Serum p-Glycoprotein and Monomeric C-Reactive Protein are Elevated in Takayasu Arteritis

Purpose: Existing biomarkers including C-reactive protein (CRP) do not adequately distinguish active and inactive TAK. We compared serum p-glycoprotein (p-gp)/Multidrug Resistance Protein 1 (MDR1), monomeric CRP (mCRP), CRP, and mCRP:CRP ratio in Takayasu arteritis (TAK) and healthy controls and their relationship with disease activity.

Patients and methods: Serum p-gp mCRP (ELISA) and CRP (nephelometry) were compared between consecutive adults with TAK (>18 years) enrolled from a prospective cohort (n = 92) and healthy controls (n = 29), and between active vs inactive TAK (n = 46 each). In a subset of active immunosuppressive-naïve TAK (n = 29), correlation was assessed between serum p-gp and p-gp expression on circulating T helper lymphocyte populations: overall (CD4+), Th17 (CD4+IL-17+), Th17.1 (CD4+IL-17+IFN-γ+) lymphocytes [normalized to Tregs (CD4+CD25+FoxP3+)]. Changes in serum p-gp, mCRP, CRP, and mCRP:CRP were compared before and after immunosuppression (n = 29). Data was represented using median (Q1-Q3). Receiver operating characteristics (ROC) curves were generated for TAK vs controls, and active vs inactive TAK with serum p-gp, mCRP, CRP, and mCRP:CRP. Multivariable-adjusted linear regression was used to predict active disease with serum p-gp, mCRP, CRP, or mCRP:CRP.

Results: Serum p-gp (11.19 vs 8.05 ng/mL), mCRP (1.61 vs 1.25 µg/L), and CRP (5.40 vs 2.1 mg/L) were elevated in TAK vs controls (p <0.05 for all). CRP was higher and mCRP:CRP ratio was lower in active vs inactive TAK (p < 0.001). ROC curves identified moderate prediction for active disease with CRP and inactive disease with serum p-gp (area under ROC curve 0.705 and 0.392, respectively). Multivariable-adjusted linear regression confirmed association of CRP with active disease (p = 0.009) and serum p-gp with inactive disease (p = 0.041). In treatment-naïve TAK, serum p-gp negatively correlated with p-gp+Th17.1 lymphocytes (Spearman's rho=-0.39, p = 0.046). CRP and serum p-gp were significantly lowered following immunosuppressive therapy in treatment-naïve TAK (p < 0.05).

Conclusion: Serum p-gp and mCRP are elevated in TAK. Serum p-gp is associated with inactive disease.