Kwang-Sook Woo

Primary anti-D Immunization by DEL Red Blood Cells

Extremely weak D variants called DEL are serologically detectable only by adsorption-elution techniques. A nucleotide change of exon 9 in RHD gene, RHD (K409K, 1227G>A) allelic variant is present in almost all the DEL individuals of East Asians. No DEL phenotype has yet been shown to induce a primary alloanti-D immunization in East Asia. A 68-yr-old D-negative Korean man was negative for anti-D at admission, and he developed alloanti-D after transfusion of red blood cells (RBC) from 4 apparently D-negative donors. Four donors who typed D-negative by routine serologic test were analyzed by real-time PCR for RHD gene and RHD (K409K). One donor was found to have RHD (K409K). This is the first case in which DEL RBCs with RHD (K409K) induced a primary alloanti-D immunization in Asian population. Because the DEL phenotype can induce an anti-D immunization in D-negative recipients, further discussion is needed whether RhD negative donors should be screened by molecular method and what an efficient genotyping method is for detecting the RHD gene carriers in Korea.

Serial Interferon-gamma Release Assays for the Diagnosis of Latent Tuberculosis Infection in Patients Treated with Immunosuppressive Agents

Background We assessed the efficacy of serial interferon-gamma release assays (IGRAs) for the diagnosis of latent tuberculosis infection (LTBI) in patients receiving immunosuppressive agents for treatment of rheumatic diseases in Korea. Methods Of 276 patients who underwent consecutive screening with one of two IGRAs [QuantiFERON-TB Gold or QuantiFERON-TB Gold In-Tube], 66 patients were evaluated by the serial IGRA for detection of LTBI during therapy with immunosuppressive agents. Information on clinical diagnosis, medication, previous TB, blood cell count, tuberculin skin test, and interferon-gamma (IFN-γ) level measured by IGRA was collected. Results Of the 66 patients, the initial IGRA was positive in 24.2%, negative in 65.2%, and indeterminate in 10.6%. Forty-six patients (69.7%) showed consistent IGRA results during follow-up, and 13 patients (19.7%) had consistently positive results. IGRA conversion rate was 12.1% (8/66) and reversion rate was 4.5% (3/66). Conversion of IGRA results was only observed in ankylosing spondylitis patients, and the median interval between the two tests in patients with conversion was 8.5 months. The mean IFN-γ level in the group of patients with consistently positive IGRA results was higher than that in the group with inconsistently positive results, although this trend was not statistically significant (P=0.293). Indeterminate results were observed most frequently in patients with systemic lupus erythematosus. Conclusions In patients receiving immunosuppressive agents, both IGRA conversions and reversions were observed. Serial IGRA testing may not be needed in patients with a positive initial IGRA result showing high IFN-γ levels, because of high consistency in the test results.

Urinary Neutrophil Gelatinase-Associated Lipocalin Levels in Comparison with Glomerular Filtration Rate for Evaluation of Renal Function in Patients with Diabetic Chronic Kidney Disease

Background Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker of acute kidney injury. There is a growing body of evidence suggesting that NGAL is also a marker of kidney disease and severity in chronic kidney disease (CKD). We studied the utility of urinary NGAL in more accurately predicting renal function in patients with diabetic CKD. Methods We studied possible relationships between urinary NGAL, estimated glomerular filtration rate (eGFR), and proteinuria in diabetic CKD patients and in healthy populations. Results Urinary NGAL levels were significantly higher in CKD patients than in healthy controls (96.0 [2.7 to 975.2] ng/mL vs. 18.8 [1.3 to 81.9] ng/mL, P=0.02), and the GFR was lower among CKD patients (49.3 [13.1 to 78.3] mL/min/1.73 m2 vs. 85.6 [72 to 106.7] mL/min/1.73 m2, P<0.0001). The urinary NGAL level showed a significant inverse correlation with GFR (r=-0.5634, P<0.0001). The correlation analyses between urinary protein level and urinary NGAL levels and GFR were as follows: urine protein and urinary NGAL (r=0.3009, P=0.0256), urine protein and GFR (r=-0.6245, P<0.0001), urine microalbumin and urinary NGAL (r=0.1794, P=0.2275), and urine microalbumin and GFR (r=-0.5190, P=0.0002). Conclusion From these results, we concluded that urinary NGAL is a reliable marker of renal function in diabetic CKD patients. However, urinary NGAL did not provide more accurate information regarding renal function than GFR.

