PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-18 (18)
 

Clipboard (0)
None

Select a Filter Below

Journals
more »
Year of Publication
1.  Multicenter Retrospective Analysis of the Effectiveness and Safety of Rituximab in Korean Patients with Refractory Systemic Lupus Erythematosus 
Autoimmune Diseases  2012;2012:565039.
Objective. Although two recent randomized placebo-controlled trials of rituximab (RTX) failed to demonstrate efficacy in systemic lupus erythematosus (SLE), clinicians continue to use off-label RTX for cases refractory to current treatments. We evaluated the effectiveness and safety of rituximab for patients with refractory SLE in Korea. Methods. We retrospectively analyzed multicenter patients treated with RTX in Korea. Results. 39 SLE patients treated with RTX were included in the following manner: lupus nephritis 43.6%, hematologic 33.3%, arthritis 7.8%, myositis 7.8%, and others 7.7%. All patients had responded poorly to at least one conventional immunosuppressive agent (mean 2.5 ± 1.1, cyclophosphamide 43.6%, mycophenolate mofetil 48.7%, and other drugs) before RTX. Clinical improvements (complete or partial remission) occurred in patients with renal disease, hematologic disease, arthritis, myositis, and other manifestations at 6 months after RTX. The SLEDAI score was significantly decreased from 10.8 ± 7.1 at baseline to 6.7 ± 4.0 at 6 months, 6.2 ± 4.1 at 12 months, and 5.5 ± 3.6 at 24 months after RTX (P < 0.05). Among 28 clinical responders, 4 patients experienced a relapse of disease at 25 ± 4 months. Infections were noted in 3 patients (7.7%). Conclusion. RTX could be an effective and relatively safe therapeutic option in patients with severe refractory SLE until novel B-cell depletion therapy is available.
doi:10.1155/2012/565039
PMCID: PMC3523406  PMID: 23304457
2.  Construction and Application of a Korean Reference Panel for Imputing Classical Alleles and Amino Acids of Human Leukocyte Antigen Genes 
PLoS ONE  2014;9(11):e112546.
Genetic variations of human leukocyte antigen (HLA) genes within the major histocompatibility complex (MHC) locus are strongly associated with disease susceptibility and prognosis for many diseases, including many autoimmune diseases. In this study, we developed a Korean HLA reference panel for imputing classical alleles and amino acid residues of several HLA genes. An HLA reference panel has potential for use in identifying and fine-mapping disease associations with the MHC locus in East Asian populations, including Koreans. A total of 413 unrelated Korean subjects were analyzed for single nucleotide polymorphisms (SNPs) at the MHC locus and six HLA genes, including HLA-A, -B, -C, -DRB1, -DPB1, and -DQB1. The HLA reference panel was constructed by phasing the 5,858 MHC SNPs, 233 classical HLA alleles, and 1,387 amino acid residue markers from 1,025 amino acid positions as binary variables. The imputation accuracy of the HLA reference panel was assessed by measuring concordance rates between imputed and genotyped alleles of the HLA genes from a subset of the study subjects and East Asian HapMap individuals. Average concordance rates were 95.6% and 91.1% at 2-digit and 4-digit allele resolutions, respectively. The imputation accuracy was minimally affected by SNP density of a test dataset for imputation. In conclusion, the Korean HLA reference panel we developed was highly suitable for imputing HLA alleles and amino acids from MHC SNPs in East Asians, including Koreans.
doi:10.1371/journal.pone.0112546
PMCID: PMC4232350  PMID: 25398076
3.  Targeted exon sequencing fails to identify rare coding variants with large effect in rheumatoid arthritis 
Introduction
Although it has been suggested that rare coding variants could explain the substantial missing heritability, very few sequencing studies have been performed in rheumatoid arthritis (RA). We aimed to identify novel functional variants with rare to low frequency using targeted exon sequencing of RA in Korea.
