http://www.cnr.it/ontology/cnr/individuo/prodotto/ID192379
C1Q-FIXING HLA ANTIBODIES AND KIDNEY GRAFT OUTCOME (Abstract/Poster in rivista)
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- Label
- C1Q-FIXING HLA ANTIBODIES AND KIDNEY GRAFT OUTCOME (Abstract/Poster in rivista) (literal)
- Anno
- 2012-01-01T00:00:00+01:00 (literal)
- Alternative label
Antonina Piazza1, Daniela Caputo2, Elvira Poggi1,
Giuseppina Ozzella1, Rosa Cremona2, Anna Rita
Manfreda2, Cecilia Palombi2, Domenico Adorno2 (2012)
C1Q-FIXING HLA ANTIBODIES AND KIDNEY GRAFT OUTCOME
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- Antonina Piazza1, Daniela Caputo2, Elvira Poggi1,
Giuseppina Ozzella1, Rosa Cremona2, Anna Rita
Manfreda2, Cecilia Palombi2, Domenico Adorno2 (literal)
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- 1CNR IFT UOS Roma San Camillo, Centro Regionale Trapianti - Lazio, Rome, Italy,
2Centro Regionale Trapianti - Lazio, Rome, Italy (literal)
- Titolo
- C1Q-FIXING HLA ANTIBODIES AND KIDNEY GRAFT OUTCOME (literal)
- Abstract
- Development of de novo donor-specific HLA antibodies (DSA)
represents the major risk factor for graft failure in kidney
transplantation. However, some patients show persistent presence
of circulating DSA without occurrence of graft dysfunction/
loss. The complement-dependent citotoxicity (CDC) assay
has demonstrated low sensitivity in detecting DSA. Newer solid
phase assays, such as Luminex Single Antigen (LSA) beads, are
highly sensitive but less predictive of transplant outcome because
of detection of both complement-fixing and no complementfixing
HLA antibodies. It has been suggested that discrimination
between potentially harmful complement-fixing DSA and
presumably less harmful no complement-fixing DSA could be
clinically relevant in kidney transplantation. Using a modified
LSA assay that identifies antibodies able to fix C1q, we investigated
the clinical relevance of de novo complement-fixing DSA
on kidney graft outcome. In serum samples from 40 kidney
transplanted patients who developed IgG-LSA DSA after transplantation,
we measured C1q-DSA using Class I and Class II
LSA beads. Twenty-three of the 40 patients showed production of
C1q-positive DSA; the remaining 17 patients had C1q-negative
DSA. Correlating graft outcome and capability of DSA to fix
C1q, we evidenced that graft failure due to antibody-mediated
rejection occurred in 20 of the 23 patients showing C1q-positive
DSA; only 2 of the 17 patients showing C1q-negative DSA suffered
graft failure (87% vs. 12% respectively, p < 0.0001). Both
C1q-positive and C1q-negative DSA were mainly specific for the
DQ mismatched molecules of the donor (74% and 53% respectively).
Analyzing the target molecules of DQ-specific DSA, we
evidenced that 9 of the 17 (53%) anti-DQ C1q-positive DSA
were specific for DQ1 molecules while 6 of the 8 (75%) anti-
DQ C1q-negative DSA were specific for DQ2 molecules. In
conclusion our data demonstrate that C1q-LSA assay has the
capability to identify the subset of IgG-LSA DSA strongly associated
with graft failure (RR = 7.39) in kidney transplantation.
Moreover the ability of C1q assay in distinguishing less harmful
no complement-fixing DSA from clinically relevant C1qfixing
DSA represent a non-invasive tool for identifying patients
that need specific immunosuppressive therapy to prolong graft
survival. (literal)
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