Prevalence and clinical associations of lupus anticoagulant, anticardiolipin antibodies, and anti-beta2-glycoprotein I antibodies in patients with systemic lupus erythematosus.

BACKGROUND The presence of antiphospholipid antibodies (aPLs) is associated with the clinical features of antiphospholipid syndrome (APS), which comprises venous and arterial thrombosis and pregnancy loss, and systemic lupus erythematosus (SLE). The prevalence of aPLs has been reported to be different in patient populations affected by either of these conditions. We performed a retrospective study to evaluate the prevalence and clinical associations of aPLs, including lupus anticoagulant (LAC), anticardiolipin (aCL), and anti-beta2-glycoprotein I antibodies (anti-beta2-GPI) in a cohort of Korean patients with SLE. METHODS This study included samples from 88 SLE patients for whom aPL testing had been advised between June 2006 and July 2009 at the Dong-A University Hospital. Serum and plasma samples were tested for LAC, aCL (IgG, IgM), and anti-beta2-GPI (IgG, IgM) antibodies. Clinical data from patients were obtained from a review of medical records. RESULTS LAC was the most common (34.1% of total patients, 30/88) antibody, followed by IgM aCL (31.8%, 28/88), IgG aCL (18.2%, 16/88), and IgM and IgG anti-beta2-GPI (both 5.7%, 5/88 each). Positivity for LAC was strongly associated with venous/arterial thrombosis (P=0.002). CONCLUSIONS LAC was the most common antibody detected in Korean SLE patients and is shown to have a significant association with the presence of venous/arterial thrombosis. The measurement of LAC may be clinically useful in identifying patients with SLE who are at a high risk for venous/arterial thrombosis.

Clinical Usefulness of Serum Cystatin C as a Marker of Renal Function

Background Accurate renal function measurements are important in the diagnosis and treatment of kidney diseases. In contrast to creatinine, the production of serum cystatin C has been extensively reported to be unaffected by body muscle mass, age, gender, and nutritional status. Methods Our study included 37 samples from diabetic chronic kidney disease (CKD) patients for whom serum creatinine tests had been requested and 40 samples from a healthy populations in Dong-A University Hospital between May 2010 and June 2010. The assay precision (i.e., the coefficient of variation) and the reference range of the serum cystatin C test were evaluated. We compared the estimated glomerular filtration rates (GFRs) based on cystatin C with those based on creatinine. Moreover, we investigated the influences of age, gender, weight, and muscle mass on serum creatinine and serum cystatin C. Results There was a positive correlation between GFR based on creatinine and that based on cystatin C (r=0.79, P<0.0001) among the diabetic CKD patients. Serum creatinine and cystatin C were significantly correlated with body weight and muscle mass, but the strengths of these correlations were greater for serum creatinine. The precision study revealed excellent results for both the high and low controls. The 95% reference interval of cystatin C in the healthy population was 0.371 to 1.236 mg/L. Conclusion Based on these results, we conclude that, despite the strong correlation between serum creatinine and cystatin C, cystatin C is less affected by weight and muscle mass and might represent a better alternative for the assessment of renal function.

Outbreak of Pseudomonas Oryzihabitans Pseudobacteremia Related to Contaminated Equipment in an Emergency Room of a Tertiary Hospital in Korea

Pseudomonas oryzihabitans is frequently found in various sites within hospital settings, including sink drains and respiratory therapy equipment. Although it rarely causes human infections, P. oryzihabitans has recently been considered a potential nosocomial pathogen, especially in immunocompromised hosts. We report our experience of an outbreak of P. oryzihabitans pseudobacteremia, presumably due to faulty aseptic preparation of a saline gauze canister.

