Pre-transplant donor biopsy (PTDB)-based marginal-donor allocation systems to single or dual renal transplantation could increase the use of organs with Kidney Donor Profile Index (KDPI) in the highest range (e.g. >80 or >90), whose discard rate approximates 50% in the US. To test this hypothesis, we retrospectively calculated the KDPI and analyzed the outcomes of 442 marginal kidney transplants (340 single transplants: 278 with a PTDB Remuzzi score <4 [median KDPI:87; interquartile range(IQR):78-94] and 62 with a score =4 [median KDPI:87; IQR:76-93]; 102 dual transplants [median KDPI: 93; IQR:86-96]) and 248 single standard transplant controls [median KDPI:36; IQR:18-51]. PTDB-based allocation of marginal grafts led to a limited discard rate of 15% for kidneys with KDPI of 80-90 and of 37% for kidneys with a KDPI of 91-100. Although 1-year eGFRs were significantly lower in recipients of marginal kidneys (-9.3, -17.9, and -18.8ml/min, for dual transplants, single kidneys with PTDB score <4, and =4, respectively; P<0.001), graft survival (median follow-up 3.3 years) was similar between marginal and standard kidney transplants (hazard ratio: 1.20 [95% confidence interval: 0.80 to 1.79; P=0.38]). In conclusion, PTDB-based allocation allows the safe transplantation of kidneys with KDPI in the highest range that may otherwise be discarded.

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To compare the functional features of circulating and intrahepatic hepatitis C virus (HCV)-specific CD4؉ T cells in chronic HCV infection, peripheral blood and liver-infiltrating lymphocytes from 29 patients with chronic hepatitis C were stimulated with structural and nonstructural HCV proteins to produce antigen-specific T-cell lines and clones. Antigen specificity, fine specificity, phenotype, cytokine production, and T-cell receptor (TCR)-v␤ chain expression were analyzed. The results indicate a hierarchy of stimulatory capacity by the different HCV proteins, core being the antigen most frequently recognized by CD4؉ intrahepatic lymphocytes, followed by NS4 and NS5. The CD4 response was directed simultaneously against different HCV proteins in individual patients, but fine-specificity analysis indicated that the response was generally focused on a limited number of immunodominant epitopes. Although the narrowly focused nature of this response may favor the emergence of escape mutations, this event was not observed by following-up over time the sequence of 2 epitopes strongly immunodominant for intrahepatic CD4 cells of a patient with chronic HCV infection. In conclusion, simultaneous analysis of peripheral blood and intrahepatic CD4 cells in the same patients indicated a predominant Th1 profile of HCV-specific CD4 cells and suggests a specific compartmentalization of virus-specific T cells into the liver.

Purpose: We evaluated the impact of the killer immunoglobulin-like receptors (KIR) of natural killer (NK) cells and of their HLA ligands over the clinical outcome of hepatitis C virus (HCV)-related hepatocellular carcinoma after curative treatment by either surgical resection or radiofrequency thermal ablation (RTA).Experimental Design: Sixty-one consecutive patients with HCV-related hepatocellular carcinoma underwent KIR genotyping and HLA typing. A phenotypic/functional characterization of NK cells was carried out in patients with different KIR/KIR-ligand genotype.Results: Activating KIR2DS5 was associated with significantly longer time to recurrence (TTR) and overall survival (OS; P < 0.03 each). Homozygous HLA-C1 (P < 0.02) and HLA-Bw4I80 (P < 0.05) were expressed by patients with significantly better OS, whereas HLA-C2 (P < 0.02) and HLA-Bw4T80 (P < 0.01) were associated with a worse OS. Multivariate analysis identified as parameters independently related to TTR the type of treatment (surgical resection vs. RTA; P < 0.03) and HLA-C1 (P < 0.03), whereas only KIR2DS5 was an independent predictor of longer OS (P < 0.05). Compound KIR2DL2-C1 and KIR3DS1-Bw4T80 genotypes were associated with better TTR (P < 0.03) and worse OS (P ¼ 0.02), respectively. A prevalent cytotoxic (CD56 dim ) NK phenotype was detected in patients with both longer TTR and OS. Cytotoxic capacity measured by upregulation of CD107a was significantly higher in subjects with HLA-C1 alone or combined with KIR2DL2/KIR2DL3. Conclusions: These results support a central role of NK cells in the immune response against hepatocellular carcinoma, providing a strong rationale for therapeutic strategies enhancing NK response and for individualized posttreatment monitoring schemes.

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Eighty systemic lupus erythematosus (SLE) patients attending 3 clinical centers were evaluated immunologically and immunogenetically. No HLA class I1 antigens were found to be significantly associated with SLE in these patients. A highly significant (P = 6.17 X lo-') association was observed between anticardiolipin antibodies and DR7. A lesser association (P < 0.025) was also observed between DR2 and/or DR3 and anti-Ro (SS-A) antibodies. No relationship was found between any DR antigen and anti-Sm/RNP, antidouble-stranded DNA, or anti-La (SS-B) antibodies.In the last 10 years, studies of (New Zealand black x New Zealand white)F, murine lupus-like disease have disclosed some association between certain autoimmune traits and the H2 system, the murine major histocompatibility complex (MHC) (1). These

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We report the first case in Italy of a non-Ashkenazi double heterozygote for BRCA1 and BRCA2 genes. This finding is predictably rare, with a maximum frequency of 1/250,000. The proband and her mother were diagnosed with early-onset breast cancer. No other relatives with breast and/or ovarian cancer were observed. The implications of this case in regard to genetic testing and counseling are substantial.