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Alexei A. Grom - One of the best experts on this subject based on the ideXlab platform.
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Macrophage Activation Syndrome in Rheumatic Diseases
Textbook of Autoinflammation, 2019Co-Authors: Alexei A. Grom, Edward M. BehrensAbstract:Macrophage Activation Syndrome is a hemophagocytic Syndrome presenting as a complication of a rheumatic disease. Excessive Activation and expansion of T lymphocytes and macrophagic histiocytes in MAS leads to a cytokine storm and hyperinflammation associated with extreme hyperferritinemia, cytopenias, liver dysfunction and coagulopathy resembling disseminated intravascular coagulation. It is a life-threatening condition and may progress to multiple organ failure. High dose glucocorticoids and cyclosporine A are most commonly used to treat MAS. Anakinra and intravenous immunoglobulin may be effective in some patients. Etoposide should be considered in more severe cases. Treatments under investigation include strategies aimed at neutralization of IFN-γ and IL-18.
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Macrophage Activation Syndrome
Oxford Textbook of Rheumatology, 2013Co-Authors: Alexei A. Grom, Athimalaipet V RamananAbstract:Macrophage Activation Syndrome (MAS) is a life-threatening condition caused by excessive Activation and proliferation of T lymphocytes and haemophagocytic Macrophages. Although MAS has been reported in association with almost any rheumatic disease, it is by far most common in systemic juvenile idiopathic arthritis. Flares of the underlying disease or infection are most common triggers of MAS. The pathognomonic feature of MAS is typically found in bone marrow: numerous, well-differentiated macrophagic histiocytes phagocytosing normal haematopoietic elements. The expansion of these histiocytes leads to a massive systemic inflammatory reaction associated with three cardinal clinical features: severe cytopenias, liver dysfunction, and coagulopathy consistent with disseminated intravascular coagulation. Clinically, MAS is strikingly similar to the autosomal recessive disorders collectively known as familial haemophagocytic lymphohistiocytosis (FHLH). FHLH has been associated with various genetic defects affecting the cytolytic pathway. Cytolytic function is profoundly depressed in MAS patients as well, and this abnormality is caused by both genetic and acquired factors. Studies in animals suggest that uncontrolled expansion of activated CD8+ T lymphocytes secreting cytokines that activate Macrophages is central to the pathophysiology of haemophagocytic Syndromes. Consistent with this view, the combination of steroids and ciclosporin, an immunosuppressant that preferentially inhibits T lymphocytes, is an effective treatment for the majority of MAS patients. Patients in whom MAS remains active despite this treatment present a serious challenge and require more aggressive immunosuppression. However, in MAS triggered by infection, the optimal level of immunosuppression is difficult to determine. As a result, reported mortality rates reach 20%.
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Macrophage Activation Syndrome: advances towards understanding pathogenesis
Current opinion in rheumatology, 2010Co-Authors: Alexei A. Grom, Elizabeth D. MellinsAbstract:Purpose of review Macrophage Activation Syndrome (MAS), a major cause of morbidity and mortality in pediatric rheumatology, is most strongly associated with systemic juvenile idiopathic arthritis (SJIA). There are no validated diagnostic criteria and early diagnosis is difficult. This review summarizes the progress in understanding of MAS pathophysiology that may help define specific diagnostic biomarkers.
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Macrophage Activation Syndrome in patients with systemic juvenile idiopathic arthritis is associated with MUNC13-4 polymorphisms.
