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ASSOCIATION OF CTLA-4 POLYMORPHISM AND REJECTION STEROID TREATMENT RESPONSE IN KIDNEY TRANSPLANT (KT) PATIENTS.
Ketevan Gendzekhadze MSc , Ramn Montao PhD , Pedro Zerpa MD , Anabela Arminio MD , Candelaria Rodriguez MD , Miguel Zerpa MD, PhD , Julio Castro MD, MSc , Jorge Dominguez MD , Jos Benchimol MD and Pedro Rivas-Vetencourt MD . UCV Un. Inv. Quirrgica ; IVIC Lab. Pat. Cel.y Mol. ; HUC Nefrologa and Caracas Venezuela, HMPC, Nefrologa .

CTLA-4 functions as a negative regulator of T cell proliferation. Recently, a correlation between a reduced inhibitory function of CTLA-4 and the homozigous condition for the allele +49*G/G of the CTLA-4 gene was found. Steroids affect T lymphocyte proliferation, and are utilized as the principal drug to treat kidney acute rejection (KAR). However, some patients are resistant to steroid treatment. The aim of this study was to establish the genetic condition at polymorphic sites +49 and -318 of the CTLA-4 gene in patients with KAR that were resistant or sensitive to steroid treatment. 63 patients receiving either cadaveric (n=30) or living related (n=33) KT were studied. Rejection was determined during clinical follow up by rising creatinine levels and/or allograft biopsy. The dinucleotide polymorphism for both regions at CTLA-4 gene were defined by PCR-RFLP. 30 patients had KAR episodes, 8 of them were steroid resistant. No difference was found at position –318 of the CTLA-4 gene between patients that were steroid resistant or responsive. However, a clear difference (see table) was observed at position +49 of the CTLA-4 gene.
We speculate that the mechanism responsible for KAR in individuals carrying allele +49G of CTLA-4 gene could be an increased proliferation of T lymphocytes, explaining the high rate of steroid responsiveness in this group of patients.

Gene, position, alleleResistant to steroidsSensitive to steroidsP (Fisher Test)
CTLA-4 +49 G positive2190.0031
CTLA-4 +49 G negative63
number of individuals in each group