Significance of anti-Jo-1 antibody's clinical stratification in idiopathic inflammatory myopathy and disease spectrum / 北京大学学报(医学版)

OBJECTIVE@#To investigate the significance of anti-histidyl tRNA synthetase (Jo-1) antibody in idiopathic inflammatory myopathies (IIM) and its diseases spectrum.@*METHODS@#We enrolled all the patients who were tested positive for anti-Jo-1 antibody by immunoblotting in Peking University People's Hospital between 2016 and 2022. And the patients diagnosed with anti-synthetase antibody syndrome (ASS) with negative serum anti-Jo-1 antibody were enrolled as controls. We analyzed the basic information, clinical characteristics, and various inflammatory and immunological indicators of the patients at the onset of illness.@*RESULTS@#A total of 165 patients with positive anti-Jo-1 antibody were enrolled in this study. Among them, 80.5% were diagnosed with connective tissue disease. And 57.6% (95/165) were diagnosed with IIM, including ASS (84/165, 50.9%), immune-mediated necrotizing myopathy (7/165, 4.2%) and dermatomyositis (4/165, 2.4%). There were 23.0% (38/165) diagnosed with other connective tissue disease, mainly including rheumatoid arthritis (11/165, 6.7%), undifferentiated connective tissue disease (5/165, 3.0%), interstitial pneumonia with autoimmune features (5/165, 3.0%), undifferentiated arthritis (4/165, 2.4%), Sjögren's syndrome (3/165, 1.8%), systemic lupus erythematosus (3/165, 1.8%), systemic vasculitis (3/165, 1.8%), and so on. Other cases included 3 (1.8%) malignant tumor patients, 4 (2.4%) infectious cases and so on. The diagnoses were not clear in 9.1% (15 /165) of the cohort. In the analysis of ASS subgroups, the group with positive serum anti-Jo-1 antibody had a younger age of onset than those with negative serum anti-Jo-1 antibody (49.9 years vs. 55.0 years, P=0.026). Clinical manifestations of arthritis (60.7% vs. 33.3%, P=0.002) and myalgia (47.1% vs. 22.2%, P=0.004) were more common in the ASS patients with positive anti-Jo-1 antibody. With the increase of anti-Jo-1 antibody titer, the incidence of the manifestations of arthritis, mechanic hands, Gottron sign and Raynaud phenomenon increased, and the proportion of abnormal creatine kinase and α-hydroxybutyric dehydrogenase index increased in the ASS patients. The incidence of myalgia and myasthenia were significantly more common in this cohort when anti-Jo-1 antibody-positive ASS patients were positive for one and more myositis specific antibodies/myositis associated autoantibodies (P < 0.05).@*CONCLUSION@#The disease spectrum in patients with positive serum anti-Jo-1 antibody includes a variety of diseases, mainly ASS. And anti-Jo-1 antibody can also be found in many connective tissue diseases, malignant tumor, infection and so on.

Clinical and immunological characteristics of myositis complicated with thromboembolism / 北京大学学报(医学版)

OBJECTIVE@#To investigate and analyse the clinical and immunological features of patients with myositis complicated with thromboembolism.@*METHODS@#We identified a cohort of 390 myositis patients diagnosed with myositis admitted to People's Hospital of Peking University from 2003 to 2019. The patients were retrospectively enrolled in this investigation. According to the outcome of the color Doppler ultrasound, CT pulmonary angiography, pulmonary ventilation and perfusion scan patients were divided into myositis with and without thromboembolism group. Demographic, clinical (heliotrope rash, Gottron's sign/papules, periungual erythema, skin ulceration, subcutaneous calcinosis, Mechanic's hands, myalgia, interstitial lung disease, pulmonary arterial hypertension), laboratory, immunological [anti-autoantibodies including melanoma differentiation associated gene 5 (anti-MDA5), anti-Mi-2, anti-transcription intermediary factor-1γ (anti-TIF-1γ, anti-nuclear matrix protein 2 (anti-NXP2), anti-small ubiquitin-like modifier activating enzyme (anti-SAE), anti-synthetase], imaging and therapeutic status data of the patients at the diagnosis of myositis with and without thromboembolism were collected and the differences in these data were analyzed. Logistic regressive analysis was used to identify the risk factors of thromboembolism.@*RESULTS@#In the retrospective study, 390 myositis patients were investigated. The mean age of onset was (49.6±13.4) years, male to female ratio was 0.31 :1. Thromboembolism was identified in 4.62% (18/390) of the myositis patients, which was lower than the published reports. Out of 18 patients with thromboembolism, 55.6% (10/18) of them were deep venous thrombosis, followed by cerebral infarction (22.2%, 4/18), pulmonary embolism (11.1%, 2/18), renal artery embolism (5.6%, 1/18) and embolism of upper extremity (5.6%, 1/18). Fifty percent of thromboembolism events occurred 6 months after the diagnosis of myositis, 38.9% of thromboembolism events occurred 6 months within the diagnosis of myositis, 11.1% of thromboembolism events occurred 6 months before the diagnosis of myositis. As compared with the myositis patients without thromboembolism, the myositis patients complicated with thromboembolism were older [(58.3±11.7) years vs. (49.3±13.4) years, P=0.006]. C-reaction protein (CRP) (12.2 mg/L vs. 4.1 mg/L, P < 0.001), ferritin (20 085.5 μg/L vs. 216.6 μg/L, P < 0.001) and D-dimer (529.0 μg/L vs. 268.0 μg/L, P=0.002) were significantly higher in thromboembolism group. Diabetes (44.4% vs. 16.4%, P=0.006), coronary heart disease (22.2% vs. 3.0%, P=0.003) and surgery (16.7% vs. 3.5%, P=0.032) were observed more common in thromboembolism group than those without thromboembolism. Activated partial thromboplastin time (APTT) (26.9 s vs. 28.7 s, P=0.049) and albumin (32.4 g/L vs. 36.5 g/L, P=0.002) was lower in thromboembolism group. The risk factors of thromboembolism in the myositis patients were low level of albumin (OR=0.831, 95%CI: 0.736-0.939, P=0.003), diabetes (OR=4.468, 95%CI: 1.382-14.448, P=0.012), and coronary heart disease (OR=22.079, 95%CI: 3.589-135.837, P=0.001) were independent significant risk factors for thromboembolism in the patients with myositis. There was no significant difference in clinical manifestations, myositis-specific antibodies or myositis-associated antibodies between the two groups.@*CONCLUSION@#Thromboembolism is a complication of myositis. Lower levels of albumin, diabetes, and coronary heart disease might be risk factors of thromboembolism in myositis patients.

