High Prevalence of Anti-Apolipoprotein/A-1 Autoantibodies
in Maintenance Hemodialysis and Association With
Dialysis Vintage
Menno Pruijm,
1
Jan Schmidtko,
1
Anthony Aho,
1
Sabrina Pagano,
2
Pascale Roux-Lombard,
2,3
Daniel Teta,
1
Michel Burnier,
1
and Nicolas Vuilleumier
2
1
Division of Nephrology and Hypertension, Department of Internal Medicine, University Hospital Lausanne,
Lausanne,
2
Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine and
3
Division
of Immunology and Allergy, Department of Internal Medicine, Geneva University Hospital,
Geneva, Switzerland
Abstract: Autoantibodies to apolipoprotein/A-1 (anti-
ApoA-1 IgG) have pro-atherogenic properties in patients
at high cardiovascular risk, but its prevalence in patients
with end-stage kidney disease is unknown. The aims of
this single-center, cross-sectional study were to assess the
prevalence of anti-ApoA-1 antibodies in patients on
maintenance hemodialysis (MHD), and to examine its
correlation with inflammatory biomarkers related to
atherosclerotic plaque vulnerability and dialysis vintage.
To this purpose, anti-ApoA-1 IgG levels and the
concentrations of interleukin-6 (IL-6), interleukin-8
(IL-8), monocyte chemoattractant protein-1 (MCP-1),
metalloproteinase-9 (MMP-9), tumor necrosis factor-a,
and C-reactive protein (CRP) were assessed in the sera of
66 MHD patients (mean age: 68 14 years, 36% women,
32% diabetics). Anti-ApoA-1 IgG positivity (defined as a
blood value 97.5
th
percentile of the normal distribution
as assessed in healthy blood donors) was 20%. Circulating
levels of anti-ApoA-1 IgG correlated positively with
dialysis vintage, but not with cardiovascular risk factors or
previous cardiovascular events; no significant correlations
were found between the anti-ApoA1 IgG levels
and circulating levels of IL-6, IL-8, MCP-1, MMP-9, CRP,
or low-density lipoprotein-cholesterol. In multivariable
linear regression, adjusted for age and sex, only dialysis
vintage remained positively and independently associated
with anti-ApoA-1 titers (b= 0.05, 95% CI: 0.006; 0.28,
P = 0.049). In conclusion, the prevalence of anti-ApoA-1
IgG is raised in the MHD-population, and positively asso-
ciated with dialysis vintage, a major determinant of car-
diovascular outcome. Whether antiApoA-1 antibodies
play a role in the pathophysiology of accelerated athero-
sclerosis in the MHD-population merits further
study. Key Words: Apolipoprotein/A-1, Atherosclerosis,
Autoantibodies, Cardiovascular risk, Inflammation, Main-
tenance hemodialysis.
End-stage renal disease (ESRD) is associated with
a high burden of mortality, mainly due to cardiovas-
cular complications (1). Premature cardiovascular
disease (CVD) in ESRD and maintenance hemodi-
alysis (MHD) patients has been attributed to the
superimposition of both traditional CV and non-
traditional CV risk factors (2). Among the non-
traditional CV risk factors, chronic inflammation may
be a major determinant in ESRD-related atheroscle-
rosis and cardiovascular complications (3), which is
consistent with the current view that atherosclerosis
is an immune-inflammatory driven process (4).
Indeed, circulating levels of inflammatory markers
such as CRP, IL-6, and monocyte chemoattractant
protein-1 (MCP-1) are high and correlated with mor-
tality in ESRD (5–7). There is also cumulating evi-
dence suggesting that both cellular and humoral
immune dysfunction are prevalent in ESRD and
could contribute to ESRD-related CVD (8). To this
respect, low levels of anti-atherogenic antibodies
such as anti-phosphorylcholine IgM, were shown to
Received February 2012; revised May 2012.
Address correspondence and reprint requests to Dr Menno
Pruijm, MD, Chef de Clinique, Department of Nephrology and
Hypertension, University Hospital Lausanne (CHUV), Rue du
Bugnon 17, 1011 Lausanne, Switzerland. Email: mennopruijm@
hotmail.com
Therapeutic Apheresis and Dialysis 2012; 16(6):588–594
doi: 10.1111/j.1744-9987.2012.01102.x
© 2012 The Authors
Therapeutic Apheresis and Dialysis © 2012 International Society for Apheresis
588