Cumulative mean fluorescent intensities of HLA specific antibodies predict antibody mediated rejections after kidney transplantation.

It is still not fully elucidated which pretransplant donor-specific HLA antibodies (DSA) are harmful after kidney transplantation. In particular, it needs to be clarified whether cumulative mean fluorescence intensities (MFI) against multiple HLA specificities have a predictive value for allograft function. Our retrospective single centre study analyzed preformed HLA antibodies determined by Luminex™ Single Antigen Bead (SAB) assay, including C1q addition, in relation to rejection and clinical outcome in 255 cross match negative kidney allograft recipients. Only 33 recipients (13%) of the total cohort showed early AMR during the first year posttransplant, but in patients with pre-transplant DSA the rate was increased to 15 out of 40 (38%). Three year graft survival was significantly shorter in patients with histological signs of AMR compared with patients without AMR or with no biopsy (74%, 92%, and 97%, respectively, p < 0.0001). In patients with HLA-DSA, a cumulative MFI value of all HLA antibodies of more than 103.000 indicated the highest risk for AMR posttransplant (p = 0.01). In conclusion, in patients with HLA-DSA, the cumulative MFI value may help to further stratify the risk of AMR after kidney transplantation.

Sex-specific association of a common GNAS polymorphism with self-reported cognitive empathy in healthy volunteers.

BACKGROUND: In a recent study, we found associations of a common oxytocin receptor (OXTR) polymorphism with inter-individual differences in empathy, especially with emotional empathy in women. Many other studies found specific associations of oxytocin, arginine-vasopressin, serotonin and dopamine receptor gene polymorphisms with various aspects of trait empathy. As all these receptors belong to the guanine-binding protein (G protein) coupled receptor family, it is a reasonable assumption, that alterations in genes encoding G protein subunits also influence the signal transduction in empathy related circuits. However, to the best of our knowledge, these genomic variations have not yet been studied in genetic research on empathy. METHODS: Here, we analysed associations of a common polymorphism of the GNAS gene (C393T) in a previously characterized sample of 421 healthy blood donors (231 M, 190 F; age 18-74). The GNAS gene encodes the G protein adenylyl cyclase stimulator (Gαs) G protein subunit, which activates cyclic adenosine monophosphate (cAMP)-dependent pathways by stimulating the adenylyl cyclase. Cognitive and emotional aspects of dispositional empathy were tested using Davis' Interpersonal Reactivity Index (IRI). RESULTS: In the complete sample, associations of C393T genotype with IRI empathy scores, including cognitive empathy (p = 0.055) and perspective taking (p = 0.057) scores did not reach a level of significance. None of the IRI scores was near to being significantly associated with C393T genotype for men alone. In females, however, genotype was significantly associated with cognitive empathy (r = -.204, p = 0.005) and perspective taking (r = -.209, p = 0.004), accounting for 4.2% and 4.4% of variability. The association of genotype with perspective taking remained significant after adjustment for multiple comparisons (p = 0.045). The 393C-allele, which had been identified as a risk factor in several medical conditions such as hypertension, obesity and diabetes, was associated with higher cognitive empathy compared to the T allele in our sample. CONCLUSIONS: The results suggest a significant association of GNAS C393T genotypes with the cognitive empathic capacity of perspective taking. This association could only be found in female participants.

Association of a Common Oxytocin Receptor Gene Polymorphism with Self-Reported 'Empathic Concern' in a Large Population of Healthy Volunteers.

BACKGROUND: Previous research has linked genomic variations of the oxytocin receptor (OXTR) gene with individual differences in empathy. The impact of these variations on specific cognitive and emotional aspects of empathy, however, remains to be clarified. METHODS: We analysed associations of a common OXTR polymorphism (rs53576) with trait empathy in a sample of 421 blood donors (231 M, 190 F; age 18-74) using the Interpersonal Reactivity Index (IRI) as an established multidimensional self-report measure of empathy. RESULTS: Female sex was significantly associated with higher empathy scores in all IRI scales (p<0.001) with the exception of the cognitive perspective taking scale (p = 0.09). The overall trait empathy score was significantly associated with rs53576 (p = 0.01), with mean scores increasing from AA to GG genotypes. An analysis of the IRI subscores revealed that the polymorphism was especially associated with the emotional empathic concern scale (p = 0.02). Separate analysis of the male and female subgroup revealed a significant association of the polymorphism with female (p = 0.04), but not with male (p = 0.20) empathic concern. A comparison of effect sizes between the groups showed greater effects for women compared to men although effect size differences did not become significant in our sample. CONCLUSIONS: Our findings suggest a significant association of the rs53576 OXTR gene polymorphism with trait empathy and especially with emotional aspects of empathy. This association is possibly weaker or absent in men compared to women.