impactful in communities than looking
for genetic hieroglyphics common in
false groupings like racial classifications.
Genetic research has already defanged
much of the racial haranguing that even
science has fostered throughout our his-
tory. Ethnic variations as illumined by
Dr. Parsikia and his colleagues are indeed
real and vastly improve our understand-
ing of cultural dynamics that impact in
very real and substantial ways the best
approach to all of our patients.
Joseph Keith Melancon
George Washington University Hospital
Washington D.C.
The author declares no funding or conflicts of interest.
Address correspondence to: Joseph Keith Melancon,
M.D., George Washington Medical Faculty
Associates, 2150 Pennsylvania Avenue NW
suite 6B-412 Washington D.C. 20037.
E-mail: keith_mel@msn.com
Received 10 February 2014. Revision requested
11 February 2014.
Accepted 19 February 2014.
Copyright * 2014 by Lippincott Williams & Wilkins
ISSN: 0041-1337/14/9710-e60
DOI: 10.1097/TP.0000000000000135
CDC Crossmatch and C1qSCREEN in Liver Transplantation
I
read with interest the recent paper by
Kubal et al reporting for the first time the
impact of preformed C1q-fixing positive
donor-specific antibodies (C1q-DSA) using
C1qScreen in liver transplantation (1).
In their introduction, the authors
erroneously cite a paper by Sutherland
et al (2) on kidney transplantation to
support their hypothesis that preformed
C1q-DSA are associated with ACR: ac-
tually, both Sutherland et al (2) and,
more recently, other investigators (3) have
shown that de novo (not preformed, as
studied by Kubal et al) C1q-DSA associate
with AMR, not ACR, in kidney and other
types of solid organ transplantation.
In Table 2, the authors report the
parameter ‘‘percentage of cumulative MFI
of DSA fixing C1q’’(1): that parameter is
a biological nonsense because the MFI of
LabScreen and C1qScreen are not directly
comparable for percentage calculations.
The authors report that ‘‘patients
with autoimmune hepatitis, primary
sclerosing cholangitis, and primary biliary
cirrhosis as a group had a tendency to-
ward [flow cytometry] CM+ status’’
(19% vs. 9%). This finding can be ex-
plained only assuming a high prevalence
of innocuous antilymphocyte (non-anti-
HLA) autoantibodies, commonly found
in autoimmune diseases, which could
have been discriminated by CDC auto-
crossmatching. They also report that
these autoimmune liver disease recipients
had a tendency to develop ACR (9% vs.
2%): it remains to be established whether
those were true ACR or rather relapses
of the underlying cell-mediated hepatic
autoimmune disease (4).
The authors conclude that ‘‘With
the use of rabbit antithymocyte globulinT
rituximab induction, overall low rejection
rates can be achieved in CM+ LT.’’ Be-
cause these therapies are also effective
against the underlying autoimmune liver
disease, although the clinical benefit is
out of discussion, from a mechanistic
point of view, it remains to be understood
whether these immunosuppressants are
only preventing the ACR or also treat-
ing (and preventing recurrence of) the
underlying autoimmune disease. Fur-
thermore, because rabbit ATG also has
anti-CD20 activity (5), and actually
both rituximab-treated and Yuntreated
recipients showed drops in CD19
+
B-lymphocyte counts at month 1, I
wonder whether addition of rituximab
to induction is really worth the cost (1).
The authors report that ‘‘Only
2 out of 112 CM+ patients developed
antibody-mediated rejection (AMR).’’
Such very low positive predictive values
of flow-cytometry crossmatch (FC-XM)
(G2% for AMR, G5% for ACR) should
encourage discontinuation of FC-XM
(and of the less-sensitive and less-specific
CDC-XM) testing in liver transplantation
in the setting of universal induction
therapy. On the contrary, based on excit-
ing results from the kidney transplanta-
tion field and encouraging preliminary
results in the liver transplantation field,
prospective clinical trials implementing
conventional IgG Luminex-based virtual
crossmatches (6Y10) and tailor-made in-
duction immunosuppression and trials
implementing C1qScreen for posttrans-
plantation monitoring and tailor-made
maintenance immunosuppression (3, 11)
should be started.
Daniele Focosi
Division of Transfusion Medicine
and Transplant Biology
Azienda Ospedaliero-Universitaria Pisana
Pisa, Italy
The authors declare no funding or conflicts of interest.
Address correspondence to: Daniele Focosi, M.D.,
via Paradisa 2, 56124 Pisa, Italy.
E-mail daniele.focosi@gmail.com
Received 7 January 2014.
Accepted 28 January 2014.
Copyright * 2014 by Lippincott Williams & Wilkins
ISSN: 0041-1337/14/9710-e61
DOI: 10.1097/TP.0000000000000095
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Crossmatch-positive liver transplantation in
patients receiving thymoglobulin-rituximab
induction. Transplantation 2014; 97: 56.
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Complement-fixing donor-specific anti-
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* 2014 Lippincott Williams & Wilkins Correspondence e61
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