Synthetic peptides mapping to epitopes of the extracellular domain of the interleukin-2 receptor β-chain to inhibit T-cell activation

2004 ◽  
Vol 36 (6) ◽  
pp. 1723-1727 ◽  
Author(s):  
T. Parissi ◽  
K. Chatzantoni ◽  
S. Deraos ◽  
I. Matsoukas ◽  
A. Mouzaki
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Synthetic Peptides ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Extracellular Domain ◽  
Interleukin 2 Receptor ◽  
Β Chain

Deregulated T cell activation and autoimmunity in mice lacking interleukin-2 receptor beta

Science ◽  
1995 ◽  
Vol 268 (5216) ◽  
pp. 1472-1476 ◽  
Author(s):  
H Suzuki ◽  
T. Kundig ◽  
C Furlonger ◽  
A Wakeham ◽  
E Timms ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Interleukin 2 Receptor ◽  
Receptor Beta

scholarly journals The Role of Soluble Interleukin-2 Receptor (sIL-2r) in Diagnosis of Adult Hemophagocytic Lymphohistiocytosis (HLH): A Single Center Retrospective Study

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 999-999
Author(s):  
Anna Hayden ◽  
Molly Lin ◽  
Sujin Park ◽  
Andre Mattman ◽  
Morris Pudek ◽  
...  
Keyword(s):  
Retrospective Study ◽  
T Cell ◽  
Disease Activity ◽  
T Cell Activation ◽  
Immune Activation ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Interleukin 2 Receptor ◽  
Soluble Interleukin 2 Receptor

Abstract Purpose: Serum soluble interleukin-2 receptor (sIL-2r) is considered an important disease marker in hemophagocytic lymphohistiocytosis (HLH). High levels of sIL2r are indicative of T-cell activation, and sIL2r > 2400 U/mL was 93% sensitive and 100% specific for pediatric HLH in the HLH-2004 diagnostic criteria. [1] There are no published data on its performance characteristics in adults and very limited data in children. [2] We conducted a retrospective study to examine the diagnostic sensitivity and specificity of sIL-2r in diagnosing HPS/HLH, to assess how it varies with disease severity, determine its prognostic significance and ability to discriminate between subgroups of HPS/HLH. Methods: Retrospective data was collected on adult patients with at least one sIL-2r level at Vancouver General Hospital in Vancouver, Canada between March 2012 and April 2017. Patients were subdivided into HLH and non-HLH groups. Sensitivity, specificity, prognosis associated with sIL-2r >10,000U/ml, utility as a marker of disease activity and mean sIL-2r between subgroups of HLH were evaluated. Non-HLH patients did not have convincing evidence to suggest HLH and did not receive HLH-specific therapy. Serum sIL-2r levels were enzyme-linked immunosorbent assay (ELISA; Siemens IMMULITE Immunoassay platform, adult reference range 241-846 U/ml). Results: 81 patients were included, 41 with HLH and 40 with an alternate diagnosis (non-HLH). Non-HLH diagnoses included sepsis, histiocyte disorders, multiple transfusions, liver disease, cardiac disease, autoimmune disease/vasculitis, and other inflammatory diseases. The sensitivity of sIL-2r >2400 U/ml was 93% (95% CI 0.79 - 0.98) and specificity 63% (95% CI 0.46 - 0.77). Specificity improved to 93% (95% CI 0.79 - 0.98) with a threshold of sIL-2r >10,000U/ml. Based on ROC curves, sIL2r is a good diagnostic test (AUC of 0.86) with a threshold that optimizes sensitivity and specificity of 2785U/ml and ferritin is a fair test (AUC 0.78) with an optimal threshold of 5775 ug/L. Similar to ferritin, sIL-2r levels correlated with disease activity in seven HLH patients that had multiple sIL-2r levels drawn during their disease course. Within the HLH group, sIL-2r >10,000U/ml was not associated with worse prognosis. Higher sIL-2r levels were seen in malignancy associated HLH (MAHS) as compared to infection associated HLH (IAHS) and macrophage activation syndrome (MAS). Conclusion: sIL-2r >2,400U/ml is a sensitive test for diagnosis of adult HPS/HLH and has utility in monitoring disease activity. At higher levels (sIL-2r >10,000U/ml), this biomarker loses sensitivity but gains specificity in diagnosing HPS/HLH. Higher sIL-2r levels may indicate MAHS when the underlying etiology is unclear. In adults, secondary HPS/HLH is much more common than primary HLH, and all patients in this study were presumed to be secondary. The defining features of secondary HPS/HLH are pathologic immune activation and hypercytokinemia leading to end organ damage. SIL-2r is elevated in numerous conditions associated with T-cell activation and inflammation, such as lymphoma and autoimmune lymphoproliferative syndrome (ALPS), and larger prospective studies of adults with these and other conditions are needed to better define the specificity of increased sIL-2r for HPS/HLH. Since adult secondary HPS/HLH is increasingly diagnosed and treated in many centers, diagnostic criteria for adult secondary HPS/HLH should incorporate markers of hypercytokinemia and immune activation. References: 1. Janka, G.E. and E.M. Schneider, Modern management of children with haemophagocytic lymphohistiocytosis. Br J Haematol, 2004. 124(1): p. 4-14. 2. Lin, M., et al., Clinical utility of soluble interleukin-2 receptor in hemophagocytic syndromes: a systematic scoping review. Ann Hematol, 2017. 96(8): p. 1241-1251. Disclosures No relevant conflicts of interest to declare.

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