Table.

Summary of historical and recently published studies (bold) of HDL function in RA

Article	Design	N	HDL parameter	Purpose	Method	Results
Antioxidant capacity
McMahon et al(5)	Cross sectional	48 RA, 72 controls	Antioxidant capacity of apoB- depleted serum	Antioxidant capacity RA vs controls	DCF based cell free assay: control LDL with patient HDL and DCF. Fluorescence with HDL > with LDL= pro-oxidant. ApoB- depleted serum added based on cholesterol concentration.	More RA with pro-oxidant HDL (20.1%) vs controls (4.1%) Pro-oxidant HDL correlated with ESR (SLE and RA combined analysis) Inherent control for HDL-C within assay design
Charles- Schoeman et al(6)	Cross- sectional	132 RA	Antioxidant capacity of purified HDL	Antioxidant capacity RA relative to protein cargo	DCF based cell free assay: control LDL with patient HDL and DCF. Fluorescence with HDL > with LDL= pro-oxidant. HDL by dextran sulfate precipitation then magnetic HDL bead isolation.	Pro-oxidant HDL associated with ↑ESR and hsCRP and ↑DAS28 Altered HDL associated proteins in pro-oxidant HDL Inherent control for HDL within assay design
Gomez Rosso et al.(7)	Cross- sectional	12 active RA (N=4 with CRP>10, N=8 with CRP <10), 10 controls	Antioxidant capacity of purified HDL	Antioxidant capacity of total and small dense HDL RA vs controls	Azo-initiator based cell-free assay: control LDL with patient HDL and azo-initiator. Rate of conjugated dienes formed indicate oxidation.	Oxidation rate of small, dense and total HDL similar in RA and controls RA patients with CRP >10 had ↑ oxidation rates in total HDL (56% ↑) and HDL3c (41% ↑) Antioxidant capacity related to phosphatidic acid composition Inherent control for HDL within assay design
Cholesterol efflux capacity
Charles- Schoeman et al(8)	Cross- sectional	40 RA (N=18 with high DAS, N=7 with low DAS) 40 controls	CEC of purified HDL	CEC difference RA vs Controls	Radiolabelled cholesterol, RAW264.7, dextran + bead isolated HDL.	No difference in CEC in RA vs controls ~ 26% ↓ CEC in RA high vs low DAS28* Inverse association with ESR Inherent control for HDL within assay design
Vivekanandan- Giri et al(9)	Cross- sectional	38 RA (N=20 without and N=18 with known CVD) and 20 healthy controls	CEC of apoB- depleted serum	CEC difference RA vs control, correlation with MPO- specific HDL changes	Radiolabelled cholesterol, J774 macrophages.	~21% ↓CEC in RA vs controls No difference in CEC in RA with vs without CVD RA HDL had greater 3-chlorotyrosine content, which was inversely associated with CEC No adjustment for HDL
Liao et al(10)	Prospective (baseline and after ≥10mg/l reduction in CRP)	90 RA	CEC of apoB- depleted serum	Effect of inflammation on CEC	Radiolabelled cholesterol, J774 macrophages.	↑ CEC by 5.7% after absolute ↓ in CRP by 23.5mg/l NS results after adjusting for change in HDL-C or apoA1 concentrations NS correlation between change in DAS28 and CEC
Ronda et al(11)	Cross- sectional	30 RA, 30 controls	CEC of apoB- depleted serum	Efflux difference of various pathways in RA vs controls	Radiolabelled cholesterol, J774 (ABCA1/aqueous diffusion), Rat hepatoma Fu5AU (SR-B1), Chinese hamster ovary cells (ABCG1).	~15% decreased ABCG1 mediated CEC in RA compared to control subjects* No difference in ABCA1, SRB1 or aqueous diffusion mediated CEC in RA ABCG1 mediated CEC inversely correlated with DAS28, but not with CRP or ESR No adjustment for HDL
Ronda et al(12)	Prospective baseline and 6 weeks/6 months after MTX or ADA+MTX	56 RA (34 MTX, 22 ADA+MTX)	CEC of whole serum	Effect of treatment on CEC by different pathways	Radiolabelled cholesterol, J774 (ABCA1/aqueous diffusion) Rat hepatoma Fu5AU (SR-B1) Chinese hamster ovary cells (ABCG1).	MTX ↑ CEC by ~ 6% via SR-B1 and ~ 7% by ABCG1* ADA+MTX without sustained effect on CEC by any transporter In ADA+MTX users, ABCG1 CEC positive correlation with HDL-C, inverse correlation with DAS28 at month 6, NS correlation with CRP or ESR No adjustment for HDL
Lipid metabolism
Pozzi et al(13)	Cross- sectional	30 RA (N=16 remission, N=15 high DAS), 30 controls	Lipid transfer from LDL to dextran sulfate- MgCl2 precipitated plasma	Ability of HDL to accept lipid from LDL in RA	Radiolabelled nanoemulsion incubated with subject plasma then radioactivity of dextran sulfate- MgCl2 precipitated plasma is measured.	~25% reduction in cholesterol ester transfer in RA compared to controls No difference in any lipid transfer comparing high to low disease activity No adjustment for HDL
Charles- Schoeman et al(14)	Cross- sectional, prospective (before and 6 weeks after tofacitinib)	36 RA and 33 controls	In vivo cholesterol and lipoprotein kinetics	Cholesterol kinetics in RA and change by tofacitinib	22 hour radiolabeled free cholesterol infusion, and 20 hour radiolabelled leucine infusions with frequent plasma measurements.	~12% ↑ in cholesterol ester catabolism in RA vs controls ~8% ↓ in cholesterol ester catabolism in RA after tx No difference in cholesterol efflux rate in RA vs controls or after tx No difference in other cholesterol or lipoprotein kinetics in RA vs controls or after tx

Bold designates recent study.

^*Estimated relative change based on graph. Percent changes are relative, not absolute changes, unless otherwise specified. RA= rheumatoid arthritis, apoB= apolipoprotein B, DCF= dihydrodichlorofluorescein, LDL= low density lipoprotein, HDL= high density lipoprotein, CRP= C-reactive protein, CEC= cholesterol efflux capacity, DAS28= disease activity based on 28 joint count, apoB= apolipoprotein B, apoA1= apolipoprotein A1, ABCG1= ATP-binding cassette sub-family G member 1, ABCA1= ATP-binding cassette sub-family A member 1, SRB1= scavenger receptor class B1.