fully understood. Notable advances have taken place in the screening and the management of fetal hemolytic disease. This article describes the antibody detection in the mother, and the fetal management with ultrasound amniocentesis, fetal blood sampling and intrauterine transfusions. Finally, the postnatal management is also considered.
Three patients presented a unique syndrome of recurrent panniculitis with an IgGkappa paraprotein... more Three patients presented a unique syndrome of recurrent panniculitis with an IgGkappa paraprotein and depletion of the early components of the classical pathway of complement. The IgGkappa paraproteins were monomers with a normal structure, and with no evidence for aggregation, as assessed by electron microscopy and ultracentrifugation. Both heavy and light chains were of normal molecular size (SDS-PAGE), and the paraproteins were not heavily glycosylated. However, the paraproteins from all three patients had unusual features that included abnormal behavior on gel filtration chromatography and a heavy chain of high pI. When analyzed by fast protein liquid chromatography (Superdex 200), elution of the paraproteins was retarded, particularly when the ionic strength was increased. This retardation was partially reversed in 20% alcohol, and fully reversed in 6 M guanidine-HCl. Neither anti-C1 inhibitor nor anti-C1q autoantibodies were found in any of the patients' sera. However, the...
Should we treat iron deficiency without anemia? The simple fact that the question can be formulat... more Should we treat iron deficiency without anemia? The simple fact that the question can be formulated already leads to controversies. During the past years, the development of a new formulation of intravenous iron has helped fuel the controversy. What is the situation in 2012? This article gives a practical point of view on the actual situation and provides indications on the use of new intravenous medications.
Iron deficiency is generally investigated when faced with anemia, or with symptoms that could be ... more Iron deficiency is generally investigated when faced with anemia, or with symptoms that could be related to iron deficiency without anemia. This simple disorder is easy to treat, provided that the diagnosis is correct. Several biological tests are available, but their interpretation is oftentimes problematic. Pre-analytical factors can interfere with measurements, normal values can change depending on suppliers, and, above all, results from different markers can be contradictory in some clinical situations. The aim of this article is to evaluate how the evolution of scientific knowledge and clinical trials can contribute to a better understanding and greater reliability in the diagnosis of iron deficiency.
The age of erythrocyte concentrates (EC) in transfusion medicine and the adverse outcomes when tr... more The age of erythrocyte concentrates (EC) in transfusion medicine and the adverse outcomes when transfusing long-term-stored EC are highly controversial issues. Whereas the definition of a short-term-stored EC or a long-term-stored EC is unclear in clinical trials, data based on in vitro storage assays can help defining a limit in addition of the expiration date. The present review merges together these data in order to highlight an EC age cut-off and points out potential misleading consideration. The analysis of in vitro data highlights the presence of reversible and irreversible storage lesions and demonstrates that red blood cells (RBC) exhibit two limits during storage: one around 2 weeks and another one around 4 weeks of storage. Of particular importance, the first lesions to appear, i.e. the reversible ones, are per se reversible once transfused, whereas the irreversible lesions are not. In clinical trials, the EC age cut-off for short-term storage is in general fewer than 14 days (11 ± 4 days) and more disperse for long-term-stored EC (17 ± 13 days), regardless the clinical outcomes. Taking together, EC age cut-off in clinical trials does not totally fall into line of in vitro aging data, whereas it is the key criteria in clinical studies. Long-term-stored EC considered in clinical trials are not probably old enough to answer the question: "Does transfusion of long-term-stored EC (older than 4 weeks) result in worse clinical outcomes?" Depending on ethical concerns and clinical practices, older EC than currently assayed in clinical trials should have to be considered. These two worlds trying to understand the aging of erythrocytes and the impact on patients do not seem to speak the same language.