Arthritis and rheumatism, 2008Co-Authors: Kejian Zhang, Jennifer Biroschak, David N. Glass, Susan D. Thompson, Terri H. Finkel, Murray H. Passo, Bryce A. Binstadt, Alexandra H. Filipovich, Alexei A. GromAbstract:Systemic juvenile idiopathic arthritis (JIA) is associated with Macrophage Activation Syndrome. Macrophage Activation Syndrome bears a close resemblance to familial hemophagocytic lymphohistiocytosis (HLH). The development of familial HLH has been recently associated with mutations in MUNC13-4. The purpose of this study was to assess for possible sequence alterations in MUNC13-4 in patients with systemic JIA/Macrophage Activation Syndrome. The MUNC13-4 sequence was analyzed in 18 unrelated patients with systemic JIA/Macrophage Activation Syndrome, using 32 primer pair sets designed to amplify the 32 exons and at least 100 basepairs of the adjacent intronic regions. DNA samples obtained from 73 unrelated patients with systemic JIA and no history of Macrophage Activation Syndrome and 229 unrelated healthy individuals were used as controls. The biallelic sequence variants in MUNC13-4 reported in familial HLH were present in 2 of the 18 patients with JIA/Macrophage Activation Syndrome. Further analysis of the MUNC13-4 sequences revealed an identical combination of 12 single-nucleotide polymorphisms (SNPs) in 9 of the remaining 16 patients with systemic JIA/Macrophage Activation Syndrome (56%). Additional analysis suggested that these 12 SNPs (154[-19] g>a, 261[+26] c>g, 388[+81] g>a, 388[+122] c>t, 570[-60] t>g, 888 G>C, 1389[+36] g>a, 1992[+5] g>a, 2447[+144] c>t, 2599 A>G, 2830[+37] c>g, 3198 A>G) were inherited as an extended haplotype. In several patients, in addition to the described haplotype, there were other SNPs in the second allele of MUNC13-4. Moreover, 1 patient had a complex mutation with 2 changes, 2542 A>C and 2943 G>C, in a cis configuration. The haplotype was present in only 27 (12%) of 229 healthy control subjects (chi(2) = 23.5) and in 6 (8.2%) of 73 patients with systemic JIA and no history of Macrophage Activation Syndrome. The data suggest an association between MUNC13-4 polymorphisms and Macrophage Activation Syndrome in patients with systemic JIA.
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Macrophage Activation Syndrome and reactive hemophagocytic lymphohistiocytosis: the same entities?
Current opinion in rheumatology, 2003Co-Authors: Alexei A. GromAbstract:Purpose of the review One of the most perplexing features of systemic-onset juvenile rheumatoid arthritis is the association with Macrophage Activation Syndrome, a life-threatening complication caused by excessive Activation and proliferation of T cells and Macrophages. The main purpose of the review is to summarize current understanding of the relation between Macrophage Activation Syndrome and other clinically similar hemophagocytic disorders. Recent findings Clinically, Macrophage Activation Syndrome has strong similarities with familial and virus-associated reactive hemophagocytic lymphohistiocytosis. The better understood familial hemophagocytic lymphohistiocytosis is a constellation of rare, autosomal recessive immune disorders. The most consistent immunologic abnormalities in patients with familial hemophagocytic lymphohistiocytosis are decreased natural killer and cytotoxic cell functions. In approximately one third of familial hemophagocytic lymphohistiocytosis patients, these immunologic abnormalities are secondary to mutations in the gene encoding perforin, a protein that mediates cytotoxic activity of natural killer and cytotoxic CD8 + T cells. Several recent studies have suggested that profoundly depressed natural killer cell activity and abnormal levels of perforin expression may be a feature of Macrophage Activation Syndrome in systemic-onset juvenile rheumatoid arthritis as well. Although it has been proposed that in both hemophagocytic lymphohistiocytosis and Macrophage Activation Syndrome, natural killer and cytotoxic cell dysfunction may lead to inadequate control of cellular immune responses, the exact nature of such dysregulation and the relation between Macrophage Activation Syndrome and hemophagocytic lymphohistiocytosis still remain to be determined.
Angelo Ravelli - One of the best experts on this subject based on the ideXlab platform.
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Macrophage Activation Syndrome in pediatrics.
