Hemophagocytic lymphohistiocytosis (HLH) is an often-life-threatening hyperinflammatory syndrome characterized by excessive immune cell activation and cytokine production, resulting in cytokine storm. If uncontrolled, HLH often leads to systemic inflammation, multi-organ failure and death. HLH is defined based on etiology as either familial (primary) or acquired (secondary). Familial HLH is caused by known germline mutations of cytolytic pathway genes essential for proper lymphocyte cytotoxic function. Acquired HLH, also referred to as macrophage activation syndrome (MAS), is associated with infections, malignancies, systemic juvenile idiopathic arthritis, and systemic lupus erythematosus. Despite their different causes, familial and acquired HLH have overlapping symptoms. According to the HLH-2004 protocol, a patient is diagnosed with HLH when fulfilling five of eight criteria (fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis, low/absent NK-cell-activity, hyperferritinemia, and high levels of soluble IL-2 receptor (CD25) levels).
Our understanding of HLH etiology, pathophysiology, and development of novel therapeutics have evolved thanks to past and current research on this topic. Despite it being a rare disease, deciphering the cellular and molecular mechanisms that lead to uncontrolled hyperinflammation has vast applications in a plethora of other immune pathologies. For example, HLH research has contributed to our understanding of multisystem inflammatory syndrome (MIS) associated with SARS-CoV-2 infection in this current COVID-19 pandemic and cytokine release syndrome (CRS) in response to CAR T cell therapies for the treatment of cancer. Despite their different etiologies, these pathologies share a common denominator factor which is the aberrant and uncontrolled immune response of the host. Therefore, better understanding of the pathophysiology of HLH would not only help us improve survival of HLH patients, which is currently around 60%, but would also help elucidate the mechanisms of other cytokine storm syndromes with overlapping pathology.
This research topic is focused on providing a more detailed overview towards a better understanding of hemophagocytic lymphohistiocytosis. We seek Original Research, Review, and Mini-review articles focusing on, but not limited to, the following areas:
• HLH etiology considering the current developments in our understanding of cytokine storm syndromes
• The role of immune cells in fueling hyperinflammation
• The effect of various cytokines in the cytokine storm
• Therapeutic strategies for the treatment of HLH, including current clinical trials and potential novel candidates
Our understanding of HLH etiology, pathophysiology, and development of novel therapeutics have evolved thanks to past and current research on this topic. Despite it being a rare disease, deciphering the cellular and molecular mechanisms that lead to uncontrolled hyperinflammation has vast applications in a plethora of other immune pathologies. For example, HLH research has contributed to our understanding of multisystem inflammatory syndrome (MIS) associated with SARS-CoV-2 infection in this current COVID-19 pandemic and cytokine release syndrome (CRS) in response to CAR T cell therapies for the treatment of cancer. Despite their different etiologies, these pathologies share a common denominator factor which is the aberrant and uncontrolled immune response of the host. Therefore, better understanding of the pathophysiology of HLH would not only help us improve survival of HLH patients, which is currently around 60%, but would also help elucidate the mechanisms of other cytokine storm syndromes with overlapping pathology.
This Research Topic is focused on providing a more detailed overview towards a better understanding of hemophagocytic lymphohistiocytosis. We seek Original Research, Review, and Mini-review articles focusing on, but not limited to, the following areas:
• HLH etiology considering the current developments in our understanding of cytokine storm syndromes
• The role of immune cells in fueling hyperinflammation
• The effect of various cytokines in the cytokine storm
• Therapeutic strategies for the treatment of HLH, including current clinical trials and potential novel candidates
Hemophagocytic lymphohistiocytosis (HLH) is an often-life-threatening hyperinflammatory syndrome characterized by excessive immune cell activation and cytokine production, resulting in cytokine storm. If uncontrolled, HLH often leads to systemic inflammation, multi-organ failure and death. HLH is defined based on etiology as either familial (primary) or acquired (secondary). Familial HLH is caused by known germline mutations of cytolytic pathway genes essential for proper lymphocyte cytotoxic function. Acquired HLH, also referred to as macrophage activation syndrome (MAS), is associated with infections, malignancies, systemic juvenile idiopathic arthritis, and systemic lupus erythematosus. Despite their different causes, familial and acquired HLH have overlapping symptoms. According to the HLH-2004 protocol, a patient is diagnosed with HLH when fulfilling five of eight criteria (fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis, low/absent NK-cell-activity, hyperferritinemia, and high levels of soluble IL-2 receptor (CD25) levels).
Our understanding of HLH etiology, pathophysiology, and development of novel therapeutics have evolved thanks to past and current research on this topic. Despite it being a rare disease, deciphering the cellular and molecular mechanisms that lead to uncontrolled hyperinflammation has vast applications in a plethora of other immune pathologies. For example, HLH research has contributed to our understanding of multisystem inflammatory syndrome (MIS) associated with SARS-CoV-2 infection in this current COVID-19 pandemic and cytokine release syndrome (CRS) in response to CAR T cell therapies for the treatment of cancer. Despite their different etiologies, these pathologies share a common denominator factor which is the aberrant and uncontrolled immune response of the host. Therefore, better understanding of the pathophysiology of HLH would not only help us improve survival of HLH patients, which is currently around 60%, but would also help elucidate the mechanisms of other cytokine storm syndromes with overlapping pathology.
This research topic is focused on providing a more detailed overview towards a better understanding of hemophagocytic lymphohistiocytosis. We seek Original Research, Review, and Mini-review articles focusing on, but not limited to, the following areas:
• HLH etiology considering the current developments in our understanding of cytokine storm syndromes
• The role of immune cells in fueling hyperinflammation
• The effect of various cytokines in the cytokine storm
• Therapeutic strategies for the treatment of HLH, including current clinical trials and potential novel candidates
Our understanding of HLH etiology, pathophysiology, and development of novel therapeutics have evolved thanks to past and current research on this topic. Despite it being a rare disease, deciphering the cellular and molecular mechanisms that lead to uncontrolled hyperinflammation has vast applications in a plethora of other immune pathologies. For example, HLH research has contributed to our understanding of multisystem inflammatory syndrome (MIS) associated with SARS-CoV-2 infection in this current COVID-19 pandemic and cytokine release syndrome (CRS) in response to CAR T cell therapies for the treatment of cancer. Despite their different etiologies, these pathologies share a common denominator factor which is the aberrant and uncontrolled immune response of the host. Therefore, better understanding of the pathophysiology of HLH would not only help us improve survival of HLH patients, which is currently around 60%, but would also help elucidate the mechanisms of other cytokine storm syndromes with overlapping pathology.
This Research Topic is focused on providing a more detailed overview towards a better understanding of hemophagocytic lymphohistiocytosis. We seek Original Research, Review, and Mini-review articles focusing on, but not limited to, the following areas:
• HLH etiology considering the current developments in our understanding of cytokine storm syndromes
• The role of immune cells in fueling hyperinflammation
• The effect of various cytokines in the cytokine storm
• Therapeutic strategies for the treatment of HLH, including current clinical trials and potential novel candidates