... David Crettaz, Lynne Thadikkaran, Denis Gallot, Pierre-Alain Queloz, Vincent Sapin, Joël S. R... more ... David Crettaz, Lynne Thadikkaran, Denis Gallot, Pierre-Alain Queloz, Vincent Sapin, Joël S. Rossier, Patrick Hohlfeld, and Jean-Daniel Tissot ... Jauniaux E, Jurkovic D, Gulbis B, Liesnard C, Lees C, Campbell S. Materno-fetal immunoglobulin transfer and passive immunity during ...
Platelet inactivation technologies (PITs) have been shown to increase platelet storage lesions (P... more Platelet inactivation technologies (PITs) have been shown to increase platelet storage lesions (PSLs). This study investigates amotosalen/ultraviolet (UV)A- and riboflavin/UVB-induced platelet (PLT) lesions in vitro. Particular attention is given to the effect of UVB alone on PLTs. Buffy coat-derived PLT concentrates (PCs) were treated with amotosalen/UVA, riboflavin/UVB, or UVB alone and compared to untreated PCs throughout storage. In vitro PLT function was assessed by blood gas and metabolite analyses, flow cytometry-based assays (CD62P, JC-1, annexin V, PAC-1), hypotonic shock response, and static adhesion to fibrinogen-coated wells. In our experimental conditions, riboflavin/UVB-treated PCs showed the most pronounced differences compared to untreated and amotosalen/UVA-treated PCs. The riboflavin/UVB treatment led to a significant increase of anaerobic glycolysis rate despite functional mitochondria, a significant increase of CD62P on Day 2, and a decrease of JC-1 aggregates an...
Blood transfusion = Trasfusione del sangue, Jan 23, 2014
The Intercept Blood System(TM) (Cerus) is used to inactivate pathogens in platelet concentrates (... more The Intercept Blood System(TM) (Cerus) is used to inactivate pathogens in platelet concentrates (PC). The aim of this study was to elucidate the extent to which the Intercept treatment modifies the functional properties of platelets. A two-arm study was conducted initially to compare buffy coat-derived pathogen-inactivated PC to untreated PC (n=5) throughout storage. A four-arm study was then designed to evaluate the contribution of the compound adsorbing device (CAD) and ultraviolet (UV) illumination to the changes observed upon Intercept treatment. Intercept-treated PC, CAD-incubated PC, and UV-illuminated PC were compared to untreated PC (n=5). Functional characteristics were assessed using flow cytometry, hypotonic shock response (HSR), aggregation, adhesion assays and flow cytometry for the detection of CD62P, CD42b, GPIIb-IIIa, phosphatidylserine exposure and JC-1 aggregates. Compared to fresh platelets, end-of-storage platelets exhibited greater passive activation, disruption...
Q fever is a worldwide zoonotic infectious disease due to Coxiella burnetii. The clinical present... more Q fever is a worldwide zoonotic infectious disease due to Coxiella burnetii. The clinical presentation may be acute (pneumonia and/or hepatitis) or chronic (most commonly endocarditis). Diagnosis mainly relies on serology and PCR. We therefore developed a quantitative real-time PCR. We first tested blindly its performance on various clinical samples and then, when thoroughly validated, we applied it during a 7-year period for the diagnosis of both acute and persistent C. burnetii infection. Analytical sensitivity (< 10 copies/PCR) was excellent. When tested blindly on 183 samples, the specificity of the PCR was 100% (142/142) and the sensitivity was 71% (29/41). The sensitivity was 88% (7/8) on valvular samples, 69% (20/29) on blood samples and 50% (2/4) on urine samples. This new quantitative PCR was then successfully applied for the diagnosis of acute Q fever and endovascular infection due to C. burnetii, allowing the diagnosis of Q fever in six patients over a 7-year period. D...
Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur̈ Transfusionsmedizin und Immunham̈atologie, 2014
A revolution occurred during the last decade in the comprehension of the physiology as well as in... more A revolution occurred during the last decade in the comprehension of the physiology as well as in the physiopathology of iron metabolism. The purpose of this review is to summarize the recent knowledge that has accumulated, allowing a better comprehension of the mechanisms implicated in iron homeostasis. Iron metabolism is very fine tuned. The free molecule is very toxic; therefore, complex regulatory mechanisms have been developed in mammalian to insure adequate intestinal absorption, transportation, utilization, and elimination. 'Ironomics' certainly will be the future of the understanding of genes as well as of the protein-protein interactions involved in iron metabolism.
We describe the case of a 30-year-old man with a severe autoimmune disease characterized by cryog... more We describe the case of a 30-year-old man with a severe autoimmune disease characterized by cryoglobulinaemia, pulmonary hypertension, Raynaud's phenomenon, lymphadenopathy, and glomerulonephritis. Despite initial remission following autologous stem cell transplantation, his disease relapsed and he died from pulmonary hypertension. At presentation the patient had hypergammaglobulinaemia and a number of autoantibodies, including rheumatoid factor (1:10240). The most striking feature was the extremely high level of cryoglobulins. The cryoprecipitate consisted of polyclonal IgM, IgG and albumin. Interestingly, the albumin in the cryoprecipitate was exclusively present in SS-bonded oligomeric forms, and contained an abnormal acidic component as judged by 2D gel electrophoresis. Oxidized albumin was also present in serum, and represented a small but significant fraction. None of the many known albumin variants have so far been associated with a particular disease; thus our results ma...
Two episodes of severe panniculitis accompanied by fever and an acute phase response were the mai... more Two episodes of severe panniculitis accompanied by fever and an acute phase response were the main clinical features in a patient who had an unusual IgG kappa paraprotein. Both episodes responded promptly to steroids. Complement proteins of the early classical pathway were depleted in the patient's serum, and in vitro experiments indicated that the IgG kappa paraprotein activated complement directly. The association of recurrent panniculitis and paraproteinemia-hypocomplementemia has been described in 2 other patients. It should be recognized since its response to steroids is immediate.
Chronic alcohol abuse alters the normal N-glycosylation of transferrin, producing the carbohydrat... more Chronic alcohol abuse alters the normal N-glycosylation of transferrin, producing the carbohydrate-deficient transferrin isoforms. This alteration could be similar to that present in patients with carbohydrate-deficient glycoprotein syndrome type 1 (CDG1). We thus compared the alterations of N-glycans present in patients with alcoholism and patients with CDG1. The N-glycans of serum glycoproteins were compared in sera of patients with alcoholism, patients with CDG1, and controls by two-dimensional electrophoresis, neuraminidase, peptide:N-glycosidase F, and endoglycosidase F2 treatments. A specific antibody directed against the amino acid sequence surrounding the N-432 N-glycosylation site of transferrin was prepared (SZ-350 antibody). In patients with alcoholism, the abnormal transferrin and alpha(1)-antitrypsin isoforms were devoid of a variable number of entire N-glycan moieties and were identical with those present in CDG1. In the serum of patients with alcoholism, this finding ...
61 autologous transplantations for haematological malignancies have been performed with periphera... more 61 autologous transplantations for haematological malignancies have been performed with peripheral blood stem cells in 60 patients. 26 grafts were performed for non-Hodgkin's lymphoma (18 patients were transplanted in first remission, 8 patients after progression or relapse), 13 for multiple myeloma, 7 for Hodgkin's disease and 10 for acute myeloid leukaemia. One patient died from thrombosis of the portal vein. 38 patients were in complete remission 29 months (extremes: 14-44) after transplantation. 21 of 60 patients progressed or relapsed after transplantation, and 14 died. No death was attributed to graft failure, infection or haemorrhage. In conclusion, transplantation with peripheral blood stem cells is well tolerated, has a low toxicity rate, and can be used safely for patients with haematological malignancies.
