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Analysis of ferritinemia and serum soluble interleukin-2 receptor α concentration in type 1 Gaucher disease
acta haematologica polonica 44s (2013) 180–181
Contents lists available at SciVerse ScienceDirect
Acta Haematologica Polonica journal homepage: www.elsevier.com/locate/achaem
Prezentacje plakatowe/Poster presentations
SESJA – Limfohistiocytoza hemofagocytarna
Analysis of ferritinemia and serum soluble interleukin-2 receptor a concentration in type 1 Gaucher disease F. Lorenz 1, A. Bulanda 2, G. Kleinotiene 3, A. Markuszewska-Kuczyńska 1,4, M. Machaczka 4,5,* 1 Department of Radiation Sciences, Section of Hematology, University of Umeå, Szwecja 2 Collegium Medicum of the Jagiellonian University, Kraków, Polska 3 Centre of Hematology and Oncology, Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Clinics, Wilno, Litwa 4 Hematology Center Karolinska, Karolinska Institutet, Karolinska University Hospital Huddinge, Sztokholm, Szwecja 5 Department of Medicine at Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Sztokholm, Szwecja *Presenting and corresponding author. E-mail address: [email protected]
Gaucher disease (GD) is a progressive, multisystem lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme, glucocerebrosidase (GBA), arising from autosomal recessive mutations in the GBA1 gene (1q21). According to the EU definition, GD belongs to so called ultra-rare diseases affecting less than 1 person/50,000 inhabitants. In Sweden, with a population of approximately 9.4 million people, the overall prevalence of GD is approximately 1:170,000 inhabitants. Patients with type 1 GD (GD1) suffer from an increased susceptibility to malignancies, and while the underlying mechanisms are not known, it is postulated to be associated with macrophage dysfunction and immune dysregulation in GD. The pathophysiology of hyperferritinemia in GD has not yet been elucidated and different mechanisms are possible, including the chronic inflammation hypothesis. Soluble interleukin-2 receptor a (sIL-2Ra) is released from activated T and B cells, monocytes and some malignant cells. To the best of our knowledge, only one previous study examined sIL-2Ra levels in GD, and none has studied it in correlation with ferritinemia. Objectives: This study was undertaken to evaluate serum ferritin and sIL-2Ra levels in untreated GD1 patients at diagnosis. Patients and Methods: Between 2002 and 2012, 13 patients were diagnosed with GD1 in the Stockholm area. In all of them, the diagnosis of GD was confirmed by a low activity of b-glucosidase in peripheral blood leukocytes and an increased activity of plasma chitotriosidase. Further direct DNA sequencing revealed mutations in the GBA1 gene in all cases. Serum ferritin levels (ref.: 30–350 mg/L) were routinely measured on all GD1 patients at diagnosis. Iron overload was defined as hyperferritinemia >500 mg/L. Serum levels of sIL-2Ra (ref.: 321–565 U/mL) were measured by ELISA, using the quantitative 'sandwich' enzyme immunoassay, on the IMMULITE® 1000 Immunoassay System (Siemens Medical Solutions Diagnostics, Tarrytown, NY, USA). The files were reviewed for the collection of relevant clinical data. Results: Elevated serum ferritin >500 mg/L was present in all but 1 patient (92%). Interestingly, all ethnic Swedish patients (7 persons) had significantly higher ferritin levels (median 1910 mg/L; range 1108–4408) as compared to non-ethnic Swedish patients (median 900 mg/L; range 81–1238). The median age of the ethnic Swedish patients at diagnosis was 30 years (range 3– 61 years); 3 of them were splenectomized and two of them developed Parkinson's disease. The median age of the non-ethnic Swedish GD1 patien 3 of them were splenectomized and two of them developed Parkinson's disease. The median age of the non-ethnic Swedish GD1 patients at diagnosis was 53 years (range 3–60 years); only one of them with the most severe phenotype and heterozygous private GBA1 mutations was splenectomized in Iran at the age of 5 years. None of the nonethnic Swedish GD1 patients developed Parkinson's disease. The median value of serum sIL-2Ra was 373 U/mL (range 249– 774) and it was within normal range in 92% patients (12/13).