Pediatric Allergy and Immunology, 2020Co-Authors: Alessandra Alongi, Roberta Naddei, Laura De Miglio, Valentina Natoli, Angelo RavelliAbstract:Macrophage Activation Syndrome (MAS) is a serious, potentially life-threatening, hyperinflammatory condition, which belongs to the spectrum of hemophagocytic lymphohistiocytosis (HLH) and can complicate several immunologic and rheumatic disorders. MAS is characterized by a dysfunctional immune response that is similar to that seen in other forms of HLH. Because MAS may pursue a rapidly fatal course, prompt recognition of its clinical and laboratory features and immediate therapeutic intervention are fundamental. Recently, a set of classification criteria for MAS complicating sJIA has been developed through a multinational collaborative effort. High-dose parenteral corticosteroids remain the mainstay of treatment of MAS.
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Macrophage Activation Syndrome
Hematology oncology clinics of North America, 2015Co-Authors: Angelo Ravelli, Sergio Davì, Francesca Minoia, Alberto Martini, Randy Q. CronAbstract:Macrophage Activation Syndrome (MAS) is a potentially life-threatening complication of rheumatic disorders that occurs most commonly in systemic juvenile idiopathic arthritis. In recent years, there have been several advances in the understanding of the pathophysiology of MAS. Furthermore, new classification criteria have been developed. Although the place of cytokine blockers in the management of MAS is still unclear, interleukin-1 inhibitors represent a promising adjunctive therapy, particularly in refractory cases.
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Macrophage Activation Syndrome
Indian Journal of Rheumatology, 2012Co-Authors: Bianca Lattanzi, Sergio Davì, Alberto Martini, Silvia Rosina, Nicoletta Solari, Stefano Lanni, Giulia Bracciolini, Angelo RavelliAbstract:Abstract Macrophage Activation Syndrome (MAS) is a serious, potentially life-threatening complication of rheumatic disorders, which is seen most commonly in systemic juvenile idiopathic arthritis (sJIA). It is characterised clinically by unremitting high fever, pancytopaenia, hepatosplenomegaly, hepatic dysfunction, encephalopathy, coagulation abnormalities and sharply increased levels of ferritin. The pathognomonic feature of the Syndrome is seen on bone marrow examination, which frequently, though not always, reveals numerous morphologically benign Macrophages exhibiting haemophagocytic activity. Macrophage Activation Syndrome is overt in 10% of children with sJIA but occurs subclinically in another 30–40%. Because MAS can follow a rapidly fatal course, prompt recognition of its clinical and laboratory features and immediate therapeutic intervention are essential. However, it is difficult to distinguish sJIA disease flare, infectious complications or medication side effects from MAS. A multinational collaborative effort aimed to develop diagnostic criteria for MAS in sJIA is under way. Although, the pathogenesis of MAS is unclear, the hallmark of the Syndrome is an uncontrolled Activation and proliferation of T lymphocytes and Macrophages, leading to massive hypersecretion of pro-inflammatory cytokines. Mutations in cytolytic pathway genes are increasingly being recognised in children who develop MAS as part of sJIA. Recently, a mouse model of MAS dependent on repeated stimulation through toll-like receptors was developed. The first-line therapy of MAS complicating sJIA is based on the parenteral administration of high doses of corticosteroids, with or without cyclosporine A. There is increasing evidence that biological therapies, particularly interleukin-1 inhibitors, represent a valuable adjunct to corticosteroids and cyclosporine A in treating MAS complicating sJIA.
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Macrophage Activation Syndrome in Childhood Rheumatic Diseases
Current Rheumatology Reviews, 2007Co-Authors: Angelo Ravelli, Alejandra Beatriz Pringe, Clara Malattia, I Sala, Alberto MartiniAbstract:Macrophage Activation Syndrome (MAS) is a life-threatening complication of systemic inflammatory disorders that is thought to be caused by the Activation and uncontrolled proliferation of T lymphocytes and Macrophages, leading to widespread hemophagocytosis and cytokine overproduction. Recent findings in hemophagocytic lymphohistiocytosis, a disease that is clinically very similar to MAS, highlight the possible pathogenetic role of a defective function of cytotoxic lymphocytes. Prompt diagnosis is important and recently preliminary diagnostic guidelines for the Syndrome have been proposed. The recognition that MAS belongs to the secondary or reactive hemophagocytic Syndromes has led to propose to rename it according to the contemporary classification of histiocytic disorders. Cyclosporine A has been found to be effective in patients with corticosteroid resistant MAS.
