Clinical course and outcome after kidney transplantation in patients with C3 glomerulonephritis due to CFHR5 nephropathy.

BACKGROUND: Complement factor H-related protein 5 (CFHR5) nephropathy is an inherited renal disease characterized by microscopic and synpharyngitic macroscopic haematuria, C3 glomerulonephritis and renal failure. It is caused by an internal duplication of exons 2-3 within the CFHR5 gene resulting in dysregulation of the alternative complement pathway. The clinical characteristics and outcomes of transplanted patients with this rare familial nephropathy remain unknown. METHODS: This is a retrospective case series study of 17 kidney transplant patients with the established founder mutation, followed-up over a span of 30 years. RESULTS: The mean (±SD) age of patients at the time of the study and at transplantation was 58.6 ± 9.9 and 46.7 ± 8.8 years, respectively. The 10- and 15-year patient survival rates were 100 and 77.8%, respectively. Proteinuria was present in 33.3% and microscopic haematuria in 58.3% of patients with a functional graft. Serum complement levels were normal in all. 'Confirmed' and 'likely' recurrence of CFHR5 nephropathy were 16.6 and 52.9%, respectively; however, 76.5% of patients had a functional graft after a median of 120 months post-transplantation. Total recurrence was not associated with graft loss (P = 0.171), but was associated with the presence of microscopic haematuria (P = 0.001) and proteinuria (P = 0.018). Graft loss was associated with the presence of proteinuria (P = 0.025). CONCLUSIONS: We describe for the first time the clinical characteristics and outcome of patients with CFHR5 nephropathy post-transplantation. Despite the recurrence of CFHR5 nephropathy, we provide evidence for a long-term favourable outcome and support the continued provision of kidney transplantation as a renal replacement option in patients with CFHR5 nephropathy.

Psychophysiological and self-reported reactivity associated with social anxiety and public speaking fear symptoms: Effects of fear versus distress.

This study examines psychophysiological and subjective reactivity to anxiety-provoking situations in relation to social anxiety and public speaking fear. We hypothesized that social anxiety symptoms would be associated with similar reactivity across types of imaginary anxiety scenes and not specifically to social anxiety-related scenes. This would be attributed to co-existing depression symptoms. Public speaking fear was expected to be associated with more circumscribed reactivity to survival-threat scenes, due to its association with fearfulness. Community participants imagined standardized anxiety situations, including social anxiety and animal fear scenes, while their physiological reactivity and self-reported emotions were assessed. Findings supported that social anxiety was associated with undifferentiated physiological reactivity across anxiety-provoking situations, except with regards to skin conductance level, which was higher during social anxiety imagery. Public speaking fear was associated with increased reactivity to animal phobia and panic scenes. Covariance analyses indicated that the lack of response specificity associated with social anxiety could be attributed to depression levels, while the specificity associated with public speaking fear could be explained by fearfulness. Findings highlight the need to assess not only primary anxiety symptoms but also depression and fearfulness, which likely predict discrepant reactions of individuals to anxiogenic situations.

Expansion of humoral donor-specific alloreactivity after renal transplantation correlates with impaired graft outcome.

IgG human leukocyte antigen (HLA) antibodies were investigated retrospectively after transplantation in 264 primary renal graft recipients. All patients who developed de novo donor-specific antibodies (DSA) and non-DSA (NDSA) (n = 40, 15.1%) were divided into two groups. Group A consisted of patients (n = 20) with stable good graft function (GGF), and group B consisted of patients (n = 20) who developed rejection and/or graft failure (R/GF). DSA were detected in 23 patients (57.5%). Expansion of humoral alloreactivity with the presence of DSA to more than one graft mismatched antigens and coexistence of HLA class I and II DSA were significantly correlated only with R/GF (p = 0.01). Limitation of alloreactivity to one graft-mismatched antigen was detected mainly in patients with GGF. HLA-DQ DSA alone was found only in patients with GGF (p = 0.1). No significant differences were found between the two patient groups with NDSA. Expansion of the humoral alloreactivity to more than one graft molecule in renal transplant recipients identifies patients at high risk of rejection or graft failure. Limitation of humoral alloreactivity to one graft antigen perhaps associates the presence of regulatory mechanisms with GGF only in specific cases.

HLA-B27 in the Greek Cypriot population: distribution of subtypes in patients with ankylosing spondylitis and other HLA-B27-related diseases. The possible protective role of B*2707.

The major purpose of the present study was to investigate the frequency of human leukocyte antigen (HLA)-B27 alleles in healthy controls and in patients with ankylosing spondylitis (AS) and other HLA-B27-related diseases in the Greek Cypriot population. We selected 102 HLA-B27-positive individuals (60 controls and 42 patients). Typing of the HLA-B27 alleles was performed by polymerase chain reaction amplification with sequence-specific primers. Only two alleles were detected in the patient group: B*2702 (n = 31, 73.8%) and B*2705 (n = 11, 26.2%). The HLA-B*2707 allele was detected (n = 10, 16.7%) only in the healthy controls in addition to the B*2702 (n = 31, 51.7%) and B*2705 (n = 19, 31.7%) alleles. Our results show a restricted number of HLA-B27 subtypes associated with AS and other B27-related diseases and an elevated frequency of the B*2702 allele in the AS patients. The allele B*2707 seems to have a protective role in the population studied because it was found only in the healthy controls.