0001-5814/$ – see front matter
acta haematologica polonica 44s (2013) 180–181
181
Conclusions: The study revealed that iron overload is common in GD1 patients in Sweden. It is possible that ethnic Swedish patients experience a more severe GD phenotype and have a somewhat higher risk of developing Parkinson's disease. Notably, unlike hemophagocytic lymphohistiocytosis, hyperferritinemia in GD1 is not associated with high serum levels of sIL-2Ra, which mainly reflects T cell activation. Thus, our results rather support an immunosuppressive effect of hyperferritinemia, which is in line with the observed increased susceptibility to malignancies in GD1. http://dx.doi.org/10.1016/j.achaem.2013.07.186
Contents lists available at SciVerse ScienceDirect
Acta Haematologica Polonica journal homepage: www.elsevier.com/locate/achaem
Prezentacje plakatowe/Poster presentations
SESJA – Limfohistiocytoza hemofagocytarna
Analysis of ferritinemia and serum soluble interleukin-2 receptor a concentration in type 1 Gaucher disease F. Lorenz 1, A. Bulanda 2, G. Kleinotiene 3, A. Markuszewska-Kuczyńska 1,4, M. Machaczka 4,5,* 1 Department of Radiation Sciences, Section of Hematology, University of Umeå, Szwecja 2 Collegium Medicum of the Jagiellonian University, Kraków, Polska 3 Centre of Hematology and Oncology, Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Clinics, Wilno, Litwa 4 Hematology Center Karolinska, Karolinska Institutet, Karolinska University Hospital Huddinge, Sztokholm, Szwecja 5 Department of Medicine at Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Sztokholm, Szwecja *Presenting and corresponding author. E-mail address: [email protected]
Gaucher disease (GD) is a progressive, multisystem lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme, glucocerebrosidase (GBA), arising from autosomal recessive mutations in the GBA1 gene (1q21). According to the EU definition, GD belongs to so called ultra-rare diseases affecting less than 1 person/50,000 inhabitants. In Sweden, with a population of approximately 9.4 million people, the overall prevalence of GD is approximately 1:170,000 inhabitants. Patients with type 1 GD (GD1) suffer from an increased susceptibility to malignancies, and while the underlying mechanisms are not known, it is postulated to be associated with macrophage dysfunction and immune dysregulation in GD. The pathophysiology of hyperferritinemia in GD has not yet been elucidated and different mechanisms are possible, including the chronic inflammation hypothesis. Soluble interleukin-2 receptor a (sIL-2Ra) is released from activated T and B cells, monocytes and some malignant cells. To the best of our knowledge, only one previous study examined sIL-2Ra levels in GD, and none has studied it in correlation with ferritinemia. Objectives: This study was undertaken to evaluate serum ferritin and sIL-2Ra levels in untreated GD1 patients at diagnosis. Patients and Methods: Between 2002 and 2012, 13 patients were diagnosed with GD1 in the Stockholm area. In all of them, the diagnosis of GD was confirmed by a low activity of b-glucosidase in peripheral blood leukocytes and an increased activity of plasma chitotriosidase. Further direct DNA sequencing revealed mutations in the GBA1 gene in all cases. Serum ferritin levels (ref.: 30–350 mg/L) were routinely measured on all GD1 patients at diagnosis. Iron overload was defined as hyperferritinemia >500 mg/L. Serum levels of sIL-2Ra (ref.: 321–565 U/mL) were measured by ELISA, using the quantitative 'sandwich' enzyme immunoassay, on the IMMULITE® 1000 Immunoassay System (Siemens Medical Solutions Diagnostics, Tarrytown, NY, USA). The files were reviewed for the collection of relevant clinical data. Results: Elevated serum ferritin >500 mg/L was present in all but 1 patient (92%). Interestingly, all ethnic Swedish patients (7 persons) had significantly higher ferritin levels (median 1910 mg/L; range 1108–4408) as compared to non-ethnic Swedish patients (median 900 mg/L; range 81–1238). The median age of the ethnic Swedish patients at diagnosis was 30 years (range 3– 61 years); 3 of them were splenectomized and two of them developed Parkinson's disease. The median age of the non-ethnic Swedish GD1 patien 3 of them were splenectomized and two of them developed Parkinson's disease. The median age of the non-ethnic Swedish GD1 patients at diagnosis was 53 years (range 3–60 years); only one of them with the most severe phenotype and heterozygous private GBA1 mutations was splenectomized in Iran at the age of 5 years. None of the nonethnic Swedish GD1 patients developed Parkinson's disease. The median value of serum sIL-2Ra was 373 U/mL (range 249– 774) and it was within normal range in 92% patients (12/13).
0001-5814/$ – see front matter
acta haematologica polonica 44s (2013) 180–181
181
Conclusions: The study revealed that iron overload is common in GD1 patients in Sweden. It is possible that ethnic Swedish patients experience a more severe GD phenotype and have a somewhat higher risk of developing Parkinson's disease. Notably, unlike hemophagocytic lymphohistiocytosis, hyperferritinemia in GD1 is not associated with high serum levels of sIL-2Ra, which mainly reflects T cell activation. Thus, our results rather support an immunosuppressive effect of hyperferritinemia, which is in line with the observed increased susceptibility to malignancies in GD1. http://dx.doi.org/10.1016/j.achaem.2013.07.186