건성안 환자에서 쇼그렌증후군의 빈도 및 임상양상

이준성,최원,이신석,윤경철.Jun Sung Lee. MD. Won Choi. MD. Shin Seok Lee. MD. Kyung Chul Yoon. MD. PhD 대한안과학회 2012 대한안과학회지 Vol.53 No.4

Purpose: To investigate the prevalence and clinical aspects of Sjögren syndrome in patients who were diagnosed with dry eye syndrome in Korea. Methods: The medical records of patients who were diagnosed with dry eye syndrome in a dry eye clinic during a 2-year period (March 2008 to March 2010) and were followed up for more than 3 months were reviewed retrospectively. Results: A total of 206 patients were included in the present study. Fifty-eight patients (28%) had Sjögren syndrome and 39 patients (19%) showed primary Sjögren syndrome. Sjögren syndrome patients showed poorer results than non-Sjögren syndrome patients in ocular surface disease index score (OSDI), tear break up time, Schirmer test score, and ocular surface staining score using the Oxford scheme (p < 0.05). Among the patients with primary Sjögren syndrome, 27 patients were SSA (anti-Ro antibodies) or SSB (anti-La antibodies) positive and 12 patients were sero-negative. There were no statistically significant differences in objective or subjective parameters between the sero-positive and sero-negative groups. Conclusions: Sjögren syndrome was observed in 28% of all dry eye patients, in two-thirds of severe dry eye patients. Sjögren syndrome patients showed more severe clinical aspects than dry eye patients with non-Sjögren syndrome. Diagnosing Sjögren syndrome through systemic evaluation is necessary in the patients with severe dry eye. J Korean Ophthalmol Soc 2012;53(4):499-504

Disruption of endothelial barrier function is linked with hyposecretion and lymphocytic infiltration in salivary glands of Sjögren's syndrome

Cong, Xin,Zhang, Xue-Ming,Zhang, Yan,Wei, Tai,He, Qi-Hua,Zhang, Li-Wei,Hua, Hong,Lee, Sang-Woo,Park, Kyungpyo,Yu, Guang-Yan,Wu, Li-Ling Elsevier 2018 Biochimica et biophysica acta. Molecular basis of Vol.1864 No.10

<P><B>Abstract</B></P> <P>Sjögren's syndrome (SS) is an inflammatory autoimmune disease that causes hyposecretion in salivary glands. Endothelial tight junctions (TJs) play crucial roles in salivation and barrier function of blood vessels. However, whether the alteration of endothelial TJs were involved in pathogenesis of SS was still unknown. Here, the ultrastructure and function of endothelial TJs in submandibular glands (SMGs) were detected by transmission electron microscopy and in vivo paracellular permeability assay in different aged NOD mouse model for SS. CFSE-labeled lymphocytes were injected into tail vein to trace the infiltration, while claudin-5 expression and distribution were detected by immunofluorescence, qRT-PCR, and western blot. Results showed that the stimulated salivary flow rate was gradually decreased and lymphocytic infiltration was found as age increased in 12- and 21-week-old NOD mice, but not 7-week-old NOD mice. Blood vessels were dilated, while endothelial TJ width and paracellular tracer transport were increased in 12-week-old NOD mice. Moreover, the injected CFSE-labeled lymphocytes were observed in SMGs of 12-week-old NOD mice. Claudin-5 level was increased and relocalized from the apical portion of neighboring endothelial cells to lateral membranes and cytoplasm in 12-week-old NOD mice. Additionally, the alteration of claudin-5 expression and distribution was further confirmed in labial salivary glands and bilateral parotid glands from SS patients. In cultured human microvessel endothelial cell line (HMEC-1), IFN-γ stimulation significantly increased claudin-5 expression. Taken together, we identified that the endothelial TJ barrier was disrupted and contributed to the development of salivary hyposecretion and lymphocytic infiltration in SS.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Endothelial tight junction barrier is disrupted in hyposecretory submandibular glands from Sjögren's syndrome mouse model </LI> <LI> The disrupted salivary endothelial barrier is linked with lymphocytic infiltration in Sjögren's syndrome mouse model </LI> <LI> The redistribution of claudin-5 is responsible for disrupted endothelial barrier in salivary glands from Sjögren's syndrome </LI> </UL> </P>

