correspondence
n engl j med 370;1 nejm.org january 2, 2014 83
As Macchia and colleagues highlight, our data
show that the change in 6-minute walk distance
was not associated with long-term outcomes in
pulmonary arterial hypertension. The observed
reduction in morbidity was driven by a decrease
in the rate of worsening of pulmonary arterial
hypertension, which was defined in great detail
and required three criteria, not only a decrease
in the 6-minute walk distance. Our study was
approved by health authorities and ethics com-
mittees. Background therapy for pulmonary ar-
terial hypertension, when available, was allowed,
and we closely monitored patients for the need for
additional treatment. In some countries, because
of the limited availability of approved targeted
therapies, a patient’s participation in a clinical
trial may provide the only access to potential
treatment for pulmonary arterial hypertension.
Tomás Pulido, M.D.
Ignacio Chávez National Heart Institute
Mexico City, Mexico
Lewis J. Rubin, M.D.
University of California, San Diego
La Jolla, CA
Gérald Simonneau, M.D.
Université Paris-Sud
Le Kremlin-Bicêtre, France
Since publication of their article, the authors report no fur-
ther potential conflict of interest.
1. Graf C, Battisti WP, Bridges D, et al. Research methods and
reporting: good publication practice for communicating com-
pany sponsored medical research: the GPP2 guidelines. BMJ
2009;339:b4330.
2. AMWA position statement on the contribution of medical
writers to scientific publications. Rockville, MD: American
Medical Writers Association (http://www.amwa.org).
3. Jacobs A, Wager E. European Medical Writers Association
(EMWA) guidelines on the role of medical writers in developing
peer-reviewed publications. Curr Med Res Opin 2005;21:317-22.
4. Norris R, Bowman A, Fagan JM, et al. International Society
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DOI: 10.1056/NEJMc1313112
Complement-Binding Anti-HLA Antibodies and Kidney
Transplantation
To the Editor: Loupy et al. (Sept. 26 issue)
1
present data showing that the C1q-binding assay
is more sensitive than the standard complement-
dependent microlymphocytotoxicity (CDL) assay
for assessing the risk of graft loss. In their retro-
spective analysis of 1016 patients who had a neg-
ative CDL assay before transplantation, antibody-
mediated rejection developed in 7.4% during the
first year. The authors predict that antibody-me-
diated rejection would have occurred in 3.7% of
patients (a 50% reduction) if the C1q-binding as-
say had been used.
However, most laboratories use a more sen-
sitive flow cytometric crossmatching (FCXM),
2
not CDL alone. We have data from 11 patients
who had low levels of donor-specific anti-HLA
antibodies (mean fluorescence intensity [MFI],
<3500 arbitrary fluorescence units) on the single-
antigen Luminex bead assay, negative FCXM, and
negative C1q-binding assay (<100 MFI units)
Table 1. Levels of Donor-Specific Anti-HLA Antibodies in Four Patients with Antibody-Mediated Rejection after Kidney
Transplantation.*
Patient
Number Before Transplantation After Transplantation
Luminex Assay C1q Assay Luminex Assay C1q Assay
1 B72 (MFI, 1632); CW2
(MFI, 4758)
B72 (MFI, 0); CW2
(MFI, 0)
B72 (MFI, 3123); CW2
(MFI, 8214)
B72 (MFI, 21,609); CW2
(MFI, 10,096)
2 B8 (MFI, 350); A23
(MFI, 1237)
B8 (MFI, 100); A23
(MFI, 0)
B8 (MFI, 4115); A23
(MFI, 1166)
B8 (MFI, 1839); A23
(MFI, 157)
3 B49 (MFI, 0); DQ2
(MFI, 275)
B49 (MFI, 16); DQ2
(MFI, 0)
B49 (MFI, 8888); DQ2
(MFI, 1094)
B49 (MFI, 1609); DQ2
(MFI, 638)
4 B37 (MFI, 871); B51
(MFI, 473)
B37 (MFI, 0); B51
(MFI, 24)
B37 (MFI, 2669); B51
(MFI, 618)
B37 (MFI, 1115); B51
(MFI, 386)
* The mean fluorescence intensity (MFI) was measured in arbitrary fluorescence units.
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