Churl Hyun Im

T-cell immunoglobulin and mucin domain 3 genetic polymorphisms are associated with rheumatoid arthritis independent of a shared epitope status.

The aim of this study was to investigate T-cell immunoglobulin and mucin domain 3 (TIM3) genetic polymorphisms and rheumatoid arthritis (RA) according to the shared epitope (SE) status. Six single nucleotide polymorphisms (SNPs: rs11742259 [C/T], rs10515746 [C/A], rs35960726 [A/G], rs1036199 [A/C], rs4704846 [A/G], and rs11134551 [A/G]) in the TIM3 gene from 366 RA patients and 389 healthy controls were investigated using the real-time polymerase chain reaction method. Associations between these SNPs and clinical manifestations (including SE status) were investigated using the SPSS program and Haploview. Polymorphisms of rs35690726 (AG+ GG vs AA: 8.2% vs 1.8%, p(c) < 0.001) were significantly associated with RA with or without SE (p(c) < 0.001 or p(c) = 0.009, respectively). Polymorphisms of rs11742259 (p(c) = 0.003) and rs1036199 (p(c) = 0.012) were significantly different in RA patients with SE, but not in those without SE. In haplotype analysis with a permutation test for the first 4 SNPs (rs11742259, rs10515746, rs35690726, and, rs1036199), CCAA, CCGA, CCGC, and CAAA haplotypes were significantly associated with RA. The clinical characteristics of RA patients were not significantly associated with any TIM3 polymorphism. TIM3 genetic polymorphisms may have a role in the development of RA regardless of a shared epitope status.

A case of hypertrophic osteoarthropathy associated with epithelioid hemangioendothelioma.

Epithelioid hemangioendothelioma is a rare vascular tumor, which occurs in the lung, liver, bone, and soft tissue. Hypertrophic osteoarthropathy is a syndrome characterized by subperiosteal new bone formation, joint effusion and clubbing, and may be associated with cyanotic heart disease, chronic pulmonary disease, liver disease, and other miscellaneous diseases. The activation of endothelium and platelets has been suggested to be involved in the development of hypertrophic osteoarthropathy. We report a rare case of hypertrophic osteoarthropathy, which developed in association with hepatic epithelioid hemangioendothelioma with pulmonary metastasis. We also discuss the role of vascular endothelial growth factor in its pathogenesis.

Matrix metalloproteinase–9 promoter polymorphisms in Korean patients with systemic lupus erythematosus

To investigate the association between functional promoter polymorphisms of matrix metalloproteinase-9 (MMP-9) and systemic lupus erythematosus (SLE), we analyzed MMP-9 promoter -1562 C>T and MMP-9 -90 (CA)(n) repeat polymorphisms in 135 Korean SLE patients (mean age, 34.7 years; 124 female and 11 male) and in 135 gender- and age-matched healthy controls (mean age, 35.4 years). Clinical and laboratory findings were collected during the follow-up period (mean, 63.5 months; range, 3-252 months), and Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Indexes were calculated. The levels of total MMP-9 were measured in sera of SLE patients and controls by enzyme-linked immunoabsorbent assay. The serum levels of MMP-9 in SLE patients were significantly lower than those of controls (mean +/- standard error of the mean, 1421.6+/-177.4 vs 3731.4+/-441.4 ng/ml, p=1.2 x 10(-5) by t test). Both functional polymorphisms were under the Hardy-Weinberg equilibrium state except (CA)(n) repeat polymorphisms in SLE patients (p=2.6 x 10(-5) by chi(2) goodness-of-fit test). The distribution of the MMP-9 promoter polymorphisms or haplotypes was not significantly different in SLE patients and controls. However the frequency of alleles with low numbers of CA repeats (n<21, 11.9% vs 7.0%, p=0.06 by the chi(2) test; odds ratio=1.78, 95% confidence interval=0.99-3.20) and the prevalence of low CA repeats homozygote tended to be higher in patients than in controls (5.2% vs 0.7%, p=0.07 by logistic regression, odds ratio=7.29, 95% confidence interval=0.88-60.10) in the recessive model. No relationship was found between MMP-9 polymorphisms and clinical features or damage as indicated by SLICC/ACR Damage Index in the study subjects. These results suggest that genetic polymorphisms of the MMP-9 promoter regions are not associated with the development of SLE in Korea.