노인 환자에서 쇠그렌증후군에 동반된 다발성 뇌경색증

김명국(Meyung-Kug Kim),유봉구(Bong-Goo Yoo) 대한임상노인의학회 2011 대한임상노인의학회지 Vol.12 No.4

Sjögren’s syndrome is an autoimmune disorder characterized by mononuclear infiltration and destruction of lacrimal gland and salivary gland resulting in xerostomia and xerophthalmia. Central nervous system involvements occur in 2∼25% of patients. A 77-year-old woman developed sudden onset of dysarthria and right hemiparesis. She had no risk factors for cerebral infarction. Diffusion weighted image showed multiple acute cerebral infarctions in left cerebral hemisphere. We treated with steroid and antiplatelet agent then her neurologic symptoms were improved. We report a old aged primary Sjögren’s syndrome patient with multiple cerebral infarction. 쇠그렌증후군은 단핵구가 외분비샘을 침범하여 눈마름증, 입안마름증 등의 증상을 나타내는 자가면역질환이다. 여러 장기를 침범할 수 있으며 2∼25%에서는 중추신경계 증상을 보인다. 77세 여자가 갑자기 발생한 조음장애와 오른쪽 팔과 다리의 위약을 주소로 내원하였다. 심뇌혈관질환의 위험 요인은 없었고, 확산강조영상에서 좌측 뇌에 다발성 급성 뇌경색이 관찰되었다. 쇠그렌증후군과 관련된 뇌경색증을 의심하여 스테로이드 및 항혈소판제를 투여하였으며 증상은 호전을 보였다. 쇠그렌증후군과 같은 결체조직 질환이 있는 경우에 이들 질환이 뇌경색증 발생에 영향을 줄 수 있음을 반드시 고려해 보아야 할 것이다.

Correlation between Tear Osmolarity and Other Ocular Surface Parameters in Primary Sjögren’s Syndrome

Mirinae Kim,Hyun Seung Kim,Kyung-Sun Na 대한안과학회 2017 Korean Journal of Ophthalmology Vol.31 No.1

Purpose: To investigate the relationships between tear osmolarity and other ocular surface parameters and to determine the diagnostic value of tear osmolarity in primary Sjögren’s syndrome (SS) using tear film break-up time, Schirmer I test, and cornea/conjunctiva staining. Methods: We included 310 eyes of 155 patients diagnosed with dry eye disease (39 primary SS and 116 non- Sjögren dry eye disease) at Seoul St. Mary’s Hospital from August 2010 to January 2015. All subjects completed the Ocular Surface Disease Index (OSDI) questionnaire and underwent ocular examinations including tear osmolarity (TearLab Osmolarity System), Schirmer I test, slit lamp examination for tear film break-up time, and corneal and conjunctival fluorescein staining. We used the mean value of both eyes for all parameters. Fluorescein staining was assessed using the Sjögren’s International Collaborative Clinical Alliance ocular staining score (OSS). Results: In primary SS patients (n = 39), the mean subject age was 52.5 ± 11.9 years, and 94.9% of the subjects were women. Mean tear osmolarity in SS was 311.1 ± 16.4 mOsm/L, with 16 (41.0%) subjects having values ≥316 mOsm/L. In SS, there was a positive correlation between mean tear osmolarity and OSDI score (ρ = 0.405, p = 0.011) and OSS (ρ = 0.592, p < 0.001). There was a negative correlation between mean tear osmolarity and the Schirmer I test (ρ = –0.625, p < 0.001). There was no significant correlation between mean tear osmolarity and tear film break-up time in SS (ρ = 0.110, p = 0.505). Conclusions: Tear osmolarity measurements using the TearLab Osmolarity System can reflect both symptom severity (OSDI) and objective signs (Schirmer test and OSS) in SS.

건성안 환자의 눈물 내 케모카인 리간드 5의 농도 분석

최원,이승현,윤경철,Won Choi,Seung-Hyun Lee,Kyung-Chul Yoon 대한안과학회 2011 대한안과학회지 Vol.52 No.6

