CLINICAL SIGNIFICANCE OF SERUM HEME OXYGENASE 1 IN PATIENTS WITH SECONDARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS
(Abstract release date: 05/19/16)
EHA Library. Wang D. 06/09/16; 132722; E1173
Ms. Dongjiao Wang
Contributions
Contributions
Abstract
Abstract: E1173
Type: Eposter Presentation
Background
Hemophagocytic lymphohistiocytosis (HLH) is a rare, threatening-life clinical syndrome, caused by cytokines storm due to provoked, uncontrolled proliferation and over activation of lymphocytes and macrophages. sHLH in adults is an etiologically heterogeneous entity that has been associated with infections, autoimmune disorders, and haematological malignancies, mainly with non-hodgkin lymphoma. Clinically, these disorders feature fever, hepatosplenomegaly, severe cytopenias, activated macrophages in hematopoietic organs. Biochemical abnormalities include hypofibrinogenemia, hypertriglyceridemia, and increased levels of soluble interleukin-2 receptor (sCD25), serum ferritin(SF), and a large number of inflammatory other cytokines.Heme oxygenase 1 (HO-1) is an inducible stress-response enzyme and it is also an rate-limitting enzyme that degrades heme to biliverdin, carbon monoxide (CO) and free iron in mammalian cells. Biliverdin and CO gain particular interest because of mediating most of anti-inflammatory, antioxidant and anti-apoptotic effects of HO-1. HO-1 can be induced by various stressors such as oxidative stress, inflammatory cytokine, heavy metals and ultraviolet irradiation. HO-1 is constitutively expressed in peripheral monocytes and organ-localized macrophages such as hepatic kupffer cells and splenic macrophages. These facts suggest that HO-1 plays a key role in regulation of the inflammatory response in physiological and pathological conditions.Recently, there are accumulating evidences that increased serum HO-1 level is related to macrophage activation. Herein, we measured serum HO-1 levels in sHLH patients and analyzed the relationship of serum HO-1 with other biological markers of sHLH. The results show that serum HO-1 is a novel marker to evaluating severity and activity of sHLH. In addition, serum HO-1 may be an indicator using in differentiating autoimmune-associated hemophagocytic lymphohistiocytosis (AHLH) from other underline etiologies of sHLH.
Aims
To investigate the levels and clinical significance of heme oxygenase 1 (HO-1) in patients with secondary hemophagocytic lymphohistiocytosis (sHLH).
Methods
Serum HO-1 levels were determined by using enzyme linked immunosorbent assays (ELISA) in 43 sHLH patients and 12 healthy contrlols. Clinically relevant laboratory values, including white blood cell (WBC), hemoglobin (HB), platelet (PLT), serum ferritin (SF), albuminin (ALB), alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), fibrinogen (FIB), blood sedimentation rate (ESR), triglyceride (TG), soluble interleukin-2 receptor (sCD25) and C reactive protein (CRP) were collected.
Results
(1) Serum HO-1 levels of the newly diagnosed group were found to be significantly higher than that of the healthy control group (P =0.001). (2) Serum HO-1 levels of the newly diagnosed AHLH (autoimmune-associated HLH) were significantly higher than those in patients with IHLH (infection-associated HLH), LHLH (lymphoma-associated HLH) and healthy controls (P<0.05); (3) The serum HO-1 levels of the clinical remission group were significantly lower than that of the newly diagnosed group (P<0.05);(4) Serum HO-1 levels in newly diagnosed sHLH patients positively correlated with SF (r=0.582, P<0.001), and negatively with ALB (r=-0.308, P=0.045); (5) The receiver operating characteristic curves (ROC) for serum HO-1 levels of patients with sHLH and healthy controls produced a cutoff value at 520.4ng/mL, with its sensitivity and specificity being 90.7% and 100%, respectively. In addition, an optimal cutoff value for HO-1 was 2922.3ng/mL, and Its sensitivity and specificity were 100% and 99.2 %, in patients with AHLH and non-AHLH (LHLH+IHLH), separately. Another ROC for SF levels of patients with AHLH and non-AHLH(IHLH+LHLH) yielded an optimal cutoff value of 1189.0 ng/mL and its sensitivity and specificity were 85.7% and 55.5 %, respectively .
