EFI region 8 Balkan external proficiency testing for HLA typing: Results of 15 years.

Istanbul Medical Faculty, Department of Medical Biology, as the first EFI-accredited HLA laboratory in Turkey since 1999 has been organizing both national and international quality control tests for HLA typing under the banner of the "Balkan external proficiency testing (BEPT)" encompassing countries from EFI regions 8. The first round of BEPT in 2004 was organized for low-resolution HLA-A,-B typing by molecular methods and 12 centres participated in the exercise. In 2005, low-resolution HLA-DR typing was added, and in 2007, low-resolution HLA-C and DQ typing were added to the exercise and 28 centres participated. In 2015, high-resolution (four digits or higher typing) HLA-A,-B,-C,-DR and -DQ typing added to the exercise and 40 centres participated. In the last 2 years, 2017 and 2018, the number of participating centres increased to 48 and 52, respectively. When the distribution of low-resolution typing methods applied in the exercises were investigated, it was found that 82% of the centres in the first round of BEPT in 2004 used PCR-SSP, whereas in the last round in 2018, 26% of the centres preferred SSP, while the rest used SSO (50%) or SSP and SSO (24%) methods. Methods for high-resolution typing were SBT (41%), NGS (18%), SSO (18%), SSP (6%), SBT + NGS (6%) and SBT + SSP (11%). In 15th trial for BEPT, nomenclature mistake rate was 12%, and erroneous result rate was 6% for HLA samples. The most common mistakes in the exercises were nomenclature mistakes. The EFI Standards Version 7.0 is stated "HLA type can be reported using a hyphen if homozygosity is not proven by family studies." In order to provide standard results among HLA laboratories and since accurate HLA typing leads to significant increase of graft and patient survival, quality control exercises should be performed in all HLA-based tests periodically.

The novel HLA-B*39:199 allele identified in a candidate bone marrow donor.

HLA-B*39:199 differs from HLA-B*39:10:01 by a G → A substitution in exon 5 in codon 282.

Oxidative stress and macrophage infiltration in IgA nephropathy.

BACKGROUND: The aim of this study was to evaluate the interactions among serum levels of galactose-deficient IgA1 (Gd-IgA1), oxidative stress and macrophage infiltration and their clinical correlates in patients with IgA Nephropathy (IgAN). METHODS: A total of 47 patients with biopsy-proven primary IgAN, aged between 16 and 79 years, with a follow-up period ≥ 1 year or who showed progression to end stage kidney disease (ESKD) regardless the duration of follow-up were included. Study endpoint was the progression to ESKD. Serum Gd-IgA1 and advanced oxidation protein product (AOPP) levels were measured using ELISA assays. Kidney biopsies were evaluated according to the Oxford MEST-C scoring, with C4d and CD68 staining. RESULTS: Seventeen patients (36%) experienced ESKD during a median follow-up time of 6 years (IQR 3.7-7.5). Serum AOPP levels were correlated with the intensity of glomerular C3 deposition (r = 0.325, p = 0.026), glomerular (r = 0.423, p = 0.003) and interstitial CD68 + cell count (r = 0.298, p = 0.042) and Gd-IgA1 levels (r = 0.289, p = 0.049). Serum Gd-IgA1 levels were correlated with the intensity of C3 deposition (r = 0.447, p = 0.002). eGFR at biopsy (adjusted HR (aHR) 0.979 p = 0.011), and E score (aHR, 8.305, p = 0.001) were associated with progression to ESKD in multivariate analysis. 5-year ESKD-free survival rate was significantly lower in patients with higher E score compared to patients with E score 0 [p = 0.021]. CONCLUSIONS: An increased number of macrophages in the glomerular and tubulointerstitial area may play a role in oxidative stress and complement system activation. Endocapillary hypercellularity is a predictive factor for poor prognosis in IgAN.

PROGRESS STUDY: Progression of chronic kidney disease in children and heat shock proteins.

Various molecular and cellular processes are involved in renal fibrosis, such as oxidative stress, inflammation, endothelial cell injury, and apoptosis. Heat shock proteins (HSPs) are implicated in the progression of chronic kidney disease (CKD). Our aim was to evaluate changes in urine and serum HSP levels over time and their relationships with the clinical parameters of CKD in children. In total, 117 children with CKD and 56 healthy children were examined. The CKD group was followed up prospectively for 24 months. Serum and urine HSP27, HSP40, HSP47, HSP60, HSP70, HSP72, and HSP90 levels and serum anti-HSP60 and anti-HSP70 levels were measured by ELISA at baseline, 12 months, and 24 months. The urine levels of all HSPs and the serum levels of HSP40, HSP47, HSP60, HSP70, anti-HSP60, and anti-HSP70 were higher at baseline in the CKD group than in the control group. Over the months, serum HSP47 and HSP60 levels steadily decreased, whereas HSP90 and anti-HSP60 levels steadily increased. Urine HSP levels were elevated in children with CKD; however, with the exception of HSP90, they decreased over time. In conclusion, our study demonstrates that CKD progression is a complicated process that involves HSPs, but they do not predict CKD progression. The protective role of HSPs against CKD may weaken over time, and HSP90 may have a detrimental effect on the disease course.

Infectious Complications of Induction Therapies in Kidney Transplantation.

BACKGROUND Cytomegalovirus (CMV) and BK virus (BKV) are post-transplant opportunistic viral infections that affect patient and graft survival. This study was designed to evaluate the risk of BKV nephropathy and CMV disease in kidney transplant recipients who received induction therapy with ATG or basiliximab. MATERIAL AND METHODS We retrospectively analyzed information on 257 adult patients who underwent kidney transplantation between January 2007 and 2017. Patients were categorized into 3 groups according to the induction therapies. The primary endpoint was the onset of CMV disease or biopsy-confirmed BKV nephropathy. The secondary endpoints were biopsy-proven rejection episodes, graft loss, loss to follow-up, and death. RESULTS We followed 257 patients for a median of 55.5 months. The incidence of CMV disease was significantly higher in the only ATG group compared to the group without induction treatment (p<0.001). There was no significant difference in the incidence of BKV nephropathy among groups (p>0.05). The dosage of ATG (OR, 10.685; 95% CI, 1.343 5 to 85.009; P=0.025) was independent risk factor for death. CONCLUSIONS This study demonstrated that a higher dosage of ATG in high-risk patients is associated with an increased risk of CMV disease and patient death, also, reducing the dosage may be a rational strategy for increasing graft and patient's survival.