Evaluation of the leukocyte differential on a new automated flow cytometry hematology analyzer.

Introduction:  The Hematoflow (Beckman Coulter, USA) is a new automated hematology analyzer, which provides a 16‐part white blood cell count (WBC) differential.

Relationship between the Levels of Holotranscobalamin and Vitamin B12

To date, the determination of serum vitamin B12 levels has been the most common laboratory test for the assessment of vitamin B12 status; however, the diagnostic accuracy of this test is low. To obtain a more sensitive marker, a new test to measure holotranscobalamin (holoTC) levels has been introduced. In this study, we assessed 45 patients for whom a vitamin B12 test had been requested and 139 anemic patients. We investigated the associations between the levels of homocysteine (Hcy) and those of holoTC, serum vitamin B12, and folate and assessed the diagnostic value of holoTC levels as a marker for vitamin B12 deficiency. We also determined the precision of the AxSYM holoTC assay by calculating the coefficient of variance (CV). The within-run and between-run precision values were excellent, as all CV values were less than 3.5%. The holoTC levels were low (<35 pmol/L) in 7 samples, and 6 of these samples had normal total serum vitamin B12 levels. In 2 of these samples, high Hcy levels (>12 micromol/L) indicated vitamin B12 deficiency. Thus, the holoTC levels were more sensitive than the serum vitamin B12 levels for indicating vitamin B12 status. If the serum vitamin B12 level is 151-300 pmol/L, the levels of holoTC alone or in combination with serum vitamin B12 levels are likely to be more useful markers than serum vitamin B12 levels alone.

A de novo Proximal 6q Deletion Confirmed by Array Comparative Genomic Hybridization

Deletions of chromosome 6q, particularly in the proximal region, are relatively rare. Here, we report on a de novo interstitial deletion of (6)(q13q16.2) in a girl with facial dysmorphism, congenital hip dislocation, porencephaly, and brain atrophy. Array comparative genomic hybridization analysis showed arr 6q13q16.2(73,378,824?99,824,130), demonstrating higher resolution than the conventional cytogenetic findings, del(6)(q12q15). The clinical data were analyzed and compared with those of similar patients previously reported in the literature.

Number of megakaryocytic progenitors and adhesion molecule expression of stem cells predict platelet engraftment after allogeneic hematopoietic stem cell transplantation

BACKGROUND The mechanism of platelet recovery after hematopoietic stem cell transplantation and the factors that influence its time-course are not fully understood. Rapid hematopoietic recovery results in a reduction of transplantation-related complications. In the present study, we questioned and analyzed whether there were important factors predicting the speed of platelet engraftment. METHODS Thirty-seven patients with various hematologic diseases transplanted with allogeneic BM between January 2002 and December 2005 were included. We investigated the differences in mononuclear cell counts (MNC), numbers of infused CD34(+), CD34(+) CD41(+) and CD34(+) CD61(+) cells and phenotypic analysis of homing-associated cell adhesion molecules (CXCR4, CD49d and CD49e). The number of megakaryocytes formed in vitro (colony-forming unit-megakaryocytes; CFU-Mk) was also measured. RESULTS Median days of ANC >/=0.5x10(9)/L and platelet count >/=20x10(9)/L were 14.8 and 17.3, respectively. The number of infused CD34(+) CD41(+) and CD34(+) CD61(+) cells correlated much better with the time to platelet engraftment than that of infused CD34(+)cells (P<0.05 each). Rapid platelet recovery also occurred in patients receiving both higher homing-associated cell adhesion molecule doses and CFU-Mk (P<0.05 each). DISCUSSION Rapid platelet recovery has several advantages, including reducing the cost of supportive therapy and reducing the risk of fatal bleeding as a result of severe thrombocytopenia. Our findings suggest that phenotypic and clonogenic assessment of infused progenitor cells can identify patients in whom platelet engraftment is likely to be significantly delayed, and new strategies to overcome related problems might be employed in the very near future.