Journal de Gynécologie Obstétrique et Biologie de la Reproduction
Perinatal hemolytic disease is characterized by the destruction of fetal red blood cells by mater... more Perinatal hemolytic disease is characterized by the destruction of fetal red blood cells by maternal antibodies directed against membrane antigens and can lead to immune fetal hydrops. More than 250 blood group antigens have been described. After considering the particular situation of ABO incompatibility, this article describes the classification of red blood cells antigens, with particular reference to the Rhesus system. Other antigens such as Kell, Kidd, Duffy, MNSs, P and Lutheran are also considered.
Journal de Gynécologie Obstétrique et Biologie de la Reproduction
There has been a dramatic reduction in the incidence of neonatal mortality due to fetal hemolytic... more There has been a dramatic reduction in the incidence of neonatal mortality due to fetal hemolytic disease since the introduction of Rhesus prophylaxis. Although routinely used since 1968, the exact mode of action of anti-D IgGs is still not fully understood. Notable advances have taken place in the screening and the management of fetal hemolytic disease. This article describes the antibody detection in the mother, and the fetal management with ultrasound amniocentesis, fetal blood sampling and intrauterine transfusions. Finally, the postnatal management is also considered.
Three patients presented a unique syndrome of recurrent panniculitis with an IgGkappa paraprotein... more Three patients presented a unique syndrome of recurrent panniculitis with an IgGkappa paraprotein and depletion of the early components of the classical pathway of complement. The IgGkappa paraproteins were monomers with a normal structure, and with no evidence for aggregation, as assessed by electron microscopy and ultracentrifugation. Both heavy and light chains were of normal molecular size (SDS-PAGE), and the paraproteins were not heavily glycosylated. However, the paraproteins from all three patients had unusual features that included abnormal behavior on gel filtration chromatography and a heavy chain of high pI. When analyzed by fast protein liquid chromatography (Superdex 200), elution of the paraproteins was retarded, particularly when the ionic strength was increased. This retardation was partially reversed in 20% alcohol, and fully reversed in 6 M guanidine-HCl. Neither anti-C1 inhibitor nor anti-C1q autoantibodies were found in any of the patients' sera. However, the...
Should we treat iron deficiency without anemia? The simple fact that the question can be formulat... more Should we treat iron deficiency without anemia? The simple fact that the question can be formulated already leads to controversies. During the past years, the development of a new formulation of intravenous iron has helped fuel the controversy. What is the situation in 2012? This article gives a practical point of view on the actual situation and provides indications on the use of new intravenous medications.
Iron deficiency is generally investigated when faced with anemia, or with symptoms that could be ... more Iron deficiency is generally investigated when faced with anemia, or with symptoms that could be related to iron deficiency without anemia. This simple disorder is easy to treat, provided that the diagnosis is correct. Several biological tests are available, but their interpretation is oftentimes problematic. Pre-analytical factors can interfere with measurements, normal values can change depending on suppliers, and, above all, results from different markers can be contradictory in some clinical situations. The aim of this article is to evaluate how the evolution of scientific knowledge and clinical trials can contribute to a better understanding and greater reliability in the diagnosis of iron deficiency.
The age of erythrocyte concentrates (EC) in transfusion medicine and the adverse outcomes when tr... more The age of erythrocyte concentrates (EC) in transfusion medicine and the adverse outcomes when transfusing long-term-stored EC are highly controversial issues. Whereas the definition of a short-term-stored EC or a long-term-stored EC is unclear in clinical trials, data based on in vitro storage assays can help defining a limit in addition of the expiration date. The present review merges together these data in order to highlight an EC age cut-off and points out potential misleading consideration. The analysis of in vitro data highlights the presence of reversible and irreversible storage lesions and demonstrates that red blood cells (RBC) exhibit two limits during storage: one around 2 weeks and another one around 4 weeks of storage. Of particular importance, the first lesions to appear, i.e. the reversible ones, are per se reversible once transfused, whereas the irreversible lesions are not. In clinical trials, the EC age cut-off for short-term storage is in general fewer than 14 days (11 ± 4 days) and more disperse for long-term-stored EC (17 ± 13 days), regardless the clinical outcomes. Taking together, EC age cut-off in clinical trials does not totally fall into line of in vitro aging data, whereas it is the key criteria in clinical studies. Long-term-stored EC considered in clinical trials are not probably old enough to answer the question: &amp;amp;amp;amp;amp;amp;quot;Does transfusion of long-term-stored EC (older than 4 weeks) result in worse clinical outcomes?&amp;amp;amp;amp;amp;amp;quot; Depending on ethical concerns and clinical practices, older EC than currently assayed in clinical trials should have to be considered. These two worlds trying to understand the aging of erythrocytes and the impact on patients do not seem to speak the same language.