Methods
We analyzed targeted exon sequencing data of 398 genes selected from a multifaceted approach in Korean RA patients (n = 1,217) and controls (n = 717). We conducted a single-marker association test and a gene-based analysis of rare variants. For meta-analysis or enrichment tests, we also used ethnically matched independent samples of Korean genome-wide association studies (GWAS) (n = 4,799) or immunochip data (n = 4,722).
Results
After stringent quality control, we analyzed 10,588 variants of 398 genes from 1,934 Korean RA case controls. We identified 13 nonsynonymous variants with nominal association in single-variant association tests. In a meta-analysis, we did not find any novel variant with genome-wide significance for RA risk. Using a gene-based approach, we identified 17 genes with nominal burden signals. Among them, VSTM1 showed the greatest association with RA (P = 7.80 × 10−4). In the enrichment test using Korean GWAS, although the significant signal appeared to be driven by total genic variants, we found no evidence for enriched association of coding variants only with RA.
Conclusions
We were unable to identify rare coding variants with large effect to explain the missing heritability for RA in the current targeted resequencing study. Our study raises skepticism about exon sequencing of targeted genes for complex diseases like RA.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-014-0447-7) contains supplementary material, which is available to authorized users.
doi:10.1186/s13075-014-0447-7
PMCID: PMC4203956  PMID: 25267259
4.  Genetics of rheumatoid arthritis contributes to biology and drug discovery 
Okada, Yukinori | Wu, Di | Trynka, Gosia | Raj, Towfique | Terao, Chikashi | Ikari, Katsunori | Kochi, Yuta | Ohmura, Koichiro | Suzuki, Akari | Yoshida, Shinji | Graham, Robert R. | Manoharan, Arun | Ortmann, Ward | Bhangale, Tushar | Denny, Joshua C. | Carroll, Robert J. | Eyler, Anne E. | Greenberg, Jeffrey D. | Kremer, Joel M. | Pappas, Dimitrios A. | Jiang, Lei | Yin, Jian | Ye, Lingying | Su, Ding-Feng | Yang, Jian | Xie, Gang | Keystone, Ed | Westra, Harm-Jan | Esko, Tõnu | Metspalu, Andres | Zhou, Xuezhong | Gupta, Namrata | Mirel, Daniel | Stahl, Eli A. | Diogo, Dorothée | Cui, Jing | Liao, Katherine | Guo, Michael H. | Myouzen, Keiko | Kawaguchi, Takahisa | Coenen, Marieke J.H. | van Riel, Piet L.C.M. | van de Laar, Mart A.F.J. | Guchelaar, Henk-Jan | Huizinga, Tom W.J. | Dieudé, Philippe | Mariette, Xavier | Bridges, S. Louis | Zhernakova, Alexandra | Toes, Rene E.M. | Tak, Paul P. | Miceli-Richard, Corinne | Bang, So-Young | Lee, Hye-Soon | Martin, Javier | Gonzalez-Gay, Miguel A. | Rodriguez-Rodriguez, Luis | Rantapää-Dahlqvist, Solbritt | Ärlestig, Lisbeth | Choi, Hyon K. | Kamatani, Yoichiro | Galan, Pilar | Lathrop, Mark | Eyre, Steve | Bowes, John | Barton, Anne | de Vries, Niek | Moreland, Larry W. | Criswell, Lindsey A. | Karlson, Elizabeth W. | Taniguchi, Atsuo | Yamada, Ryo | Kubo, Michiaki | Liu, Jun S. | Bae, Sang-Cheol | Worthington, Jane | Padyukov, Leonid | Klareskog, Lars | Gregersen, Peter K. | Raychaudhuri, Soumya | Stranger, Barbara E. | De Jager, Philip L. | Franke, Lude | Visscher, Peter M. | Brown, Matthew A. | Yamanaka, Hisashi | Mimori, Tsuneyo | Takahashi, Atsushi | Xu, Huji | Behrens, Timothy W. | Siminovitch, Katherine A. | Momohara, Shigeki | Matsuda, Fumihiko | Yamamoto, Kazuhiko | Plenge, Robert M.
Nature  2013;506(7488):376-381.