Conclusion
Serum HO-1 levels are clinically significant in disease diagnosis, differential diagnosis, evaluating disease activity and treatment outcomes in patients with sHLH.
Session topic: E-poster
Keyword(s): Bone marrow involvement, Cytokine, Phagocytes
Type: Eposter Presentation
Background
Hemophagocytic lymphohistiocytosis (HLH) is a rare, threatening-life clinical syndrome, caused by cytokines storm due to provoked, uncontrolled proliferation and over activation of lymphocytes and macrophages. sHLH in adults is an etiologically heterogeneous entity that has been associated with infections, autoimmune disorders, and haematological malignancies, mainly with non-hodgkin lymphoma. Clinically, these disorders feature fever, hepatosplenomegaly, severe cytopenias, activated macrophages in hematopoietic organs. Biochemical abnormalities include hypofibrinogenemia, hypertriglyceridemia, and increased levels of soluble interleukin-2 receptor (sCD25), serum ferritin(SF), and a large number of inflammatory other cytokines.Heme oxygenase 1 (HO-1) is an inducible stress-response enzyme and it is also an rate-limitting enzyme that degrades heme to biliverdin, carbon monoxide (CO) and free iron in mammalian cells. Biliverdin and CO gain particular interest because of mediating most of anti-inflammatory, antioxidant and anti-apoptotic effects of HO-1. HO-1 can be induced by various stressors such as oxidative stress, inflammatory cytokine, heavy metals and ultraviolet irradiation. HO-1 is constitutively expressed in peripheral monocytes and organ-localized macrophages such as hepatic kupffer cells and splenic macrophages. These facts suggest that HO-1 plays a key role in regulation of the inflammatory response in physiological and pathological conditions.Recently, there are accumulating evidences that increased serum HO-1 level is related to macrophage activation. Herein, we measured serum HO-1 levels in sHLH patients and analyzed the relationship of serum HO-1 with other biological markers of sHLH. The results show that serum HO-1 is a novel marker to evaluating severity and activity of sHLH. In addition, serum HO-1 may be an indicator using in differentiating autoimmune-associated hemophagocytic lymphohistiocytosis (AHLH) from other underline etiologies of sHLH.
Aims
To investigate the levels and clinical significance of heme oxygenase 1 (HO-1) in patients with secondary hemophagocytic lymphohistiocytosis (sHLH).
Methods
Serum HO-1 levels were determined by using enzyme linked immunosorbent assays (ELISA) in 43 sHLH patients and 12 healthy contrlols. Clinically relevant laboratory values, including white blood cell (WBC), hemoglobin (HB), platelet (PLT), serum ferritin (SF), albuminin (ALB), alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), fibrinogen (FIB), blood sedimentation rate (ESR), triglyceride (TG), soluble interleukin-2 receptor (sCD25) and C reactive protein (CRP) were collected.
Results
(1) Serum HO-1 levels of the newly diagnosed group were found to be significantly higher than that of the healthy control group (P =0.001). (2) Serum HO-1 levels of the newly diagnosed AHLH (autoimmune-associated HLH) were significantly higher than those in patients with IHLH (infection-associated HLH), LHLH (lymphoma-associated HLH) and healthy controls (P<0.05); (3) The serum HO-1 levels of the clinical remission group were significantly lower than that of the newly diagnosed group (P<0.05);(4) Serum HO-1 levels in newly diagnosed sHLH patients positively correlated with SF (r=0.582, P<0.001), and negatively with ALB (r=-0.308, P=0.045); (5) The receiver operating characteristic curves (ROC) for serum HO-1 levels of patients with sHLH and healthy controls produced a cutoff value at 520.4ng/mL, with its sensitivity and specificity being 90.7% and 100%, respectively. In addition, an optimal cutoff value for HO-1 was 2922.3ng/mL, and Its sensitivity and specificity were 100% and 99.2 %, in patients with AHLH and non-AHLH (LHLH+IHLH), separately. Another ROC for SF levels of patients with AHLH and non-AHLH(IHLH+LHLH) yielded an optimal cutoff value of 1189.0 ng/mL and its sensitivity and specificity were 85.7% and 55.5 %, respectively .
Conclusion
Serum HO-1 levels are clinically significant in disease diagnosis, differential diagnosis, evaluating disease activity and treatment outcomes in patients with sHLH.
