Eun-Young Song

Impact of cytokine gene polymorphisms on risk and treatment outcomes of aplastic anemia.

Autoreactive cytotoxic T cells play a key role in the pathogenesis of aplastic anemia (AA) by myelosuppressive cytokines including interferon-gamma, tumor necrosis factor alpha, and transforming growth factor beta. The purpose of this study is to determine which single nucleotide polymorphisms (SNPs) in cytokine genes were relevant to AA risk and whether the relevant SNPs were associated with response to immunosuppressive therapy (IST). Among 84 screened patients, 80 patients confirmed as having acquired AA, and 84 age- and sex-matched healthy controls were analyzed consecutively. We genotyped ten polymorphisms in three cytokine genes (IFNG, TNF, and TGFB1) and FAS gene. We assessed the association between polymorphisms and AA risk, and the association between polymorphisms and response to IST in three genetic models (dominant, recessive, and additive). The IFNG −2,353 T allele (dominant model, ORu2009=u20090.43, pu2009=u2009.012) and TCA haplotype (dominant model, ORu2009=u20090.50, pu2009=u2009.038) were significantly associated with the development of AA. In addition, this relevant IFNG −2,353 T allele and TCA haplotype were related to the response of IST (dominant model, ORu2009=u20090.076, pu2009=u2009.034). Concerning TGFB1, although its polymorphisms are not related to AA susceptibility, P10L T allele (recessive model, ORu2009=u20090.18, pu2009=u2009.038) and CT haplotype (dominant model, ORu2009=u20095.68, pu2009=u2009.038) were associated with response to IST. This exploratory study concurred with prior studies indicating that polymorphisms in IFNG are related to AA susceptibility. In addition, it was found that polymorphisms in IFNG and TGFB1 are associated with response to IST.

Hypoplastic myelodysplastic syndrome (h-MDS) is a distinctive clinical entity with poorer prognosis and frequent karyotypic and FISH abnormalities compared to aplastic anemia (AA)

The aims of the present study are two-fold: (1) to define the clinical features of hypoplastic myelodysplastic syndrome (h-MDS) in comparison with aplastic anemia (AA) and (2) to evaluate the prognostic roles of karyotyping and fluorescent in situ hybridization (FISH) in these hypoplastic marrow syndromes. Based on a medical record review at Seoul National University Hospital, the records of 409 patients diagnosed with either h-MDS or AA were evaluated. Of these patients, 358 had been diagnosed with AA and 51 with h-MDS (median age, 39 years). At diagnosis, 235 and 165 patients underwent karyotyping and FISH analysis, respectively. Karyotypic abnormalities and trisomy 8 and trisomy 1q FISH abnormalities were found more frequently in h-MDS patients than in AA patients. Median overall survival (OS) of h-MDS patients was shorter than that of AA patients (83 vs. 201 months, P=0.007), with the OS of h-MDS patients falling between that of severe and very severe AA patients. Patients with h-MDS had more frequent leukemic conversion (P<0.001) than did AA patients. In AA patients, karyotypic abnormality was not prognostic (P=0.646), while in h-MDS patients, abnormalities in trisomy 1q FISH (P=0.002) and in 20q deletion FISH (P=0.005) were predictive of poor prognosis. In conclusion, the prognosis for h-MDS patients falls between that of severe and very severe AA patients. Moreover, h-MDS is frequently accompanied by karyotypic and FISH abnormalities and is prone to leukemic conversion. Trisomy 1q and 20q deletion FISH abnormalities may have important prognostic roles in patients with h-MDS.

Possession of the macrophage-induced gene by isolates of the Mycobacterium avium complex is not associated with significant clinical disease.

