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Lee, Kyung-Eun,Kang, Ji-Hyoun,Yim, Yi-Rang,Kim, Ji-Eun,Lee, Jeong-Won,Wen, Lihui,Park, Dong-Jin,Kim, Tae-Jong,Park, Yong-Wook,Yoon, Kyung Chul,Lee, Ji Shin,Lee, Shin-Seok The Korean Academy of Medical Sciences 2016 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.31 No.2
<P>We investigated the clinical and biological significance of germinal centers (GC) present in the minor salivary glands of patients with Sjögren’s syndrome (SS). Minor salivary gland tissue biopsies from 93 patients with SS were used to identify GC-like structures, which were confirmed by CD21-positive follicular dendritic cell networks. Patients were compared based upon sociodemographics, glandular and extraglandular manifestations, and laboratory findings including autoantibody profiles, complement, and immunoglobulin levels; EULAR SS disease activity index (ESSDAI) and SS disease damage index (SSDDI) were also measured. GC-like structures were observed in 28 of 93 SS patients (30.1%). Mean focus scores and CRP levels were significantly higher in GC-positive patients than in GC-negative patients; GC-positive patients also exhibit a higher prevalence of rheumatoid factor and anti-SS-A/Ro antibodies compared to GC-negative patients. No differences in glandular or extra-glandular manifestations were evident between groups. In conclusion, SS patients with GC-like structures in the minor salivary glands exhibited laboratory profiles significantly different from those of their GC-negative counterparts. Long-term follow-up of these patients will be necessary to determine whether these laboratory abnormalities are predictive of clinical outcomes.</P>
( Jae Yeong Cho ),( Kye Hun Kim ),( Kyung Jin Lee ),( Yi Rang Yim ),( Sung Soo Kim ),( Hae Chang Jeong ),( Ki Hong Lee ),( Keun Ho Park ),( Doo Sun Sim ),( Hyun Ju Yoon ),( Nam Sik Yun ),( Young Joon 대한내과학회 2014 대한내과학회 추계학술발표논문집 Vol.2014 No.1
Background:Since severe tricuspid regurgitation (TR) is an uncommon fi nding which develops in various conditions, the present study aimed to investigate etiology, clinical characteristics, and predictors of reversibility in patients with severe TR. Methods:A total of 232 patients (67. 4±14. 1 years, 80 males) who were diagnosed with severe TR by echocardiography were enrolled. Severe TR was defi ned as vena contracta width greater than 0. 7 cm and systolic fi ow reversal in hepatic veins according to the current guideline of American Society of Echocardiography (ASE). Improvement of TR to moderate or less degree on follow up echocardiography was considered as reversible TR in the present study. Primary end points were adverse events at long-term follow-up. Adverse events were defi ned as all-cause death and operation due to severe TR. Results: Reversible TR was observed in 35 out of 153 patients (23. 0%). Sixty-one patients showed clinical improvement, but the degree of TR was not changed. Forty-nine patients (32%) who did not show clinical improvement despite of medical therapy eventually underwent surgical correction of TR, and 7 patients died. In addition, 17 patients died without operation, so 24 deaths (16%) were observed in total. finally, total adverse events developed in 66 patients (41%) during 2 years of follow-up period. Logistic regression analysis revealed prosthetic mitral valve was the only independent predictors of future adverse events (OR 2. 47, 95%CI 1. 05-5. 77, p=0. 038). Independent predictors of improved TR turned out to be the use of RAAS blockade (HR 3. 02, 95%CI 1. 12-8. 17, p=0. 030) and the use of spironolactone (HR 3. 39, 95%CI 1. 05-10. 90, p=0. 041). Low ejection fraction (LVEF <50%) also had a trend toward the reversibility (HR 2. 82, 95%CI 0. 94-8. 40). Conclusions:Considering results above, reversible severe TR mainly associated with left heart failure and medical treatment should be given before considering surgery for severe TR.