Session topic: E-poster
Keyword(s): Bone marrow involvement, Cytokine, Phagocytes
Abstract: E1173
Type: Eposter Presentation
Background
Hemophagocytic lymphohistiocytosis (HLH) is a rare, threatening-life clinical syndrome, caused by cytokines storm due to provoked, uncontrolled proliferation and over activation of lymphocytes and macrophages. sHLH in adults is an etiologically heterogeneous entity that has been associated with infections, autoimmune disorders, and haematological malignancies, mainly with non-hodgkin lymphoma. Clinically, these disorders feature fever, hepatosplenomegaly, severe cytopenias, activated macrophages in hematopoietic organs. Biochemical abnormalities include hypofibrinogenemia, hypertriglyceridemia, and increased levels of soluble interleukin-2 receptor (sCD25), serum ferritin(SF), and a large number of inflammatory other cytokines.Heme oxygenase 1 (HO-1) is an inducible stress-response enzyme and it is also an rate-limitting enzyme that degrades heme to biliverdin, carbon monoxide (CO) and free iron in mammalian cells. Biliverdin and CO gain particular interest because of mediating most of anti-inflammatory, antioxidant and anti-apoptotic effects of HO-1. HO-1 can be induced by various stressors such as oxidative stress, inflammatory cytokine, heavy metals and ultraviolet irradiation. HO-1 is constitutively expressed in peripheral monocytes and organ-localized macrophages such as hepatic kupffer cells and splenic macrophages. These facts suggest that HO-1 plays a key role in regulation of the inflammatory response in physiological and pathological conditions.Recently, there are accumulating evidences that increased serum HO-1 level is related to macrophage activation. Herein, we measured serum HO-1 levels in sHLH patients and analyzed the relationship of serum HO-1 with other biological markers of sHLH. The results show that serum HO-1 is a novel marker to evaluating severity and activity of sHLH. In addition, serum HO-1 may be an indicator using in differentiating autoimmune-associated hemophagocytic lymphohistiocytosis (AHLH) from other underline etiologies of sHLH.
Aims
To investigate the levels and clinical significance of heme oxygenase 1 (HO-1) in patients with secondary hemophagocytic lymphohistiocytosis (sHLH).
Methods
Serum HO-1 levels were determined by using enzyme linked immunosorbent assays (ELISA) in 43 sHLH patients and 12 healthy contrlols. Clinically relevant laboratory values, including white blood cell (WBC), hemoglobin (HB), platelet (PLT), serum ferritin (SF), albuminin (ALB), alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), fibrinogen (FIB), blood sedimentation rate (ESR), triglyceride (TG), soluble interleukin-2 receptor (sCD25) and C reactive protein (CRP) were collected.
Results
(1) Serum HO-1 levels of the newly diagnosed group were found to be significantly higher than that of the healthy control group (P =0.001). (2) Serum HO-1 levels of the newly diagnosed AHLH (autoimmune-associated HLH) were significantly higher than those in patients with IHLH (infection-associated HLH), LHLH (lymphoma-associated HLH) and healthy controls (P<0.05); (3) The serum HO-1 levels of the clinical remission group were significantly lower than that of the newly diagnosed group (P<0.05);(4) Serum HO-1 levels in newly diagnosed sHLH patients positively correlated with SF (r=0.582, P<0.001), and negatively with ALB (r=-0.308, P=0.045); (5) The receiver operating characteristic curves (ROC) for serum HO-1 levels of patients with sHLH and healthy controls produced a cutoff value at 520.4ng/mL, with its sensitivity and specificity being 90.7% and 100%, respectively. In addition, an optimal cutoff value for HO-1 was 2922.3ng/mL, and Its sensitivity and specificity were 100% and 99.2 %, in patients with AHLH and non-AHLH (LHLH+IHLH), separately. Another ROC for SF levels of patients with AHLH and non-AHLH(IHLH+LHLH) yielded an optimal cutoff value of 1189.0 ng/mL and its sensitivity and specificity were 85.7% and 55.5 %, respectively .
Conclusion
Serum HO-1 levels are clinically significant in disease diagnosis, differential diagnosis, evaluating disease activity and treatment outcomes in patients with sHLH.