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Macrophage Activation Syndrome in juvenile systemic lupus erythematosus: an under-recognized complication?
Lupus, 2007Co-Authors: Alejandra Beatriz Pringe, Nicolino Ruperto, Alberto Martini, L Trail, Antonella Buoncompagni, Anna Loy, Luciana Breda, Angelo RavelliAbstract:Macrophage Activation Syndrome (MAS) is a life-threatening complication of rheumatic diseases that is thought to be caused by the Activation and uncontrolled proliferation of T lymphocytes and macr...
David D Sherry - One of the best experts on this subject based on the ideXlab platform.
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the diagnostic significance of soluble cd163 and soluble interleukin 2 receptor alpha chain in Macrophage Activation Syndrome and untreated new onset systemic juvenile idiopathic arthritis
Arthritis & Rheumatism, 2007Co-Authors: Jack H Bleesing, Anne Prada, David M Siegel, Joyce Villanueva, Judyann C Olson, Norman T Ilowite, Hermine I Brunner, Thomas A Griffin, Thomas B Graham, David D SherryAbstract:Objective Macrophage Activation Syndrome is characterized by an overwhelming inflammatory reaction driven by excessive expansion of T cells and hemophagocytic Macrophages. Levels of soluble interleukin-2 receptor alpha (sIL-2Ralpha) and soluble CD163 (sCD163) may reflect the degree of Activation and expansion of T cells and Macrophages, respectively. This study was undertaken to assess the value of serum sIL-2Ralpha and sCD163 in diagnosing acute Macrophage Activation Syndrome complicating systemic juvenile idiopathic arthritis (JIA). Methods Enzyme-linked immunosorbent assay was used to assess sIL-2Ralpha and sCD163 levels in sera from 7 patients with acute Macrophage Activation Syndrome complicating systemic JIA and 16 patients with untreated new-onset systemic JIA. The results were correlated with clinical features of established Macrophage Activation Syndrome, including ferritin levels. Results The median level of sIL-2Ralpha in the patients with Macrophage Activation Syndrome was 19,646 pg/ml (interquartile range [IQR] 18,128), compared with 3,787 pg/ml (IQR 3,762) in patients with systemic JIA (P = 0.003). Similarly, the median level of sCD163 in patients with Macrophage Activation Syndrome was 23,000 ng/ml (IQR 14,191), compared with 5,480 ng/ml (IQR 2,635) in patients with systemic JIA (P = 0.017). In 5 of 16 patients with systemic JIA, serum levels of sIL-2Ralpha or sCD163 were comparable with those in patients with acute Macrophage Activation Syndrome. These patients had high inflammatory activity associated with a trend toward lower hemoglobin levels (P = 0.11), lower platelet counts, and significantly higher ferritin levels (P = 0.02). Two of these 5 patients developed overt Macrophage Activation Syndrome several months later. Conclusion Levels of sIL-2Ralpha and sCD163 are promising diagnostic markers for Macrophage Activation Syndrome. They may also help identify patients with subclinical Macrophage Activation Syndrome.
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The diagnostic significance of soluble CD163 and soluble interleukin-2 receptor alpha-chain in Macrophage Activation Syndrome and untreated new-onset systemic juvenile idiopathic arthritis.