A Case of Sarcoidosis That Improved upon Discontinuation of Etanercept
( Ji Hyoun Kang ),( Joon Ho Ahn ),( Ji Eun Yu ),( Ji Eun Kim ),( Yi Rang Yim ),( Jeong Won Lee ),( Kyung Eun Lee ),( Dong Jin Park ),( Lihui Wen ),( Yong Wook Park ),( Shin Seok Lee ) 대한류마티스학회 2016 대한류마티스학회지 Vol.23 No.3
A 31-year-old man who had been prescribed etanercept over a 3-year period for treatment of ankylosing spondylitis presented with newly developed dry cough, chills, myalgia, and weight loss. Chest computed tomography showed multiple reticulonodular pulmonary infiltrates and bilateral mediastinal, hilar, and peribronchial lymphadenopathy. Biopsy of a paratracheal lymph node revealed chronic granulomatous inflammation without necrosis, and the serum angiotensin-converting enzyme level was elevated. Sarcoidosis was diagnosed. His laboratory and radiological findings, and clinical symptoms improved only after discontinuation of etanercept without treatment. Although etanercept-induced sarcoidosis is rare, this case report suggests that sarcoidosis should be considered in the differential diagnosis of patients treated with the tumor necrosis factor inhibitor. (J Rheum Dis 2016;23:187-192)
( Kyung-eun Lee ),( Dong-jin Park ),( Sung-eun Choi ),( Ji-hyoun Kang ),( Yi-rang Yim ),( Ji-eun Kim ),( Jeong-won Lee ),( Lihui Wen ),( Tae-jong Kim ),( Yong-wook Park ),( Ji Shin Lee ),( Kyung Chul 대한류마티스학회 2016 대한류마티스학회지 Vol.23 No.5
Objective. To evaluate the laboratory and clinical manifestations of Sjogren`s syndrome (SS) association with chemokine (C-X-C motif) ligand 1 (CXCL1) expression in the ductal and acinar salivary gland epithelial cells (SGEC) of the minor salivary glands. Methods. The sociodemographic data of 106 SS patients was obtained, and the glandular and extraglandular manifestations of the disease documented. The minor salivary glands were biopsied and the laboratory findings analyzed. European League Against Rheumatism SS disease activity index (ESSDAI) and SS disease damage index (SSDDI) scores were obtained during biopsy. An immunohistochemical approach was used to define the expression of CXCL1 in the salivary glands. Results. Of 106 patients, the minor salivary glands of 22 patients (20.7%) stained positively for CXCL1. Such CXCL1-positive patients exhibited higher ESSDAI scores at the time of biopsy than the CXCL1-negative patients (3.86±2.27 vs. 2.64±1.62, p=0.015). Lymphadenopathy was more frequently observed in CXCL1-positive patients, compared with CXCL1-negative patients (31.8% vs. 9.5%, p=0.014). No differences between groups were identified in terms of sociodemographic characteristics, laboratory data, or the extent of the glandular manifestation of SS. Conclusion. The expression of CXCL1 within the ductal and acinar SGEC of SS patients is associated with lymphadenopathy and elevated clinical disease activity. CXCL1 may play an important role in the disease activity and prognosis of SS. (J Rheum Dis 2016;23:297-303)
영구형 심박동기 삽입 후 유의한 삼첨판 역류증 발생의 예측인자
이경진 ( Kyoung Jin Lee ),김계훈 ( Kye Hun Kim ),임이랑 ( Yi Rang Yim ),박혁진 ( Hyuk Jin Park ),이승헌 ( Seung Hun Lee ),김지은 ( Ji Eun Kim ),정형기 ( Hyung Ki Jeong ),윤현주 ( Hyun Ju Yoon ),윤남식 ( Nam Sik Yoon ),홍영준 ( You 대한내과학회 2014 대한내과학회지 Vol.86 No.5
Background/Aims: We sought to identify predictors of significant tricuspid regurgitation (TR) after successful permanent pacemaker (PPM) implantation in Korean patients. Methods: Of 404 patients who underwent PPM implantation, 187 patients who had both baseline and follow-up echocardiographic examinations were assigned to one of two groups: no development or change in TR (Group I, n = 172, 65.5 ± 13.7 years) versus the development of significant TR (Group II, n = 15, 72.1 ± 8.3 years). Clinical, laboratory, and echocardiographic variables were compared between the two groups. Results: Overall, the grade of TR was significantly aggravated from 0.46 ± 0.73 to 0.81 ± 0.84 (p < 0.001) during 3.1 ± 1.8 years of follow-up (0.49 ± 0.75 to 0.69 ± 0.74 in Group I, p < 0.001; 0.13 ± 0.35 to 2.27 ± 0.46 in Group II, p < 0.001). The de novo development or aggravation of TR was observed in 66 patients (35.3%), and significant TR developed in 15 patients (8.0%). The presence of atrial fibrillation (AF) was significantly higher (53.3 vs. 18.6%, p = 0.002), and the implantation of a ventricle pacing, ventricle sensing, inhibited by ventricular event (VVI) type pacemaker was more frequent in Group II than in Group I (46.7 vs. 15.1%, p = 0.002). Other variables were not different between the groups. Conclusions: The development or aggravation of TR was not rare after successful PPM implantation, even though the development of significant TR was uncommon. The presence of AF and the implantation of a VVI type pacemaker were predictors of the development of significant TR. Together, the results of this study suggest that the development or aggravation of TR should be monitored carefully after PPM implantation. (Korean J Med 2014;86:577-584)