A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological datasets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here, we performed a genome-wide association study (GWAS) meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ~10 million single nucleotide polymorphisms (SNPs). We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 1012–4. We devised an in-silico pipeline using established bioinformatics methods based on functional annotation5, cis-acting expression quantitative trait loci (cis-eQTL)6, and pathway analyses7–9 – as well as novel methods based on genetic overlap with human primary immunodeficiency (PID), hematological cancer somatic mutations and knock-out mouse phenotypes – to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
doi:10.1038/nature12873
PMCID: PMC3944098  PMID: 24390342
5.  Variation in the ICAM1–ICAM4–ICAM5 locus is associated with systemic lupus erythematosus susceptibility in multiple ancestries 
Annals of the rheumatic diseases  2012;71(11):1809-1814.
Objective
Systemic lupus erythematosus (SLE; OMIM 152700) is a chronic autoimmune disease for which the aetiology includes genetic and environmental factors. ITGAM, integrin αΜ (complement component 3 receptor 3 subunit) encoding a ligand for intracellular adhesion molecule (ICAM) proteins, is an established SLE susceptibility locus. This study aimed to evaluate the independent and joint effects of genetic variations in the genes that encode ITGAM and ICAM.
Methods
The authors examined several markers in the ICAM1–ICAM4–ICAM5 locus on chromosome 19p13 and the single ITGAM polymorphism (rs1143679) using a large-scale case–control study of 17 481 unrelated participants from four ancestry populations. The single marker association and gene–gene interaction were analysed for each ancestry, and a meta-analysis across the four ancestries was performed.
Results
The A-allele of ICAM1–ICAM4–ICAM5 rs3093030, associated with elevated plasma levels of soluble ICAM1, and the A-allele of ITGAM rs1143679 showed the strongest association with increased SLE susceptibility in each of the ancestry populations and the trans-ancestry meta-analysis (ORmeta=1.16, 95% CI 1.11 to 1.22; p=4.88×10−10 and ORmeta=1.67, 95% CI 1.55 to 1.79; p=3.32×10−46, respectively). The effect of the ICAM single-nucleotide polymorphisms (SNPs) was independent of the effect of the ITGAM SNP rs1143679, and carriers of both ICAM rs3093030-AA and ITGAM rs1143679-AA had an OR of 4.08 compared with those with no risk allele in either SNP (95% CI 2.09 to 7.98; p=3.91×10−5).
Conclusion
These findings are the first to suggest that an ICAM–integrin-mediated pathway contributes to susceptibility to SLE.
doi:10.1136/annrheumdis-2011-201110
PMCID: PMC3466387  PMID: 22523428
6.  A Case of Peritoneal Tuberculosis Developed after Infliximab Therapy for Refractory RA 
Recently, interferon gamma releasing assay has been recommended to compensate the tuberculin skin test (TST) for screening for latent tuberculosis infection (LTBI). Although it improved the detection of LTBI before treatment with tumor necrosis factor blocker, its application to immune suppressed patients is limited. We report a case of peritoneal tuberculosis (TB) developed in a patient who tested positive for TST and QuantiFERON-TB Gold (QFT-G) before infliximab therapy, to emphasize the importance of monitoring during treatment. A 52-year-old woman presented with abdominal distension. She had been diagnosed with seropositive rheumatoid arthritis six years ago. She had started taking infliximab six months ago. All screening tests for TB were performed and the results of all were negative. At admission, the results of repeated TST and QFT-G tests were positive. Histopathological examination confirmed peritoneal TB. The patient started anti-TB therapy and the symptoms were relieved.
doi:10.4046/trd.2012.73.4.234
PMCID: PMC3492425  PMID: 23166560
Peritonitis, Tuberculous; Infliximab
7.  Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis 
Nature genetics  2012;44(3):291-296.