Arthritis and rheumatism, 2007Co-Authors: Jack H Bleesing, David M Siegel, Joyce Villanueva, Judyann C Olson, Norman T Ilowite, Hermine I Brunner, Thomas A Griffin, Thomas B Graham, Anne Leahy Prada, David D SherryAbstract:Macrophage Activation Syndrome is characterized by an overwhelming inflammatory reaction driven by excessive expansion of T cells and hemophagocytic Macrophages. Levels of soluble interleukin-2 receptor alpha (sIL-2Ralpha) and soluble CD163 (sCD163) may reflect the degree of Activation and expansion of T cells and Macrophages, respectively. This study was undertaken to assess the value of serum sIL-2Ralpha and sCD163 in diagnosing acute Macrophage Activation Syndrome complicating systemic juvenile idiopathic arthritis (JIA). Enzyme-linked immunosorbent assay was used to assess sIL-2Ralpha and sCD163 levels in sera from 7 patients with acute Macrophage Activation Syndrome complicating systemic JIA and 16 patients with untreated new-onset systemic JIA. The results were correlated with clinical features of established Macrophage Activation Syndrome, including ferritin levels. The median level of sIL-2Ralpha in the patients with Macrophage Activation Syndrome was 19,646 pg/ml (interquartile range [IQR] 18,128), compared with 3,787 pg/ml (IQR 3,762) in patients with systemic JIA (P = 0.003). Similarly, the median level of sCD163 in patients with Macrophage Activation Syndrome was 23,000 ng/ml (IQR 14,191), compared with 5,480 ng/ml (IQR 2,635) in patients with systemic JIA (P = 0.017). In 5 of 16 patients with systemic JIA, serum levels of sIL-2Ralpha or sCD163 were comparable with those in patients with acute Macrophage Activation Syndrome. These patients had high inflammatory activity associated with a trend toward lower hemoglobin levels (P = 0.11), lower platelet counts, and significantly higher ferritin levels (P = 0.02). Two of these 5 patients developed overt Macrophage Activation Syndrome several months later. Levels of sIL-2Ralpha and sCD163 are promising diagnostic markers for Macrophage Activation Syndrome. They may also help identify patients with subclinical Macrophage Activation Syndrome.
Alberto Martini - One of the best experts on this subject based on the ideXlab platform.
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Macrophage Activation Syndrome
Hematology oncology clinics of North America, 2015Co-Authors: Angelo Ravelli, Sergio Davì, Francesca Minoia, Alberto Martini, Randy Q. CronAbstract:Macrophage Activation Syndrome (MAS) is a potentially life-threatening complication of rheumatic disorders that occurs most commonly in systemic juvenile idiopathic arthritis. In recent years, there have been several advances in the understanding of the pathophysiology of MAS. Furthermore, new classification criteria have been developed. Although the place of cytokine blockers in the management of MAS is still unclear, interleukin-1 inhibitors represent a promising adjunctive therapy, particularly in refractory cases.
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Macrophage Activation Syndrome
Indian Journal of Rheumatology, 2012Co-Authors: Bianca Lattanzi, Sergio Davì, Alberto Martini, Silvia Rosina, Nicoletta Solari, Stefano Lanni, Giulia Bracciolini, Angelo RavelliAbstract:Abstract Macrophage Activation Syndrome (MAS) is a serious, potentially life-threatening complication of rheumatic disorders, which is seen most commonly in systemic juvenile idiopathic arthritis (sJIA). It is characterised clinically by unremitting high fever, pancytopaenia, hepatosplenomegaly, hepatic dysfunction, encephalopathy, coagulation abnormalities and sharply increased levels of ferritin. The pathognomonic feature of the Syndrome is seen on bone marrow examination, which frequently, though not always, reveals numerous morphologically benign Macrophages exhibiting haemophagocytic activity. Macrophage Activation Syndrome is overt in 10% of children with sJIA but occurs subclinically in another 30–40%. Because MAS can follow a rapidly fatal course, prompt recognition of its clinical and laboratory features and immediate therapeutic intervention are essential. However, it is difficult to distinguish sJIA disease flare, infectious complications or medication side effects from MAS. A multinational collaborative effort aimed to develop diagnostic criteria for MAS in sJIA is under way. Although, the pathogenesis of MAS is unclear, the hallmark of the Syndrome is an uncontrolled Activation and proliferation of T lymphocytes and Macrophages, leading to massive hypersecretion of pro-inflammatory cytokines. Mutations in cytolytic pathway genes are increasingly being recognised in children who develop MAS as part of sJIA. Recently, a mouse model of MAS dependent on repeated stimulation through toll-like receptors was developed. The first-line therapy of MAS complicating sJIA is based on the parenteral administration of high doses of corticosteroids, with or without cyclosporine A. There is increasing evidence that biological therapies, particularly interleukin-1 inhibitors, represent a valuable adjunct to corticosteroids and cyclosporine A in treating MAS complicating sJIA.