( Dong Jin Park ),( Shin Seok Lee ),( Ji Hyoun Kang ),( Jung Ho Choi ),( Yi Rang Yim ),( Jeong Won Lee ),( Kyung Eun Lee ),( Li Hui Wen ),( Tae Jong Kim ),( Yong Wook Park ),( Yukitoshi Takahashi ) 대한내과학회 2014 대한내과학회 추계학술발표논문집 Vol.2014 No.1
Background: The high concordance of systemic lupus erythematosus (SLE) with fi bromyalgia (FM) suggests common underlying mechanisms related to pain and distress in both patient groups. This study was aimed to evaluate roles of NMDAR antibodies in development of FM in SLE patients Methods: Sera from 104 SLE patients, 112 FM patients, and 110 healthy controls were analyzed to detect titers of antibodies to N-terminus of 2B subunit of NMDAR (GluN2B). Clinical, laboratory data and concomitant diseases were found by reviewingthe patient charts. We underwent clinical examination and neuropsychiatric evaluation, and interviewed SLE patients using a structured questionnaire that included FM and neuropsychiatric symptoms. Results: 18 patients (17. 3 %) of total 104 SLE patients were revealed having FM. The titer of anti-GluN2B antibodies was signifi cantly higher in SLE patients than FM patients and healthy controls (P < 0. 001). In SLE patients, patients with concomitant FM showed higher titers of anti-GluN2B antibodies (P < 0. 05). The titers of anti-GluN2B antibodies were correlated with tender point count (Spearman`s rho = 0. 238, P = 0. 016) and widespread pain index (Spearman`s rho = 0. 276, P = 0. 005), but not with other symptom scales. Anti-GluN2B antibody-positive SLE patients were more likely to have NPSLE and concomitant FM (P < 0. 05). In multivariate analysis, Anti-GluN2B antibody was independent predictor of concomitant FM and NPSLE. Conclusions: This is the fi rst study to present that antibodies to NMDAR may be associated with pathogenesis of FM in SLE patients.
( Kyung Eun Lee ),( Dong Jin Park ),( Jeong Won Lee ),( Ji Hyoun Kang ),( Jung Ho Choi ),( Yi Rang Yim ),( Li Hui Wen ),( Tae Jong Kim ),( Yong Wook Park ),( Shin Seok Lee ) 대한내과학회 2014 대한내과학회 추계학술발표논문집 Vol.2014 No.1
Background: In the current study, we investigated whether the laboratory and clinical manifestations of SS patients were associated with CCL21 and CXCL13 expression levels in the minor salivary gland. Methods: We obtained sociodemographic data on a total of 106 SS patients, documented glandular and extraglandular manifestations of the disease, performed minor salivary gland biopsies, and analyzed laboratory fi ndings. EULAR index values of SS disease activity (ESSDAI values) at the time of biopsy, and SS disease damage index (SSDDI) values, were also noted. An immunohistochemical approach was used to (semiquantitatively) measure the expression levels of CCL21 and CXCL13 in the minor salivary glands. Results: The minor salivary glands of SS patients stained positively for CCL21 and CXCL13 in 46. 2% (49/106) and 70. 7% (75/106) of all cases, respectively. Increased expression of CCL21 was associated with an elevated ESR, an increased IgG level, elevated anti-SS-A and -SS-B titers, a higher focus score, and a greater ESSDAI value atthe time of biopsy. Increased expression of CXCL13 was associated with an decreased WBC, reduced lymphocyte, low platelet, elevated ESR, an increased IgG level, elevated anti-SS-A and -SS-B titers, a rise in the level of rheumatoid factor, a higher focusscore, and a greater ESSDAI value at the time of biopsy. In patients with extraglandular manifestations of SS, the prevalence of lymphadenopathy tended to rise with an increase in the level of CCL21. Conclusions:The expression levels of CCL21 and CXCL13 within the lymphocytic infi ltratesof SS patients were associated with several laboratory features of the disease, lymphadenopathy, and the extent of clinical disease activity. CCL21 and CXCL13 levels should serve as useful markers predicting SS disease activity and prognosis.