The genetic association of the major histocompatibility complex (MHC) to rheumatoid arthritis risk has commonly been attributed to HLA-DRB1 alleles. Yet controversy persists about the causal variants in HLA-DRB1 and the presence of independent effects elsewhere in the MHC. Using existing genome-wide SNP data in 5,018 seropositive cases and 14,974 controls, we imputed and tested classical alleles and amino acid polymorphisms for HLA-A, B, C, DPA1, DPB1, DQA1, DQB1, and DRB1 along with 3,117 SNPs across the MHC. Conditional and haplotype analyses reveal that three amino acid positions (11, 71 and 74) in HLA-DRβ1, and single amino acid polymorphisms in HLA-B (position 9) and HLA-DPβ1 (position 9), all located in the peptide-binding grooves, almost completely explain the MHC association to disease risk. This study illustrates how imputation of functional variation from large reference panels can help fine-map association signals in the MHC.
doi:10.1038/ng.1076
PMCID: PMC3288335  PMID: 22286218
8.  A fatal case of hepatitis B virus (HBV) reactivation during long-term, very-low-dose steroid treatment in an inactive HBV carrier 
Clinical and molecular hepatology  2012;18(2):225-228.
Hepatitis B virus (HBV) may be reactivated after chemotherapy or immunosuppressive therapy, and therefore administration of antiviral agents before such treatment is recommended. Most reported cases of reactivation are associated with high doses of immunosuppressive agents or combination therapy. We present a case of a previously inactive HBV carrier with an acute severe flare-up during a long-term, very-low-dose (2.5 mg/day) steroid treatment for rheumatoid arthritis. We suggest that even a minimal dose of single-regimen oral steroid can cause reactivation of indolent, inactive HBV.
doi:10.3350/cmh.2012.18.2.225
PMCID: PMC3415881  PMID: 22893874
Hepatitis B virus; Liver failure; Steroids; Virus activation
9.  Lack of Association of Caucasian Rheumatoid Arthritis Susceptibility Loci in a Korean Population 
Arthritis and rheumatism  2009;60(2):364-371.
Objective
Recent studies have identified a number of novel rheumatoid arthritis (RA) loci in Caucasian populations. In this study, we sought to determine whether the genetic variants at 4q27, 6q23, CCL21, TRAF1/C5, and CD40 identified in Caucasians are also associated with RA in a Korean case-control collection. We also comprehensively evaluated the genetic variation within PTPN22, a well established autoimmune disease-associated gene.
Methods
We designed a Sequenom iPlex experiment to thoroughly evaluate the PTPN22 linkage disequilibrium region using tag SNPs and disease-associated SNPs at 5 other previously reported Caucasian RA-associated loci in 1123 RA Korean RA patients and 1008 ethnically matched controls. We also re-sequenced the PTPN22 gene to look for novel coding variants that might be contributing to disease in this population.
Results
None of the Caucasian RA susceptibility loci contributed significantly to disease in Koreans. Tag SNPs covering the PTPN22 linkage disequilibrium block, while polymorphic, did not reveal any disease association and re-sequencing did not identify any new common coding region variants in this population. The 6q23 and 4q27 SNPs assayed were non-polymorphic in this population and the TRAF1/C5, CD40, and CCL21 SNPs did not show any evidence for association.
Conclusions
Caucasian and Korean rheumatoid arthritis have different genetic risk factors. While patients of different ethnic groups share the HLA region as a major genetic risk locus, most other genes shown to be significantly associated with disease in Caucasians appear not to play a role in Korean RA.
doi:10.1002/art.24245
PMCID: PMC2770844  PMID: 19180477
10.  STAT4 and the Risk of Rheumatoid Arthritis and Systemic Lupus Erythematosus 
The New England journal of medicine  2007;357(10):977-986.
BACKGROUND
Rheumatoid arthritis is a chronic inflammatory disease with a substantial genetic component. Susceptibility to disease has been linked with a region on chromosome 2q.
METHODS
We tested single-nucleotide polymorphisms (SNPs) in and around 13 candidate genes within the previously linked chromosome 2q region for association with rheumatoid arthritis. We then performed fine mapping of the STAT1-STAT4 region in a total of 1620 case patients with established rheumatoid arthritis and 2635 controls, all from North America. Implicated SNPs were further tested in an independent case-control series of 1529 patients with early rheumatoid arthritis and 881 controls, all from Sweden, and in a total of 1039 case patients and 1248 controls from three series of patients with systemic lupus erythematosus.