... David Crettaz, Lynne Thadikkaran, Denis Gallot, Pierre-Alain Queloz, Vincent Sapin, Joël S. R... more ... David Crettaz, Lynne Thadikkaran, Denis Gallot, Pierre-Alain Queloz, Vincent Sapin, Joël S. Rossier, Patrick Hohlfeld, and Jean-Daniel Tissot ... Jauniaux E, Jurkovic D, Gulbis B, Liesnard C, Lees C, Campbell S. Materno-fetal immunoglobulin transfer and passive immunity during ...
Platelet inactivation technologies (PITs) have been shown to increase platelet storage lesions (P... more Platelet inactivation technologies (PITs) have been shown to increase platelet storage lesions (PSLs). This study investigates amotosalen/ultraviolet (UV)A- and riboflavin/UVB-induced platelet (PLT) lesions in vitro. Particular attention is given to the effect of UVB alone on PLTs. Buffy coat-derived PLT concentrates (PCs) were treated with amotosalen/UVA, riboflavin/UVB, or UVB alone and compared to untreated PCs throughout storage. In vitro PLT function was assessed by blood gas and metabolite analyses, flow cytometry-based assays (CD62P, JC-1, annexin V, PAC-1), hypotonic shock response, and static adhesion to fibrinogen-coated wells. In our experimental conditions, riboflavin/UVB-treated PCs showed the most pronounced differences compared to untreated and amotosalen/UVA-treated PCs. The riboflavin/UVB treatment led to a significant increase of anaerobic glycolysis rate despite functional mitochondria, a significant increase of CD62P on Day 2, and a decrease of JC-1 aggregates an...
Blood transfusion = Trasfusione del sangue, Jan 23, 2014
The Intercept Blood System(TM) (Cerus) is used to inactivate pathogens in platelet concentrates (... more The Intercept Blood System(TM) (Cerus) is used to inactivate pathogens in platelet concentrates (PC). The aim of this study was to elucidate the extent to which the Intercept treatment modifies the functional properties of platelets. A two-arm study was conducted initially to compare buffy coat-derived pathogen-inactivated PC to untreated PC (n=5) throughout storage. A four-arm study was then designed to evaluate the contribution of the compound adsorbing device (CAD) and ultraviolet (UV) illumination to the changes observed upon Intercept treatment. Intercept-treated PC, CAD-incubated PC, and UV-illuminated PC were compared to untreated PC (n=5). Functional characteristics were assessed using flow cytometry, hypotonic shock response (HSR), aggregation, adhesion assays and flow cytometry for the detection of CD62P, CD42b, GPIIb-IIIa, phosphatidylserine exposure and JC-1 aggregates. Compared to fresh platelets, end-of-storage platelets exhibited greater passive activation, disruption...
