RESEARCH - Anti-atherogenic and anti-inflammatory properties of HDL are affected by specific antibodies in SLE

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Rheumatology Advance Access published online on November 10, 2008

Rheumatology, doi:10.1093/rheumatology/ken397

Anti-atherogenic and anti-inflammatory properties of high-density

lipoprotein are affected by specific antibodies in systemic lupus

erythematosus

J. R. Batuca1, P. R. J. Ames2, M. Amaral1,3, C. Favas3, D. A.

Isenberg4 and J. Delgado Alves1,3

1Pharmacology Department, Faculty of Medical Sciences of Lisbon,

Lisbon, Portugal, 2Immunoclot Ltd, Leeds, UK, 3Autoimmune Diseases

Unit, Curry Cabral Hospital, Lisbon, Portugal, 4Centre for

Rheumatology, University College London, London, UK

Abstract

Objective. To determine whether antibodies against high-density

lipoprotein (aHDL) and apolipoprotein A-I (aApo A-I) interfere with

the anti-atherogenic functions of high-density lipoprotein (HDL) and

relate to disease activity and damage in SLE.

Methods. Seventy-seven SLE patients were compared with an age- and

sex-frequency matched control group. Immunoglobulin G (IgG) aHDL, IgG

aApoA-I, soluble vascular cell and intracellular cell adhesion

molecules (VCAM-1 and ICAM-1, respectively) were measured by ELISA,

paraoxonase (PON) activity by spectrophotometry, nitric oxide (NOx)

metabolites by the Griess reaction, and total anti-oxidant capacity

(TAC) by chemiluminescence.

Results. Compared with controls, SLE patients showed higher titres of

IgG aHDL (P < 0.0001) and IgG aApo A-I (P < 0.0001), lower PON

activity (P < 0.0001), increased NOx (P < 0.0001), VCAM-1 (P < 0.0001)

and ICAM-1 (P = 0.0008) and lower TAC (P = 0.0006). Titres of IgG aHDL

positively correlated with IgG aApo A-I (r = 0.64, P < 0.0001), NOx (r

= 0.32, P = 0.007), inversely correlated with PON activity (r = –0.34,

P = 0.002) and TAC (r = –0.43, P = 0.0004) and were independently

associated with ICAM-1 (t = 3.509, P = 0.001). IgG aApo A-I titres

correlated positively with NO (r = 0.37, P = 0.007), inversely with

PON activity (r = –0.31, P = 0.006), TAC (r = –0.47, P < 0.0001) and

were independently associated with HDL (t = –2.747, P = 0.008) and

VCAM-1 (t = 3.311, P = 0.002), the latter alongside NOx (T = 2.271, P

= 0.02). Elevated titres of IgG aHDL and IgG aApo A-I and reduced PON

activity related to increased disease score (BILAG) and damage index

(SLICC/ACR DI).

Conclusion. In SLE, IgG aHDL and aApo A-I associate with disease

activity and damage and interfere with the anti-oxidant and

anti-inflammatory functions of HDL favouring atherogenesis.

http://rheumatology.oxfordjournals.org/cgi/content/abstract/ken397v1?papetoc

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