RESULTS
A SNP haplotype in the third intron of STAT4 was associated with susceptibility to both rheumatoid arthritis and systemic lupus erythematosus. The minor alleles of the haplotype-defining SNPs were present in 27% of chromosomes of patients with established rheumatoid arthritis, as compared with 22% of those of controls (for the SNP rs7574865, P = 2.81×10-7; odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.32). The association was replicated in Swedish patients with recent-onset rheumatoid arthritis (P = 0.02) and matched controls. The haplotype marked by rs7574865 was strongly associated with lupus, being present on 31% of chromosomes of case patients and 22% of those of controls (P = 1.87×10-9; odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.55). Homozygosity of the risk allele, as compared with absence of the allele, was associated with a more than doubled risk for lupus and a 60% increased risk for rheumatoid arthritis.
CONCLUSIONS
A haplotype of STAT4 is associated with increased risk for both rheumatoid arthritis and systemic lupus erythematosus, suggesting a shared pathway for these illnesses.
doi:10.1056/NEJMoa073003
PMCID: PMC2630215  PMID: 17804842
11.  Several Regions in the Major Histocompatibility Complex Confer Risk for Anti-CCP-Antibody Positive Rheumatoid Arthritis, Independent of the DRB1 Locus 
Molecular Medicine  2008;14(5-6):293-300.
Recent evidence suggests that additional risk loci for RA are present in the major histocompatibility complex (MHC), independent of the class II HLA-DRB1 locus. We have now tested a total of 1,769 SNPs across 7.5Mb of the MHC located from 6p22.2 (26.03 Mb) to 6p21.32 (33.59 Mb) derived from the Illumina 550K Beadchip (Illumina, San Diego, CA, USA). For an initial analysis in the whole dataset (869 RA CCP + cases, 1,193 controls), the strongest association signal was observed in markers near the HLA-DRB1 locus, with additional evidence for association extending out into the Class I HLA region. To avoid confounding that may arise due to linkage disequilibrium with DRB1 alleles, we analyzed a subset of the data by matching cases and controls by DRB1 genotype (both alleles matched 1:1), yielding a set of 372 cases with 372 controls. This analysis revealed the presence of at least two regions of association with RA in the Class I region, independent of DRB1 genotype. SNP alleles found on the conserved A1-B8-DR3 (8.1) haplotype show the strongest evidence of positive association (P ~ 0.00005) clustered in the region around the HLA-C locus. In addition, we identified risk alleles that are not present on the 8.1 haplotype, with maximal association signals (P ~ 0.001–0.0027) located near the ZNF311 locus. This latter association is enriched in DRB1*0404 individuals. Finally, several additional association signals were found in the extreme centromeric portion of the MHC, in regions containing the DOB1, TAP2, DPB1, and COL11A2 genes. These data emphasize that further analysis of the MHC is likely to reveal genetic risk factors for rheumatoid arthritis that are independent of the DRB1 shared epitope alleles.
doi:10.2119/2007-00123.Lee
PMCID: PMC2255558  PMID: 18309376
12.  A comparison of founder-only and all-pedigree-members genotype-expression association by regression analysis 
BMC Proceedings  2007;1(Suppl 1):S8.
Genotype-expression association analysis using linear regression may produce different test results depending on whether founders only or all pedigreed members are used. This difference is not due to the correlation of samples within a pedigree, because linear mixed models have been applied to account for that correlation. We investigated the possibility that the difference is due to a dependence of expression levels on, among other things, the generation number in the pedigree. Indeed, of the 30 or so studied expression quantitative traits, several of them show significant dependence on the generation number. We propose to use all pedigree members in genotype-expression association analyses whenever the complete genotyping information is available.
PMCID: PMC2367500  PMID: 18466582
13.  Association of STAT4 with Rheumatoid Arthritis in the Korean Population 
Molecular Medicine  2007;13(9-10):455-460.