Purpose: To investigate the expression of CCL5/RANTES (regulated upon activation, normal T cell expressed and secreted) in the tears of dry eye patients. Methods: Forty patients with dry eye (15 Sjögren’s and 25 non-Sjögren’s syndrome patients) and ten control subjects were recruited for the present study. The concentration of RANTES in tears was measured using an enzyme-linked immunosorbent assay. The correlations between RANTES level, tear film and ocular surface parameters, including tear film break-up time, basal tear secretion, tear clearance rate, corneal sensation, keratoepitheliopathy, and conjunctival goblet cell density, were analyzed in patients with dry eye syndrome. Results: The concentrations of RANTES were 435.46 ± 104.45 pg/ml in Sjögren’s syndrome patients, 257.42 ± 46.72 pg/ml in non-Sjögren’s syndrome patients, and 97.53 ± 29.15 pg/ml in the control patients (p < 0.01). The levels correlated significantly with basal tear secretion, tear clearance rate, keratoepitheliopathy, and goblet cell density (p < 0.05). Conclusions: CCL5/RANTES level increases in the tears of dry eye patients and correlates with various tear film and ocular surface parameters. J Korean Ophthalmol Soc 2011;52(6):658-664

일차성 쇼그렌 증후군 환자에서 발생한 눈물샘의 점막연관 림프조직형 림프종 1예

김효원(Hyo Won Kim),성윤미(Yoon Mi Sung),백지선(Ji Sun Baik),양석우(Suk Woo Yang) 대한안과학회 2016 대한안과학회지 Vol.57 No.7

목적: 일차성 쇼그렌 증후군과 베체트병을 동시에 진단 받은 환자에서 발생한 눈물샘의 점막연관 림프조직형 림프종을 항암화학요법을 통해 효과적으로 치료하였기에 이를 보고하고자 한다. 증례요약: 8년 전 쇼그렌 증후군과 베체트병을 진단 받은 49세 여자 환자가 1년 전부터 발생한 우안 위, 아래 눈꺼풀의 무통성 부종을 주소로 내원하였다. 조직 검사 결과 악성 점막연관 림프조직형 림프종으로 진단되었고 전신 전이나 골수 침범은 없어 항암화학요법을 시행하였다. 8차 항암요법 이후 양안 눈꺼풀은 외형적으로 정상, 영상학적으로 부분 관해 소견을 보여 경과관찰 중이다. 결론: 쇼그렌 증후군 등의 자가면역 질환이 있는 환자에서 눈꺼풀 부종이나 종괴가 촉지되는 경우에는 점막연관 림프조직형 림프종의 합병 가능성을 염두에 두어야 한다. <대한안과학회지 2016;57(7):1159-1164> Purpose: To report a case of lacrimal gland mucosa-associated lymphoid tissue (MALT) lymphoma in a patient with primary Sjögren’s syndrome and Behcet’s disease. Case summary: A 49-year-old female patient with primary Sjögren’s syndrome and Behcet's disease presented with a one-year history of painless upper and lower eyelid swelling in her right eye. Lacrimal gland incisional biopsy was performed, and the patient was diagnosed with malignant lymphoma (extranodal marginal zone B cell lymphoma of MALT). No distant metastases were detected on whole-body computed tomography or positron emission tomography, and the patient was treated with Rituximab, Cyclophosphamide, Vincristine, Prednisone (R-CVP) regimen chemotherapy. After 8 consecutive chemotherapy cycles, her eyelids appeared normal externally, and partial regression was found radiologically. Conclusions: The possibility of MALT lymphoma should be considered as a differential diagnosis if patients with autoimmune diseases such as primary Sjögren’s syndrome show eyelid swelling or palpable mass. J Korean Ophthalmol Soc 2016;57(7):1159-1164

Effect of anti-muscarinic autoantibodies on leukocyte function in Sjögren’s syndrome

Namkoong, Eun,Lee, Sang-woo,Kim, Nahyun,Choi, Youngnim,Park, Kyungpyo 3M Company 2017 Molecular immunology Vol.90 No.-

<P>Our results suggest that anti-M3R autoantibodies in primary Sjogren's syndrome induce downregulation of plasma membrane-resident M3R and MHC class I molecules in leukocytes followed by NK cell-mediated cell death. This mechanism may explain the frequency of leukopenia occurrence in patients with primary Sjogren's syndrome.</P>

쇼그렌증후군의 한방치료 1례

홍정수,안상민,추원정,최요섭,Hong, Jung-soo,Ahn, Sang-min,Choo, Won-jung,Choi, Yo-sup 대한한방내과학회 2016 大韓韓方內科學會誌 Vol.37 No.2

Objective: This case report examines the effects of Jaeumganghwa-tang as a treatment option for Sjögren’s syndrome.Methods: We provided the patient with Jaeumganghwa-tang twice a day, as well as acupuncture and bee venom therapy (both twice a week), for 30 days. Symptoms were charted and evaluated using the European League Against Rheumatism (EULAR) Sjögren’s Syndrome Patient Reported Index (ESSPRI).Results: The patient’s ESSPRI score decreased from 8 to 6 after the 30-day treatment.Conclusions: Jaeumganghwa-tang may be helpful in alleviating Sjögren’s syndrome.

