Hemophagocytic syndromes — An update

Janka, Gritta; Lehmberg, Kai

doi:10.1016/j.blre.2014.03.002

Cited by 400 publications

(373 citation statements)

References 103 publications

Supporting

Mentioning

335

Contrasting

Unclassified

Order By: Relevance

“…The underlying pathomechanisms are pathological macrophage activation, functional natural killer (NK) cell defects, and polyclonal or oligoclonal lymphoproliferation. These dysfunctions may arise as complications of certain infections, oncologic treatments including hematopoietic stem cell transplantation (often referred to as infection-associated macrophage-activation syndrome or secondary hemophagocytic lymphohistiocytosis 67 or lymphoproliferative syndrome [with unknown genetic predisposition]), or as a main symptom of PIDs that stem from monogenetic communication defects between B and T cells. The manifestation of lymphoproliferative disorders is often triggered by primary EpsteinBarr virus (EBV) infection and is associated with a lack of invariant T-cell receptor NKT (iNKT) cells (eg, X-linked lymphoproliferative syndrome, CD27 deficiency, and interleukin-2 (IL-2)-inducible kinase deficiency).…”

Section: Immune Dysregulation Underlying Cytopenia In Pidmentioning

confidence: 99%

Autoimmune and other cytopenias in primary immunodeficiencies: pathomechanisms, novel differential diagnoses, and treatment

Seidel

2014

Blood

128

140

View full text Add to dashboard Cite

Autoimmunity and immune dysregulation may lead to cytopenia and represent key features of many primary immunodeficiencies (PIDs). Especially when cytopenia is the initial symptom of a PID, the order and depth of diagnostic steps have to be performed in accordance with both an immunologic and a hematologic approach and will help exclude disorders such as systemic lupus erythematosus, common variable immunodeficiency, and autoimmune lymphoproliferative syndromes, hemophagocytic disorders, lymphoproliferative diseases, and novel differential diagnoses such as MonoMac syndrome (GATA2 deficiency), CD27 deficiency, lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency, activated PI3KD syndrome (APDS), X-linked immunodeficiency with magnesium defect (MAGT1 deficiency), and others. Immunosuppressive treatment often needs to be initiated urgently, which impedes further relevant immunologic laboratory analyses aimed at defining the underlying PID. Awareness of potentially involved disease spectra ranging from hematologic to rheumatologic and immunologic disorders is crucial for identifying a certain proportion of PID phenotypes and genotypes among descriptive diagnoses such as autoimmune hemolytic anemia, chronic immune thrombocytopenia, Evans syndrome, severe aplastic anemia/refractory cytopenia, and others. A synopsis of pathomechanisms, novel differential diagnoses, and advances in treatment options for cytopenias in PID is provided to facilitate multidisciplinary management and to bridge different approaches.

show abstract

Section: Immune Dysregulation Underlying Cytopenia In Pidmentioning

confidence: 99%

Autoimmune and other cytopenias in primary immunodeficiencies: pathomechanisms, novel differential diagnoses, and treatment

Seidel

2014

Blood

128

140

View full text Add to dashboard Cite

show abstract

“…One potential player in the pathogenic process of HLH might be regulatory T (Treg) cells. 9 Treg cells have a unique suppressive function in the immune system, a function imparted by the transcription factor forkhead box protein P3 (Foxp3). Mutations in FOXP3 cause a fatal autoimmune and inflammatory disorder in both human subjects (immune dysregulation, polyendocrinopathy, enteropathy, X-linked [IPEX] syndrome) and mice (Scurfy mice).…”

mentioning

confidence: 99%

IL-2 consumption by highly activated CD8 T cells induces regulatory T-cell dysfunction in patients with hemophagocytic lymphohistiocytosis

Humblet-Baron

Franckaert

Dooley

et al. 2016

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

Background: Hemophagocytic lymphohistiocytosis (HLH) is a severe inflammatory condition driven by excessive CD8 1 T-cell activation. HLH occurs as both acquired and familial hemophagocytic lymphohistiocytosis (FHL) forms. In both conditions, a sterile or infectious trigger is required for disease initiation, which then becomes self-sustaining and lifethreatening. Recent studies have attributed the key distal event to excessive IFN-g production; however, the proximal events driving immune dysregulation have remained undefined. Objective: We sought to investigate the role of regulatory T (Treg) cells in the pathophysiology of experimental FHL. Methods: Because mutation in perforin is a common cause of FHL, we used an experimental FHL mouse model in which disease in perforin-deficient mice is triggered by lymphocytic choriomeningitis virus (LCMV). We assessed Treg and CD8 1 T-cell homeostasis and activation during the changing systemic conditions in the mice. In addition, human blood samples were collected and analyzed during the HLH episode. Results: We found no primary Treg cell defects in perforindeficient mice. However, Treg cell numbers collapsed after LCMV inoculation. The collapse of Treg cell numbers in LCMV-triggered perforin-deficient, but not wild-type, mice was accompanied by the combination of lower IL-2 secretion by conventional CD4 1 T cells, increased IL-2 consumption by activated CD8 1 T cells, and secretion of competitive soluble CD25. Moreover low Treg cell numbers were observed in untreated patients experiencing HLH flares. Conclusion: These results demonstrate that excessive CD8 1 T-cell activation rewires the IL-2 homeostatic network away

show abstract

“…MAS is a life-threatening complication defined by overwhelming inflammation, which results in a constellation of symptoms and objective findings deriving from aberrant activation and expansion of T lymphocytes and hemophagocytic macrophages, displaying persistent unremitting fever, cytopenia, multiorgan dysfunction, hyperferritinemia, hypertriglyceridemia, and high-soluble interleukin-2 (IL-2) receptor levels (2). This severe picture occurs secondarily in several underlying conditions, such as autoimmune diseases, infections, T cell lymphoproliferative disorders, granulomatous disorders, metabolic diseases, and hereditary immune deficiencies with hypopigmentation.…”

Section: To the Editormentioning

confidence: 99%

Outburst of Macrophage Activation Syndrome in Mevalonate Kinase Deficiency: Comment on the Article by Schulert et al

Rigante

2015

Arthritis Care & Research

View full text Add to dashboard Cite

Hemophagocytic syndromes — An update

Cited by 400 publications

References 103 publications

Autoimmune and other cytopenias in primary immunodeficiencies: pathomechanisms, novel differential diagnoses, and treatment

Autoimmune and other cytopenias in primary immunodeficiencies: pathomechanisms, novel differential diagnoses, and treatment

IL-2 consumption by highly activated CD8 T cells induces regulatory T-cell dysfunction in patients with hemophagocytic lymphohistiocytosis

Outburst of Macrophage Activation Syndrome in Mevalonate Kinase Deficiency: Comment on the Article by Schulert et al

Contact Info

Product

Resources

About