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Macrophage Activation Syndrome in Childhood Rheumatic Diseases
Current Rheumatology Reviews, 2007Co-Authors: Angelo Ravelli, Alejandra Beatriz Pringe, Clara Malattia, I Sala, Alberto MartiniAbstract:Macrophage Activation Syndrome (MAS) is a life-threatening complication of systemic inflammatory disorders that is thought to be caused by the Activation and uncontrolled proliferation of T lymphocytes and Macrophages, leading to widespread hemophagocytosis and cytokine overproduction. Recent findings in hemophagocytic lymphohistiocytosis, a disease that is clinically very similar to MAS, highlight the possible pathogenetic role of a defective function of cytotoxic lymphocytes. Prompt diagnosis is important and recently preliminary diagnostic guidelines for the Syndrome have been proposed. The recognition that MAS belongs to the secondary or reactive hemophagocytic Syndromes has led to propose to rename it according to the contemporary classification of histiocytic disorders. Cyclosporine A has been found to be effective in patients with corticosteroid resistant MAS.
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Macrophage Activation Syndrome in juvenile systemic lupus erythematosus: an under-recognized complication?
Lupus, 2007Co-Authors: Alejandra Beatriz Pringe, Nicolino Ruperto, Alberto Martini, L Trail, Antonella Buoncompagni, Anna Loy, Luciana Breda, Angelo RavelliAbstract:Macrophage Activation Syndrome (MAS) is a life-threatening complication of rheumatic diseases that is thought to be caused by the Activation and uncontrolled proliferation of T lymphocytes and macr...
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Chapter 4 Macrophage Activation Syndrome
Handbook of Systemic Autoimmune Diseases, 2007Co-Authors: Angelo Ravelli, Alberto MartiniAbstract:Publisher Summary This chapter provides an overview of the clinical features, epidemiology, nomenclature, pathogenesis, diagnosis, and management of Macrophage Activation Syndrome (MAS). MAS is a life-threatening complication of systemic inflammatory disorders seen most commonly in systemic juvenile idiopathic arthritis and is caused by the Activation and uncontrolled proliferation of T lymphocytes and Macrophages, leading to widespread hemophagocytosis and cytokine overproduction. The clinical presentation of MAS is generally acute and occasionally dramatic. Recent findings in hemophagocytic lymphohistiocytosis, a disease that is clinically very similar to MAS, highlight the possible pathogenetic role of a defective function of cytotoxic lymphocytes. Prompt diagnosis is important. The chapter outlines the preliminary diagnostic guidelines for the Syndrome are proposed. Cyclosporine A is effective in patients with corticosteroid resistant MAS, however, it is still unclear whether biologic agents have a role in the treatment of MAS.
Jack H Bleesing - One of the best experts on this subject based on the ideXlab platform.