A recent study in the North American White population has documented the association of a common STAT4 haplotype (tagged by rs7574865) with risk for rheumatoid arthritis (RA) and systemic lupus erythematosus. To replicate this finding in the Korean population, we performed a case-control association study. We genotyped 67 single nucleotide polymorphisms (SNPs) within the STAT1 and STAT4 regions in 1123 Korean patients with RA and 1008 ethnicity-matched controls. The most significant four risk SNPs (rs11889341, rs7574865, rs8179673, and rs10181656 located within the third intron of STAT4) among 67 SNPs are identical with those in the North American study. All four SNPs have modest risk for RA susceptibility (odds ratio 1.21–1.27). A common haplotype defined by these markers (TTCG) carries significant risk for RA in Koreans [34 percent versus 28 percent, P = 0.0027, OR (95 percent CI) = 1.33 (1.10–1.60)]. By logistic regression analysis, this haplotype is an independent risk factor in addition to the classical shared epitope alleles at the HLA-DRB1 locus. There were no significant associations with age of disease onset, radiographic progression, or serologic status using either allelic or haplotypic analysis. Unlike several other risk genes for RA such as PTPN22, PADI4, and FCRL3, a haplotype of the STAT4 gene shows consistent association with RA susceptibility across Whites and Asians, suggesting that this risk haplotype predates the divergence of the major racial groups.
doi:10.2119/2007-00072.Lee
PMCID: PMC2014726  PMID: 17932559
14.  Eosinophilic Fasciitis Associated with Autoimmune Thyroiditis 
Eosinophilic fasciitis (EF) is scleroderma-like disease without Raynaud's phenomenon or visceral involvement. It is characterized by painful swelling of the extremities, accompanied by rapid weight gain, fever and myalgia. The acute state of disease is associated with significant peripheral blood eosinophilia, an elevated erythrocyte sedimentation rate and hypergammaglobulinemia. EF is also frequently associated with hematological abnormalities, including malignant lymphoproliferative diseases, but rarely associated with autoimmune thyroiditis. In the present study we report a case of eosinophilic fasciitis associated with autoimmune thyroiditis.
doi:10.3904/kjim.2005.20.2.180
PMCID: PMC3891391  PMID: 16134777
Fasciitis; Eosinophilia; Autoimmune thyroiditis
15.  Adult-onset Still's Disease with Disseminated Intravascular Coagulation and Multiple Organ Dysfunctions Dramatically Treated with Cyclosporine A 
Journal of Korean Medical Science  2004;19(1):137-141.
Severe systemic manifestations of adult onset Still's disease (AOSD) are often fatal and occasionally related to hemophagocytic syndrome (HS). We describe the case of a 49-yr-old woman with AOSD presenting with non-remitting high fever, confusion, jaundice, hepatosplenomegaly, serositis, azotemia, pancytopenia, coagulopathy with disseminated intravascular coagulation (DIC), hyperferritinemia, acute acalculous cholecystitis and ileocolitis noted in computed tomographic images. The patient had a history of herpes zoster developed prior to the admission, but there is no history of diarrhea or abdominal pain. Although bone marrow examination was not performed due to hemorrhagic diathesis, we suspected AOSD-associated HS on the basis of clinical course without detectable infectious agents in cultures or serologic studies. Intravenous immunoglobulin, pulse methylprednisolone, oral cyclosporine A (CsA) and ceftriaxone brought about transient improvement of fever and confusion, but the disease progressed. After increasing CsA dose, all previously mentioned abnormalities disappeared rapidly. Accordingly, we believe that DIC and multiple organ dysfunctions might have been the complications of HS but not that of sepsis, and that CsA can be used as a first-line therapy in case of life-threatening situations.
doi:10.3346/jkms.2004.19.1.137
PMCID: PMC2822251  PMID: 14966357
Still's Disease, Adult-onset; Hemophagocytic Syndrome; Cyclosporins
16.  A Korean rheumatic diseases screening questionnaire. 
Journal of Korean Medical Science  2003;18(2):171-178.
