Comprehensive Analysis of the HLA Class I and the HLA class II Alleles in Patients with Takayasu Arteritis: Relationship with Clinical Patterns and Prognosis

Background: Takayasu arteritis (TA) is a systemic vasculitis, affecting mainly the aorta and its branches. Objective: To analyze the HLA class I and class II alleles in patients with TA and explore their relationship with clinical and demographic characteristics, and potential significance in prognosis. Methods: Twenty-five, unrelated TA patients were genotyped for HLA-A, HLA-B, HLA-C, HLA-DRB1, and the HLA-DQB1 loci. The frequencies of the HLA-A, HLA-B, and the HLA-DRB1 were compared with a control group of 1992, while the HLA-C and the HLA-DQB1 were compared with a group of 159 healthy, unrelated individuals. Results: Among TA patients, 5/25 (20%) were identified as the HLA-B*52 carriers. There was a significant difference in the HLA-B*52 allele frequency in the TA patients (10%) compared with the healthy controls (1.2%). Moreover, presence of the HLA-B*52 was associated with significantly earlier disease onset, more severe clinical presentations, and a poorer response to treatment. The HLA-C*03 was detected in 32% of patients and was present exclusively in those with a clinically mild form of the TA, indicating a putative protective effect. Conclusion: These findings indicate that the HLA-B*52 allele contributes to a higher susceptibility to the TA whereas the HLA-C*03, can be a protective factor in the TA.     

Characterization of eleven polymorphic microsatellite markers for leafhoppers of the genus Aphrodes (Hemiptera: Cicadellidae)

Eleven microsatellite markers were developed for the leafhoppers of the genus Aphrodes using shotgun pyrosequencing and will be used to study the genetic diversity, population structure and gene flow within and between species in this genus in order to assess their conservation status. The number of alleles per locus ranged from 3 to 10, while observed and expected heterozygosity values varied from 0.421–1.000 to 0.542–0.876, respectively. Cross-species amplification was successful among the four congeners.     

Inter-laboratory study on standardized MPS libraries: evaluation of performance,concordance, and sensitivity using mixtures and degraded DNA

International Journal of Legal Medicine - We present results from an inter-laboratory massively parallel sequencing (MPS) study in the framework of the SeqForSTRs project to evaluate forensically...     

Conversion from twice- to once-daily tacrolimus in pediatric kidney recipients: a pharmacokinetic and bioequivalence study

Background

The objectives of this study were to investigate pharmacokinetic and pharmacogenetic parameters during the conversion on a 1:1 (mg:mg) basis from a twice-daily (Prograf) to once-daily (Advagraf) tacrolimus formulation in pediatric kidney transplant recipients.

Methods

Twenty-four-hour pharmacokinetic profiles were analyzed before and after conversion in 19 stable renal transplant recipients (age 7–19 years). Tacrolimus pharmacokinetic parameters [area under the concentration-time curve (AUC_0–24), minimum whole-blood concentration (C_min), maximum whole-blood concentration (C_max), and time to achieve maximum whole-blood concentration (t_max)] were compared between Tac formulations and between CYP3A5 and MDR1 genotypes after dose normalization.

Results

Both AUC_0–24 and C_min decreased after conversion (223.3 to 197.5 ng.h/ml and 6.5 to 5.6 ng/ml; p?=?0.03 and 0.01, respectively). However, the ratio of the least square means (LSM) for AUC_0–24 was 90.8 %, with 90 % CI limits of 85.3 to 96.7 %, falling within bioequivalence limits. The CYP3A5 genotype influences the dose-normalized C_min with the twice-daily formulation only.

Conclusions

Both tacrolimus formulations are bioequivalent in pediatric renal recipients. However, we observed a decrease in AUC_0–24 and C_min after the conversion, requiring close pharmacokinetic monitoring during the conversion period.     

C-kit overexpression is not associated with KIT gene mutations in chromophobe renal cell carcinoma or renal oncocytoma

Introduction

C-kit overexpression has previously been described in chromophobe renal cell carcinoma (cpRCC) and renal oncocytoma (RO). However, so far no KIT mutations have been found. The objective of our study was to analyse c-kit in a large cohort of renal tumors and to perform KIT mutation analysis in a subset cpRCC and RO cases with overexpression of c-kit.

Materials and methods

We studied the immunohistochemical expression of c-kit on tissue microarrays containing formalin-fixed, paraffin-embedded samples of 948 patients with renal tumors. CpRCC and RO cases with c-kit overexpression (n = 23) were analyzed for KIT mutations in exons 9, 11, 13, 14, 15, and 17.

Results

Expression of c-kit was found in 6/642 (0.9%) clear cell RCC, 3/154 (1.9%) papillary RCC, 54/69 (78.3%) cpRCC, 37/45 (82.2%) RO and 2/30 (6.7%) of other unclassified tumor types. In none of the RO and cpRCC cases analyzed, a KIT gene mutation was found.

Conclusion

C-kit expression is found in the majority of cpRCC and RO, but these tumors do not harbor the usual c-kit activating mutations. This may have implications for the use of tyrosine kinase inhibitors in patients with advanced cpRCC and c-kit expression.