Kidney International (2012) 81
The authors are funded by grants from
Science Foundation Ireland (grants SFI PI
06 / IN.1 / B652 and SFI SRC 09 / SRC / B1794 to
MDG) and from the Health Research Board
of Ireland (grant NSAFP / 2010 / 1 to BAM).
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see original article on page 1239
Does IgA antibody against
? 2 glycoprotein I increase
cardiovascular risk in
hemodialysis patients ?
Rajesh K. Patel 1 and Roopen Arya 1
Th e risk of cardiovascular disease is high
in patients with chronic kidney disease,
and cardiovascular disease accounts for up
to 50 % of deaths in this population. In the
subset of patients receiving hemodialysis
the rate of cardiovascular mortality is 10 – to
20 – fold higher than that of the general
population. 1 In addition to a high preva-
lence of traditional cardiovascular risk
factors in patients with chronic renal
disease (for example, hypertension and
diabetes mellitus), other specific risk
factors, including degree of uremia,
comorbidity, inflammatory response,
hypoalbuminemia, and hyperparathy-
roidism, also seem to contribute to the
excess cardiovascular risk.
Th e antiphospholipid syndrome (APS)
is an acquired, strongly prothrombotic
disease characterized by arterial and ven-
ous thromboembolism and / or pregnancy
morbidity in the presence of persistent
high-titer autoantibodies directed against
a broad range of phospholipids and phos-
pholipid-binding proteins. 2 Th e history of
APS dates back to reports in the 1950 s
of false-positive laboratory test results
for syphilis in patients who went on
to develop systemic lupus erythema tosus
(SLE). It became apparent that Wasserman
et al. had detected the earliest anti-phos-
pholipid antibodies in 1906 with the
development of a complement-fi xation
assay for syphilis using phospholipid anti-
gen from hepatic extract of fetuses with
congenital syphilis. 3 Th is phospho lipid
antigen was later named ‘ cardiolipin ’ (as
subsequently mitochondrial phospholip-
ids were extracted from bovine heart mus-
cle), and anti-cardiolipin antibody
detection became the basis of the current-
day Venereal Disease Research Laboratory
(VDRL) test for syphilis. Widespread
screening of donated blood for syphilis led
to the realization that some patients with
SLE possessed anti-phospholipid antibod-
ies resulting in false-positive VDRL tests,
prolonged laboratory clotting times, and
strong predisposition to thrombosis.
Anti-phospholipid antibodies are
detected either by a prolongation of phos-
pholipid-dependent coagulation tests
(lupus anticoagulant) or by solid-phase
immune assays. Th ey are a heterogeneous
group of autoantibodies directed against
a variety of diff erent antigens (including
prothrombin, annexin V, protein C, and
protein S); it is thought that binding of
these antigens is at least partly responsible
for the prothrombotic phenotype of APS.
In the early 1990s, several groups reported
that a proportion of anti-cardiolipin anti-
bodies were directed against the phos-
pholipid cofactor ? 2 glycoprotein I
( ? 2GPI). Th is single-chain polypeptide
glycoprotein is a 50 – kDa plasma apolipo-
protein (plasma concentration 200 ? g / ml)
that binds anionic phospholipids; it is
required for anti-phospholipid antibody
binding in a subset of patients with SLE
Cardiovascular disease is the most common cause of mortality in
patients with chronic kidney disease on hemodialysis. In addition to a
high prevalence of traditional cardiovascular risk factors, other specific
factors, including uremia and chronic inflammation, seem to contribute
to the excess cardiovascular mortality. The findings of Serrano et al.
point to a link between IgA antibodies against ? 2 glycoprotein I
and cardiovascular events in renal dialysis patients.
Kidney International (2012) 81, 1164 – 1166. doi: 10.1038/ki.2012.35
1 King ’ s Thrombosis Centre, Department of
Haematological Medicine, King ’ s College Hospital ,
London , UK
Correspondence: Roopen Arya, King ’ s Thrombosis
Centre, Department of Haematological Medicine,
King ’ s College Hospital, Denmark Hill, London
SE5 9RS, UK. E-mail: firstname.lastname@example.org