The aim of our study was to develop a Korean rheumatic diseases-screening questionnaire. The questionnaire was constructed based on American College of Rheumatology criteria for rheumatic diseases and a connective tissue diseases screening questionnaire. Two groups of patients were selected and completed the questionnaire: (i) those with osteoarthritis (n=46), rheumatoid arthritis (n=52), systemic lupus erythematosus (n=50), scleroderma (n=8), polymyositis or dermatomyositis (n=7), Sjogren's disease (n=4), and mixed connective-tissue disease (n=9) as case subjects; and (ii) those with fibromyalgia (n=8) and general disease without evidence of any rheumatic disease (n=72) as controls. Laboratory results were analyzed for correlation with actual data using kappa (kappa) statistics. Test-retest reliability was performed in 12 patients, and showed strong agreement between the first and second interviews (kappa=0.91). The sensitivity of the questionnaire ranged from 77.8 to 100%, and specificity ranged from 68.8 to 95.0%. Negative predictive values were very high in the general population, from 98.4 to 99.99%. The kappa statistic for agreement between laboratory items was 0.22-0.56, except for rheumatoid factor, antinuclear antibody test, and muscle enzyme level. We have developed a simple and sensitive Korean rheumatic diseases-screening questionnaire for the epidemiologic study of rheumatic diseases in Korea.
PMCID: PMC3055029  PMID: 12692412
17.  Undifferentiated spondyloarthropathy in Korea: focusing on peripheral arthritis. 
Undifferentiated spondyloarthropathy (USpA) includes the forms that do not meet criteria for the established categories of spondyloarthropathy. The clinical spectrum of USpA is therefore wide and few studies have been published on USpA, especially peripheral arthritis. A total of 107 patients fulfilling the European Spondyloarthropathy Study Group criteria for SpA were studied retrospectively by a chart review and interview by a rheumatologist. Peripheral arthritis, excluding hip and shoulder involvement, occurred in 97 of the 107 patients (91%). Joint involvement tended to be monoarticular or pauciarticular, and most frequently developed in peripheral joints including the knee and ankle. Among the 97 patients with peripheral arthritis, only 37 (35%) had a persistent arthritis. HLA-B27 was detected in 80 patients (78%). Peripheral arthritis was found in the lower extremities regardless of symmetry or asymmetry and tended to run a benign course with only a few patients having persistent arthritis.
PMCID: PMC3054814  PMID: 11850592
18.  Association Between FcgammaR IIa and IIIa polymorphism and clinical manifestations in Korean patients with adult-onset Still's disease. 
High-dose intravenous immunoglobulins alter the disease activity of adult-onset Still's disease (AOSD). Because activation status of FcgammaR is possibly dependent on their genetic polymorphisms, we investigated whether the polymorphisms of FcgammaR IIa and IIIa are risk factors, and affect the clinical features of AOSD. Genomic DNA was extracted from 36 patients and from 197 healthy controls. Polymerase chain reaction for FcgammaR IIa and IIIa using the allele-specific primers and direct sequencing of FcgammaR IIIa polymorphic site were performed. The frequencies of FcgammaR IIa/IIIa genotype between patients with AOSD and controls were not different. The allelic frequencies of FcgammaR IIa/IIIa between patients with AOSD and controls were not different, either. However, the FcgammaR IIa-R/R131 genotype was associated with a higher concentration of hemoglobin (p=0.04) and stable liver function (p=0.009) than the other genotypes. The FcgammaR IIIa-F/F176 genotype was associated with significantly lower titers of serum ferritin (p=0.025), and higher serum albumin (p=0.037) and cholesterol (p=0.014) concentrations than the other genotypes. This study suggest that the FcgammaR IIa and IIIa polymorphisms might not be genetic risk factors for AOSD in Korean, but contribute to the activity of disease. FcgammaR IIa-R/R131 and IIIa-F/F176 genotypes, low-binding genotypes for IgG2a and G1, may have more protective effects in acute stage of the disease than the other genotypes.
PMCID: PMC3054835  PMID: 11850593

Results 1-18 (18)