Session topic: E-poster
Keyword(s): Bone marrow involvement, Cytokine, Phagocytes
Type: Eposter Presentation
Background
Hemophagocytic lymphohistiocytosis (HLH) is a rare, threatening-life clinical syndrome, caused by cytokines storm due to provoked, uncontrolled proliferation and over activation of lymphocytes and macrophages. sHLH in adults is an etiologically heterogeneous entity that has been associated with infections, autoimmune disorders, and haematological malignancies, mainly with non-hodgkin lymphoma. Clinically, these disorders feature fever, hepatosplenomegaly, severe cytopenias, activated macrophages in hematopoietic organs. Biochemical abnormalities include hypofibrinogenemia, hypertriglyceridemia, and increased levels of soluble interleukin-2 receptor (sCD25), serum ferritin(SF), and a large number of inflammatory other cytokines.Heme oxygenase 1 (HO-1) is an inducible stress-response enzyme and it is also an rate-limitting enzyme that degrades heme to biliverdin, carbon monoxide (CO) and free iron in mammalian cells. Biliverdin and CO gain particular interest because of mediating most of anti-inflammatory, antioxidant and anti-apoptotic effects of HO-1. HO-1 can be induced by various stressors such as oxidative stress, inflammatory cytokine, heavy metals and ultraviolet irradiation. HO-1 is constitutively expressed in peripheral monocytes and organ-localized macrophages such as hepatic kupffer cells and splenic macrophages. These facts suggest that HO-1 plays a key role in regulation of the inflammatory response in physiological and pathological conditions.Recently, there are accumulating evidences that increased serum HO-1 level is related to macrophage activation. Herein, we measured serum HO-1 levels in sHLH patients and analyzed the relationship of serum HO-1 with other biological markers of sHLH. The results show that serum HO-1 is a novel marker to evaluating severity and activity of sHLH. In addition, serum HO-1 may be an indicator using in differentiating autoimmune-associated hemophagocytic lymphohistiocytosis (AHLH) from other underline etiologies of sHLH.
Aims
To investigate the levels and clinical significance of heme oxygenase 1 (HO-1) in patients with secondary hemophagocytic lymphohistiocytosis (sHLH).
Methods
Serum HO-1 levels were determined by using enzyme linked immunosorbent assays (ELISA) in 43 sHLH patients and 12 healthy contrlols. Clinically relevant laboratory values, including white blood cell (WBC), hemoglobin (HB), platelet (PLT), serum ferritin (SF), albuminin (ALB), alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), fibrinogen (FIB), blood sedimentation rate (ESR), triglyceride (TG), soluble interleukin-2 receptor (sCD25) and C reactive protein (CRP) were collected.
Results
(1) Serum HO-1 levels of the newly diagnosed group were found to be significantly higher than that of the healthy control group (P =0.001). (2) Serum HO-1 levels of the newly diagnosed AHLH (autoimmune-associated HLH) were significantly higher than those in patients with IHLH (infection-associated HLH), LHLH (lymphoma-associated HLH) and healthy controls (P<0.05); (3) The serum HO-1 levels of the clinical remission group were significantly lower than that of the newly diagnosed group (P<0.05);(4) Serum HO-1 levels in newly diagnosed sHLH patients positively correlated with SF (r=0.582, P<0.001), and negatively with ALB (r=-0.308, P=0.045); (5) The receiver operating characteristic curves (ROC) for serum HO-1 levels of patients with sHLH and healthy controls produced a cutoff value at 520.4ng/mL, with its sensitivity and specificity being 90.7% and 100%, respectively. In addition, an optimal cutoff value for HO-1 was 2922.3ng/mL, and Its sensitivity and specificity were 100% and 99.2 %, in patients with AHLH and non-AHLH (LHLH+IHLH), separately. Another ROC for SF levels of patients with AHLH and non-AHLH(IHLH+LHLH) yielded an optimal cutoff value of 1189.0 ng/mL and its sensitivity and specificity were 85.7% and 55.5 %, respectively .
Conclusion
Serum HO-1 levels are clinically significant in disease diagnosis, differential diagnosis, evaluating disease activity and treatment outcomes in patients with sHLH.
Session topic: E-poster
Keyword(s): Bone marrow involvement, Cytokine, Phagocytes
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