Significance of caveolin-1 immunohistochemical staining differences in biopsy samples from kidney recipients with BK virus viremia.

BK virus infections which usually remains asymptomatic in healthy adults may have different clinical manifestations in immunocompromised patient population. BK virus reactivation can cause BK virus nephropathy in 8% of kidney transplant patients and graft loss may be seen if not treated. Clathrin or Caveolar system is known to be required for the transport of many viruses from Polyomaviruses family including BK viruses. In this study, kidney transplant patients with BK virus viremia were divided into two groups according to the BK virus nephropathy found in kidney biopsy (Group I: Viremia+, Nephropathy+ / Group II: Viremia+, Nephropathy-). Kidney biopsies were examined with immunohistochemical staining to determine the distribution and density of the Caveolin-1 and Clathrin molecules. Immunohistochemical staining of the 31 pathologic specimens with anti-caveolin-1 immunoglobulin revealed statistically significant difference between group-I and group-II. The number of the specimens stained with anti-caveolin-1 was less in group I. On the other hand, we did not find any difference between the groups regarding the anti-clathrin immunochemical analysis. According to these findings, caveolin-1 expression differences in kidney transplant patients may be important in disease progression.

Report from the extended HLA-DPA1 ~ promoter ~ HLA-DPB1 haplotype of the 18th international HLA and immunogenetics workshop.

The primary goal of the HLA-DPA1 ~ promoter ~ HLA-DPB1 haplotype component of the 18th IHIWS was to characterise the extended haplotypes within the HLA-DP region and survey the extent of genetic diversity in this region across human populations. In this report, we analysed single-nucleotide polymorphisms (SNPs) in 255 subjects from 6 different cohorts. The results from the HLA-DP haplotype component have validated findings from the initial pilot study. SNPs in this region were inherited in strong linkage, particularly HLA-DPA1, SNP-linked promoter haplotypes and motifs in exon 2 of HLA-DPB1. We reported 17 SNP-linked haplotypes in the promoter region. Together with HLA-DPA1 and HLA-DPB1 alleles, they formed 74 distinct extended HLA-DP haplotypes in 438 sequences. We also observed the presence of region-specific alleles and promoter haplotypes. Our approach involved phasing extended SNPs including promoter SNPs, HLA-DPA1 and HLA-DPB1 alleles, in a 22 kb region, GRCh38/hg38 (chr6:33,064,111-33,086,679), followed by clustering of these SNPs as one extended haplotype. This hierarchical clustering revealed four major clades, suggesting that haplotypes within each clade may have diverged from a common ancestral haplotype and undergone similar evolutionary processes. The correlation between HLA-DPA1 and the promoter region raises questions about the role of HLA-DPA1 antigen in the heterodimer. This finding requires validation on a larger sample size specifically designed for anthropological analysis. Nevertheless, the results from this study highlight the clinical potential of selecting better-matched donors for patients awaiting haematopoietic stem cell transplants from genetically overlapping groups that share common ancestral haplotypes.

High soluble CD30 levels and associated anti-HLA antibodies in patients with failed renal allografts.

INTRODUCTION: Serum soluble CD30 (sCD30), a 120-kD glycoprotein that belongs to the tumor necrosis factor receptor family, has been suggested as a marker of rejection in kidney transplant patients. The aim of this study was to evaluate the relationship between sCD30 levels and anti-HLA antibodies, and to compare sCD30 levels in patients undergoing hemodialysis (HD) with and without failed renal allografts and transplant recipients with functioning grafts. METHODS: 100 patients undergoing HD with failed grafts (group 1), 100 patients undergoing HD who had never undergone transplantation (group 2), and 100 kidney transplant recipients (group 3) were included in this study. Associations of serum sCD30 levels and anti-HLA antibody status were analyzed in these groups. RESULTS: The sCD30 levels of group 1 and group 2 (154 ± 71 U/mL and 103 ± 55 U/mL, respectively) were significantly higher than those of the transplant recipients (group 3) (39 ± 21 U/mL) (p<0.001 and p<0.001). The serum sCD30 levels in group 1 (154 ± 71 U/mL) were also significantly higher than group 2 (103 ± 55 U/mL) (p<0.001). Anti-HLA antibodies were detected in 81 (81%) and 5 (5%) of patients in groups 1 and 2, respectively (p<0.001). When multiple regression analysis was performed to predict sCD30 levels, the independent variables in group 1 were the presence of class I anti-HLA antibodies (ß = 0.295; p = 0.003) and age (ß = -0.272; p = 0.005), and serum creatinine (ß = 0.218; p = 0.027) and presence of class II anti-HLA antibodies (standardized ß = 0.194; p = 0.046) in group 3. CONCLUSIONS: Higher sCD30 levels and anti-HLA antibodies in patients undergoing HD with failed renal allografts may be related to higher inflammatory status in these patients.

A male-specific increase in the HLA-DRB4 (DR53) frequency in high-risk and relapsed childhood ALL.

Previous studies reported significant HLA-DR associations with various leukemias one of which is with HLA-DRB4 (DR53) family in male patients with childhood ALL. We have HLA-DR-typed 212 high-risk or relapsed patients with childhood (n=114) and adult (n=98) ALL and a total of 250 healthy controls (118 children, 132 adult) by PCR-SSP analysis. The members of the HLA-DRB3 (DR52) family were underrepresented in patients most significantly for HLA-DRB1*12 (P=0.0007) and HLA-DRB1*13 (P=0.0001). In childhood ALL, the protective effect of DRB3 was evident in homozygous form (P=0.001). The DRB4 marker frequency was increased in males with childhood ALL (67.4%) compared to age- and sex-matched controls (42.1%, P=0.003) and female patients (35.7%, P=0.004). Besides being a general marker for increased susceptibility to childhood ALL in males, HLA-DRB4 is over-represented in high-risk patients. These results further suggest that the HLA system is one of the components of genetic susceptibility to leukemia but mainly in childhood and in boys only.

HLA-DRB1*15 and pediatric aplastic anemia.

We report a positive association between HLA-DRB1*15 (p= 0.0002) in Turkish patients with pediatric severe aplastic anemia (SAA) and a paradoxically favorable influence of the susceptibility marker on the clinical response to immunosuppressive therapy. These findings point to an immune mechanism mediated by DRB1*15 in SAA which confers responsiveness to treatment.