The Interleukin 33/ST2 Axis in Patients with Primary Sjögren Syndrome: Expression in Serum and Salivary Glands, and the Clinical Association

Jung, Seung Min,Lee, Jaeseon,Baek, Seung Ye,Lee, Jae Ho,Lee, Jennifer,Park, Kyung-Su,Park, Sung-Hwan,Kim, Ho-Youn,Kwok, Seung-Ki Journal of Rheumatology Pub. Co 2015 The Journal of rheumatology Vol.42 No.2

<P>Objective. To evaluate the expression of interleukin 33 (IL-33) and its receptor in sera and salivary tissues of patients with primary Sjogren syndrome (pSS), and to investigate the association with clinical profiles. Methods. Serum IL-33 and soluble ST2 (sST2) of 55 patients with pSS and 48 controls were determined by ELISA and assessed for clinical correlation. The expression of IL-33/ST2 in salivary tissues was investigated by immunohistochemical staining and was further characterized by confocal microscopy. We also measured IL-33 production in salivary glandular epithelial cells by proinflammatory stimuli. Results. Serum levels of IL-33 and sST2 were higher in patients with pSS compared to those in controls (p = 0.018 and p < 0.0001, respectively). Among patients with pSS, sST2 concentration was associated with thrombocytopenia (p = 0.029) and correlated with disease duration (p = 0.013) and the European League Against Rheumatism Sjogren Syndrome Disease Activity Index (p = 0.042). The expression of IL-33 and ST2 was elevated in salivary glands of patients with pSS with grade 2 inflammation, and diminished in advanced inflammation. In patients with pSS, IL-33 was mainly observed in epithelial and endothelial cells of glandular tissue. The production of IL-33 mRNA by salivary gland epithelial cell line increased under stimulation with interferon-gamma. Conclusion. The expression of IL-33 and its receptor was elevated in sera and salivary tissues of patients with pSS. These results suggest that the IL-33/ST2 axis might have a role in the pathogenesis of pSS.</P>

Relation of Autoimmune Cytopenia to Glandular and Systemic Manifestations in Primary Sjögren Syndrome: Analysis of 113 Korean Patients

Koh, Jung Hee,Lee, Jennifer,Chung, So-Hyang,Kwok, Seung-Ki,Park, Sung-Hwan Journal of Rheumatology 2015 The Journal of rheumatology Vol.42 No.10

<P>Objective. To investigate the characteristics of patients with primary Sjogren syndrome (pSS) who have autoimmune cytopenia. Methods. We analyzed 113 participants from the Korean Initiative of Primary Sjogren Syndrome, a prospective pSS cohort. Autoimmune cytopenia was defined as autoimmune origin neutropenia, anemia, and/or thrombocytopenia without vitamin or iron deficiency, or drug-induced cytopenia. To identify the association between autoimmune cytopenia and the clinical characteristics of pSS, extraglandular manifestations were analyzed according to the European League Against Rheumatism Sjogren's syndrome disease activity index (ESSDAI) definition. Xerophthalmia was assessed with the Ocular Surface Disease Index, Schirmer I test, ocular stain score (OSS), and tear film breakup time. Results. The median total ESSDAI score was 2 (interquartile range 1-6). About a quarter of patients had no systemic activity. Autoimmune cytopenia was observed in 23.9% of patients (n = 27). Moderate biological features were more frequently observed in patients with autoimmune cytopenia than in patients without [10 (37%) and 11 (12.8%), respectively, p = 0.016]. Articular involvement was exhibited in 1 patient with autoimmune cytopenia, but in 23 patients (27.4%) without autoimmune cytopenia (p = 0.013). Higher OSS (p = 0.002) and lower mean Schirmer I test (p = 0.029) were observed in patients with autoimmune cytopenia than in those without. Neutrophils and lymphocytes negatively correlated with OSS (rho = -0.204, p = 0.041 and r = -0.230, p = 0.020, respectively). Conclusion. Autoimmune cytopenia is closely associated with severe ocular surface damage in pSS. Therefore, assessment of xerophthalmia by ophthalmologists may be mandatory, particularly in patients with pSS with cytopenia, even if patients do not complain of eye dryness.</P>