( Ki Jeong Park ),( Young Nan Cho ),( Hye Mi Jin ),( Kyung Eun Lee ),( Jeong Won Lee ),( Jeong Hwa Kang ),( Hyun Ju Jung ),( Yi Rang Yim ),( Jung Ho Choi ),( Dong Jin Park ),( Sung Ji Lee ),( Tae Jong 대한내과학회 2014 대한내과학회 추계학술발표논문집 Vol.2014 No.1
Background: Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections and play an important role in mucosal immunity. However, the role of MAIT cells remains enigmatic in autoimmune diseases. Here, we examined the level and function of MAIT cells in patients with rheumatic diseases. Methods: Patients with systemic lupus erythematosus (SLE; n = 54), rheumatoid arthritis (RA; n = 66), Behcet`s disease (n = 9), ankylosing spondylitis (n = 21), and healthy controls (n = 136) were enrolled in the study. MAIT cell, cytokine and programmed death-1 (PD-1) levels were measured by fiow cytometry. Results: Circulating MAIT cell levels were significantly reduced in SLE and RA patients. In particular, this MAIT cell deficiency was more prominent in CD8+ and double-negative T cell subsets, and significantly correlated with disease activity, such as SLE disease activity index (SLEDAI) and 28-joint disease activity score (DAS28). Interestingly, MAIT cell frequency was significantly correlated with natural killer T (NKT) cell frequency in SLE patients. IFN-γ production in MAIT cells was impaired in SLE patients, which was due to an intrinsic defect in the Ca2+/calcineurin/NFAT1 signaling pathway. In SLE patients, MAIT cells were poorly activated by a-galactosylceramide- stimulated NKT cells, thereby showing the dysfunction between MAIT cells and NKT cells. Notably, an elevated expression of PD-1 in MAIT cells and NKT cells was associated with SLE. In RA patients, MAIT cell levels were significantly higher in synovial fiuid than in peripheral blood. Conclusions: Our study primarily demonstrates that MAIT cells are numerically and functionally deficient in SLE. In addition, we report a novel finding that this MAIT cell deficiency is associated with NKT cell deficiency and elevated PD-1 expression. These abnormalities possibly contribute to dysregulated mucosal immunity in SLE.
( Ki Jeong Park ),( Hye Mi Jin ),( Young Nan Cho ),( Jeong Hwa Kang ),( Hyun Ju Jung ),( Ji Hyoun Kang ),( Ji Eun Kim ),( Yi Rang Yim ),( Jeong Won Lee ),( Kyung Eun Lee ),( Dong Jin Park ),( Tae Jong 대한류마티스학회 2016 대한류마티스학회지 Vol.23 No.1
Objective. The purpose of this study is to evaluate the clinical and hematological effects of tocilizumab in active rheumatoid arthritis (RA) patients. Methods. Fourteen patients with active RA were enrolled in this study. The patients received tocilizumab 8 mg/kg intravenously every four weeks for 6 months. Disease activity, anemia-related factors including serum hepcidin-25, and hematological parameters were monitored at baseline and at 1, 3, and 6 months after the initiation of treatment. Results. Significant reductions in tender joint count, swollen joint count, visual analogue scale, erythrocyte sedimentation rate (ESR), and C-reactive (CRP) protein plus reductions in a 28-joint disease activity score were observed within one month after the first tocilizumab treatment. These effects lasted throughout the six-month study period. In addition, significant improvements in anemia-related factors such as hepcidin-25, ferritin, iron, hemoglobin, red blood cell counts and mean corpuscular volume were observed during the treatment period. Hematological parameters were improved with reductions in counts for leukocytes, monocytes, neutrophils, and platelets. The lymphocyte counts and their subset numbers were unchanged. Changes in hepcidin levels showed significant correlation with changes in CRP, ESR, ferritin, hemoglobin and counts for red blood cells, leukocytes, and neutrophils during the treatment period. Conclusion. This study demonstrates that tocilizumab significantly and meaningfully reduces disease burden in patients with active RA. In addition, tocilizumab diminishes the levels of inflammatory anemia by inhibiting hepcidin production. These clinical data provide evidence of a favorable outcome from tocilizumab in RA. (J Rheum Dis 2016;23:37-46)