Soluble hemoglobin–haptoglobin scavenger receptor CD163 as a lineage‐specific marker in the reactive hemophagocytic syndrome

Abstract

Reactive hemophagocytic syndrome (RHS) is a disease of overwhelming macrophage activity triggered by infection, malignancy or autoimmune disorders. Currently used laboratory markers for the quantitative assessment of monocyte/macrophage activation lack lineage-restricted expression patterns and thus specificity. Serum levels of the macrophage specific scavenger receptor CD163 were determined by enzyme-linked immunosorbent assay (ELISA) and were found to be highly increased in patients with RHS (median 39.0 mg/L). Significantly lower levels were determined in patients with sepsis (median 9.1 mg/L), acute mononucleosis (median 8.2 mg/L), Leishmania infection (median 6.7 mg/L) and healthy controls (median 1.8 mg/L). Follow-up of patients with a relapsing course of the disease revealed close correlations of sCD163 with clinical disease activity, serum ferritin and other markers of macrophage activity. Large sinusoidal accumulations of CD163 expressing macrophages actively engaged in phagocytosis of blood cells were detected in spleen sections of RHS patients. Our data suggests sCD163 to be a macrophage-specific marker in patients with disorders of inappropriate macrophage activation.

Hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis: a journey of a thousand miles begins with a single (big) step

“…Data from the literature also suggest that serial monitoring of soluble CD163 may be particularly useful. 18 Although HCT should not be unduly delayed, we would suggest that some delays to optimally treat residual active HLH are well justified. Therapy with dexamethasone/etoposide, 4 or prednisone/ATG 13 should be aggressively pursued, if indicated.…”

Gene expression profiling of peripheral blood from patients with untreated new‐onset systemic juvenile idiopathic arthritis reveals molecular heterogeneity that may predict macrophage activation syndrome

“…One of the early events in hemophagocytic lymphohistiocytosis/macrophage activation syndrome is an uncontrolled and persistent expansion of activated T lymphocytes and hemophagocytic macrophages. These macrophages express CD163 (13,14,18), a scavenger receptor that recognizes hemoglobin-haptoglobin complexes (19). CD163 appears to be expressed mainly on alternatively activated phagocytic macrophages performing "scavenger" functions (20,21).…”

Cell-Free Hemoglobin and Its Scavenger Proteins: New Disease Models Leading the Way to Targeted Therapies

“…CD163 is cleaved from monocyte and macrophage cell surfaces by a TNF-a-converting enzyme/A Disintigrin and Metalloproteinase 17 mechanism under conditions of inflammation (Etzerodt et al 2010). The inflammation-linked cleavage and plasma levels of CD163 have been shown to be elevated during general tissue inflammation; the highest concentrations were found in patients with macrophage-activation syndromes (Schaer et al 2005). Endocytosis of the Hb -Hp complex results in cellular delivery of heme and up-regulation of HO-1.…”