GlycA is not a useful biomarker of inflammation in sickle cell disease

Sickle cell disease (SCD) is a multisystemic disorder, the pathology being driven by recurrent inflammation particularly during a vaso-occlusive crisis. GlycA, a composite measure of protein glycation, is a sensitive biomarker for disorders associated with vascular inflammation. We determined the utility of GlycA as a biomarker of inflammation in SCD.

Stored plasma samples from patients with SCD recruited to two clinical studies were analyzed. One study encompasses 488 patient samples with SCD (HbSS, HbSβ⁰ and HbSC) at steady state and 52 race-matched, healthy controls. The other study included paired plasma samples during steady state and acute pain crisis from (HbSS) patients with SCD. Plasma GlycA was measured using a proton NMR on the Vantera^® Clinical Analyzer. We performed analysis comparing patients with SCD, healthy controls, and paired samples analysis.

The mean plasma GlycA level was lower in SCD compared with healthy controls (324.6 ± 70.4 micromol/L vs. 386.3 ± 74.6 micromol/L, P < 0.0001). Within the same patient, mean plasma GlycA during acute pain crisis was lower than steady state, although the difference was not significant (300.5 ± 36.3 micromol/L vs 314.2 ± 34.8 micromol/L, P = 0.020). Plasma GlycA correlated inversely with serum LDH (P = 0.009).

GlycA is not a suitable biomarker of inflammation in SCD. We surmise that its signal is confounded by hemolysis leading to a depletion of haptoglobin, one of the major plasma proteins included in the composite NMR signal. Hemolysis is further exacerbated during an acute pain crisis, hence the lower GlycA levels in crisis compared to steady state.