CXCR3 polymorphism is associated with male gender and pleuritis in patients with systemic lupus erythematosus.

BACKGROUND Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease involving multiple organs. Chemokines and their receptors play an important role in the pathogenesis of SLE. Lymphocytes expressing CXCR3, chemokine receptors of CXCL4, 9, 10, and 11, increase in patients with SLE and animal models, particularly in those with skin manifestations and nephritis. We investigated CXCR3 genetic polymorphisms in patients with SLE and their association with clinical manifestations. METHODS A total of 346 patients with SLE and 540 healthy controls were investigated for CXCR3 intron 1 polymorphisms rs2280964 and rs34334103 by Taqman analysis. RESULTS rs2280964 and rs34334103 were not associated with all patients with SLE, but rs34334103 showed a significant association with male patients with SLE. Among the clinical manifestations, pleuritis was associated with the rs34334103 polymorphism. CONCLUSION The CXCR3 polymorphism rs34334103 was associated with male gender and pleuritis in patients with SLE.

A Case of Renal Crisis in a Korean Scleroderma Patient with Anti-RNA polymerase I and III Antibodies

Scleroderma (SSc) renal crisis has been reported to be associated with anti-RNA polymerase I and III (RNAP I/III) antibodies in Caucasians and the Japanese. However, no report is available for Korean SSc patients. Here, we describe the case of a 65-yr-old female SSc patient who developed renal crisis and whose serum contained anti-RNAP I/III antibodies. She was finally diagnosed as having diffuse cutaneous SSc based on skin thickening proximal to the elbows and knees. Sudden hypertension, oliguria, and pulmonary edema were features of her renal crisis. Despite the use of captopril and adequate blood pressure control, her renal function deteriorated. Subsequent renal biopsy findings showed severe fibrinoid necrosis with luminal obliteration in interlobar arteries and arterioles consistent with SSc renal crisis. Serum anti-RNAP I/III antibodies were detected by radioimmunoprecipitation. This is the first report of a renal crisis in a Korean SSc patient with RNAP I/III antibodies.

Complex repetitive discharge on electromyography as a risk factor for malignancy in idiopathic inflammatory myopathy

Background/Aims We investigated the electromyography (EMG) findings and demographic, clinical, and laboratory features that may predict the development of malignancy in patients with idiopathic inflammatory myopathy (IIM). Methods In total, 61 patients, 36 with dermatomyositis and 25 with polymyositis, were included. Patients were divided into those with and without malignancies, and comparisons were made between the groups in terms of their demographic, clinical, laboratory, and EMG findings. Results The frequencies of malignancies associated with dermatomyositis and polymyositis were 22% and 8%, respectively. Patients with malignancies showed a significantly higher incidence of dysphagia (odds ratio [OR], 21.50; 95% confidence interval [CI], 3.84 to 120.49), absence of interstitial lung disease (ILD; OR, 0.12; 95% CI, 0.01 to 0.98), and complex repetitive discharge (CRD) on the EMG (OR, 26.25; 95% CI, 2.67 to 258.52), versus those without. After adjustment for age, dysphagia and CRD remained significant, while ILD showed a trend for a difference but was not statistically significant. Multivariate analysis revealed that the CRD conferred an OR of 25.99 (95% CI, 1.27 to 531.86) for malignancy. When the frequency of malignancy was analyzed according to the number of risk factors, patients with three risk factors showed a significantly higher incidence of malignancy, versus those with fewer than two (p = 0.014). Conclusions We demonstrated for the first time that CRD on the EMG was an additional independent risk factor for malignancy in IIM. Further studies on a larger scale are needed to confirm the importance of CRD as a risk factor for malignancy in IIM.