The Mycobacterium avium complex (MAC) is the most frequently isolated species among non-tuberculous mycobacteria (NTM) clinical isolates. Physicians pay attention to the differential diagnosis of the disease caused by MAC from tuberculosis because of their similar clinical presentations. Expression of the macrophage-induced gene (mig) is one of the virulence phenotypes in MAC, but it has not been determined whether the presence of the mig gene itself has any relationship with clinical disease or whether it is merely a marker for MAC. To uncover the significance of the mig gene among MAC clinical isolates, positive cultures from respiratory specimens from patients in a tertiary referral centre were identified by sequencing the 16S rRNA gene. The mig gene was also evaluated using PCR and sequence analysis. The medical records from the patients were reviewed retrospectively. The diagnostic criteria from the American Thoracic Association were adopted for the diagnosis of NTM lung disease. A total of 45 MAC clinical isolates were identified over a period of 1 year. Following 16S rRNA sequencing, all of the 23 M. avium isolates were categorized as sequevar I. Among the 22 Mycobacterium intracellulare isolates, 18 strains were identified as M. intracellulare sequevar I and the remaining four consisted of one each of sequevars II, III, IV and V. The proportion of cases that fitted the diagnostic criteria of NTM lung disease was 26.7 % (12/45). The mig PCR results were 100 % positive for the MAC isolates studied, irrespective of their species, sequevar or disease-causing properties. However, following bootstrap analysis of the mig sequences, we observed definite grouping between M. avium and M. intracellulare. Thus the mig gene is a species-specific marker with distinct sequence diversity between the two species M. avium and M. intracellulare, but there is poor correlation between disease-causing properties and specific mig sequences.

Trend, not severity, of acute kidney injury affects graft outcome in deceased donor kidney transplantation

Deceased donor kidneys (DDKs) with acute kidney injury (AKI) are difficult to allocate for fear of the expected graft outcome. We aimed to evaluate the impact of donors’ AKI severity and trend on graft outcomes in DDK transplantation. This was a retrospective study of DDK transplantation performed from 2005 to 2014. Based on maximum and terminal serum creatinine values before transplantation, the AKI trends were categorized as improving or worsening. Of 413 DDKs, 275 developed AKI: 177 stage 1, 52 stage 2, and 46 stage 3. DDKs with AKI had 212 improving AKI and 63 worsening AKI. Graft outcomes were similar based on AKI stage. Worsening AKI did not affect delayed graft function development; however, it significantly elevated graft failure risk even after adjusting for AKI stage and Kidney Donor Risk Index. Graft survival of the improving group was similar to DDKs with no AKI. This study showed that AKI severity of DDKs did not affect overall graft outcomes. Notably, DDKs with improving AKI showed a similar graft survival rate to DDKs without AKI, although worsening AKI had a worse prognosis. Consideration of the AKI trend, rather than its severity, is needed when DDKs with AKI are allocated.

Evaluation of LABType® SSO HLA Typing using the Luminex Platform: Cord Blood Registry Typing for the Korean Population

BACKGROUNDnThe performance of a new intermediate-resolution method using a PCR-Luminex platform and LABType® SSO A, B DRB1 kits as an HLA typing method for the cord blood (CB) registry of the Korean population was investigated.nnnMETHODSnA total of 1,413 cord blood units (CBUs) were enrolled - 1,382 from Koreans and 31 from non-Koreans or mixed-ancestry individuals. HLA-A, -B, and -DRB1 typing was performed using the LABType® SSO typing kits. HLA typing with the DNA method and 2-digit results are mandatory for the public CB bank in Korea according to the CB Act.nnnRESULTSnThe proportions of ambiguous results in the 2-digit assignment were 14.6% (206/1,413) and 14.8% (205/ 1,382) among the total subjects and the Korean donors, respectively. In the 2-digit resolution, 3 different HLA-A types (69 CBUs), 31 HLA-B types (124 CBUs), and 3 HLA-DRB1 types (13 CBUs) showed ambiguous results. The most probable type to the ambiguous results based on the reported Korean HLA allele frequencies were able to be assigned. The most probable results were 100% consistent with the confirmed types as determined by the HD kits (DRB1) and additional PCR-SBT or PCR-SSP tests (A and B). Luminex technology is more automated and less labor intensive than the conventional SSO typing method, and the results are less affected by differences between inspectors.nnnCONCLUSIONSnAlthough it is not satisfactory as a sole confirmation test and cannot be used as a replacement for the PCR-SBT test, the combination of Luminex technology with LABType® SSO kits and population frequency data provides a proper typing platform that can be used as a qualifying test for CB registries.