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the diagnostic significance of soluble cd163 and soluble interleukin 2 receptor alpha chain in Macrophage Activation Syndrome and untreated new onset systemic juvenile idiopathic arthritis
Arthritis & Rheumatism, 2007Co-Authors: Jack H Bleesing, Anne Prada, David M Siegel, Joyce Villanueva, Judyann C Olson, Norman T Ilowite, Hermine I Brunner, Thomas A Griffin, Thomas B Graham, David D SherryAbstract:Objective Macrophage Activation Syndrome is characterized by an overwhelming inflammatory reaction driven by excessive expansion of T cells and hemophagocytic Macrophages. Levels of soluble interleukin-2 receptor alpha (sIL-2Ralpha) and soluble CD163 (sCD163) may reflect the degree of Activation and expansion of T cells and Macrophages, respectively. This study was undertaken to assess the value of serum sIL-2Ralpha and sCD163 in diagnosing acute Macrophage Activation Syndrome complicating systemic juvenile idiopathic arthritis (JIA). Methods Enzyme-linked immunosorbent assay was used to assess sIL-2Ralpha and sCD163 levels in sera from 7 patients with acute Macrophage Activation Syndrome complicating systemic JIA and 16 patients with untreated new-onset systemic JIA. The results were correlated with clinical features of established Macrophage Activation Syndrome, including ferritin levels. Results The median level of sIL-2Ralpha in the patients with Macrophage Activation Syndrome was 19,646 pg/ml (interquartile range [IQR] 18,128), compared with 3,787 pg/ml (IQR 3,762) in patients with systemic JIA (P = 0.003). Similarly, the median level of sCD163 in patients with Macrophage Activation Syndrome was 23,000 ng/ml (IQR 14,191), compared with 5,480 ng/ml (IQR 2,635) in patients with systemic JIA (P = 0.017). In 5 of 16 patients with systemic JIA, serum levels of sIL-2Ralpha or sCD163 were comparable with those in patients with acute Macrophage Activation Syndrome. These patients had high inflammatory activity associated with a trend toward lower hemoglobin levels (P = 0.11), lower platelet counts, and significantly higher ferritin levels (P = 0.02). Two of these 5 patients developed overt Macrophage Activation Syndrome several months later. Conclusion Levels of sIL-2Ralpha and sCD163 are promising diagnostic markers for Macrophage Activation Syndrome. They may also help identify patients with subclinical Macrophage Activation Syndrome.
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The diagnostic significance of soluble CD163 and soluble interleukin-2 receptor alpha-chain in Macrophage Activation Syndrome and untreated new-onset systemic juvenile idiopathic arthritis.
Arthritis and rheumatism, 2007Co-Authors: Jack H Bleesing, David M Siegel, Joyce Villanueva, Judyann C Olson, Norman T Ilowite, Hermine I Brunner, Thomas A Griffin, Thomas B Graham, Anne Leahy Prada, David D SherryAbstract:Macrophage Activation Syndrome is characterized by an overwhelming inflammatory reaction driven by excessive expansion of T cells and hemophagocytic Macrophages. Levels of soluble interleukin-2 receptor alpha (sIL-2Ralpha) and soluble CD163 (sCD163) may reflect the degree of Activation and expansion of T cells and Macrophages, respectively. This study was undertaken to assess the value of serum sIL-2Ralpha and sCD163 in diagnosing acute Macrophage Activation Syndrome complicating systemic juvenile idiopathic arthritis (JIA). Enzyme-linked immunosorbent assay was used to assess sIL-2Ralpha and sCD163 levels in sera from 7 patients with acute Macrophage Activation Syndrome complicating systemic JIA and 16 patients with untreated new-onset systemic JIA. The results were correlated with clinical features of established Macrophage Activation Syndrome, including ferritin levels. The median level of sIL-2Ralpha in the patients with Macrophage Activation Syndrome was 19,646 pg/ml (interquartile range [IQR] 18,128), compared with 3,787 pg/ml (IQR 3,762) in patients with systemic JIA (P = 0.003). Similarly, the median level of sCD163 in patients with Macrophage Activation Syndrome was 23,000 ng/ml (IQR 14,191), compared with 5,480 ng/ml (IQR 2,635) in patients with systemic JIA (P = 0.017). In 5 of 16 patients with systemic JIA, serum levels of sIL-2Ralpha or sCD163 were comparable with those in patients with acute Macrophage Activation Syndrome. These patients had high inflammatory activity associated with a trend toward lower hemoglobin levels (P = 0.11), lower platelet counts, and significantly higher ferritin levels (P = 0.02). Two of these 5 patients developed overt Macrophage Activation Syndrome several months later. Levels of sIL-2Ralpha and sCD163 are promising diagnostic markers for Macrophage Activation Syndrome. They may also help identify patients with subclinical Macrophage Activation Syndrome.