Q fever is a worldwide zoonotic infectious disease due to Coxiella burnetii. The clinical present... more Q fever is a worldwide zoonotic infectious disease due to Coxiella burnetii. The clinical presentation may be acute (pneumonia and/or hepatitis) or chronic (most commonly endocarditis). Diagnosis mainly relies on serology and PCR. We therefore developed a quantitative real-time PCR. We first tested blindly its performance on various clinical samples and then, when thoroughly validated, we applied it during a 7-year period for the diagnosis of both acute and persistent C. burnetii infection. Analytical sensitivity (< 10 copies/PCR) was excellent. When tested blindly on 183 samples, the specificity of the PCR was 100% (142/142) and the sensitivity was 71% (29/41). The sensitivity was 88% (7/8) on valvular samples, 69% (20/29) on blood samples and 50% (2/4) on urine samples. This new quantitative PCR was then successfully applied for the diagnosis of acute Q fever and endovascular infection due to C. burnetii, allowing the diagnosis of Q fever in six patients over a 7-year period. D...
Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur̈ Transfusionsmedizin und Immunham̈atologie, 2014
A revolution occurred during the last decade in the comprehension of the physiology as well as in... more A revolution occurred during the last decade in the comprehension of the physiology as well as in the physiopathology of iron metabolism. The purpose of this review is to summarize the recent knowledge that has accumulated, allowing a better comprehension of the mechanisms implicated in iron homeostasis. Iron metabolism is very fine tuned. The free molecule is very toxic; therefore, complex regulatory mechanisms have been developed in mammalian to insure adequate intestinal absorption, transportation, utilization, and elimination. 'Ironomics' certainly will be the future of the understanding of genes as well as of the protein-protein interactions involved in iron metabolism.
We describe the case of a 30-year-old man with a severe autoimmune disease characterized by cryog... more We describe the case of a 30-year-old man with a severe autoimmune disease characterized by cryoglobulinaemia, pulmonary hypertension, Raynaud's phenomenon, lymphadenopathy, and glomerulonephritis. Despite initial remission following autologous stem cell transplantation, his disease relapsed and he died from pulmonary hypertension. At presentation the patient had hypergammaglobulinaemia and a number of autoantibodies, including rheumatoid factor (1:10240). The most striking feature was the extremely high level of cryoglobulins. The cryoprecipitate consisted of polyclonal IgM, IgG and albumin. Interestingly, the albumin in the cryoprecipitate was exclusively present in SS-bonded oligomeric forms, and contained an abnormal acidic component as judged by 2D gel electrophoresis. Oxidized albumin was also present in serum, and represented a small but significant fraction. None of the many known albumin variants have so far been associated with a particular disease; thus our results ma...
Two episodes of severe panniculitis accompanied by fever and an acute phase response were the mai... more Two episodes of severe panniculitis accompanied by fever and an acute phase response were the main clinical features in a patient who had an unusual IgG kappa paraprotein. Both episodes responded promptly to steroids. Complement proteins of the early classical pathway were depleted in the patient's serum, and in vitro experiments indicated that the IgG kappa paraprotein activated complement directly. The association of recurrent panniculitis and paraproteinemia-hypocomplementemia has been described in 2 other patients. It should be recognized since its response to steroids is immediate.
Chronic alcohol abuse alters the normal N-glycosylation of transferrin, producing the carbohydrat... more Chronic alcohol abuse alters the normal N-glycosylation of transferrin, producing the carbohydrate-deficient transferrin isoforms. This alteration could be similar to that present in patients with carbohydrate-deficient glycoprotein syndrome type 1 (CDG1). We thus compared the alterations of N-glycans present in patients with alcoholism and patients with CDG1. The N-glycans of serum glycoproteins were compared in sera of patients with alcoholism, patients with CDG1, and controls by two-dimensional electrophoresis, neuraminidase, peptide:N-glycosidase F, and endoglycosidase F2 treatments. A specific antibody directed against the amino acid sequence surrounding the N-432 N-glycosylation site of transferrin was prepared (SZ-350 antibody). In patients with alcoholism, the abnormal transferrin and alpha(1)-antitrypsin isoforms were devoid of a variable number of entire N-glycan moieties and were identical with those present in CDG1. In the serum of patients with alcoholism, this finding ...
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Papers by Jean-daniel Tissot