Association of Semaphorin 3A with thrombocytopenia in systemic lupus erythematosus / 北京大学学报(医学版)

OBJECTIVE@#To measure the level of serum Semaphorin 3A (Sema3A) and to analyze the relationship between serum Sema3A and systemic lupus erythematosus (SLE) with thrombocytopenia.@*METHODS@#The concentration of serum Sema3A was detected by enzyme-linked immuno sorbent assay (ELISA) in 170 SLE patients, 50 Sjögren's syndrome (SS) patients, 19 hypersplenism (HS) patients and 150 healthy controls (HC). Based on the presence of thrombocytopenia and whether the thrombocytopenia was in remission, the SLE patients were divided into three groups: SLE with thrombocytopenia (41 cases), SLE with thrombocytopenia remission (28 cases), and SLE without thrombocytopenia (101 cases). According to whether there was thrombocytopenia, the SS patients were divided into SS with thrombocytopenia (18 cases) and SS without thrombocytopenia (32 cases). The 28 SLE patients who underwent bone marrow aspiration biopsy were divided into two groups from the aspect of whether the bone marrow hyperplasia was normal (19 cases) or low (9 cases), as well as from the aspect of whether the maturity disturbance of megakaryocyte was positive (8 cases) or negative (20 cases). The serum Sema3A levels in SLE, SS, HS with HC were compared, meanwhile, the correlation between serum Sema3A level and platelet (PLT) in the patients with different diseases analyzed.@*RESULTS@#(1) Serum Sema3A levels in SLE were significantly lower than in HC [(3.84±2.76) μg/L vs. (6.96±2.62) μg/L, P < 0.001], serum Sema3A levels in SS were also obviously lower than in HC [(4.35±3.57) μg/L vs. (6.96±2.62) μg/L, P < 0.001], and in HS it was lower than HC at a certain extant [(5.67±2.26) μg/L vs. (6.96±2.62) μg/L, P=0.041]. (2) Serum Sema3A levels in SLE were slightly lower than in SS, but there was no significant difference [(3.84±2.76) μg/L vs. (4.35±3.57) μg/L, P=0.282]. However, when compared with HS, serum Sema3A levels in SLE were significantly lower [(3.84±2.76) μg/L vs. (5.67±2.26) μg/L, P=0.006]. (3) Serum Sema3A concentration in SLE with thrombocytopenia was significantly lower than in SLE with thrombocytopenia remission [(1.28±1.06) μg/L vs. (3.83±2.65) μg/L, P < 0.001], and in SLE patients without thrombocytopenia [(1.28±1.06) μg/L vs. (4.87±2.60) μg/L, P < 0.001]. There was no significant difference between SLE with thrombocytopenia remission and SLE without thrombocytopenia [(3.83±2.65) μg/L vs. (4.87±2.600 μg/L, P=0.123]. Serum Sema3A concentration in SLE with thrombocytopenia was slightly lower than in SS with thrombocytopenia, but there was no significant difference [(1.28±1.06) μg/L vs. (1.68±1.11) μg/L, P=0.189]. (4) Strong positive correlations were found between serum Sema3A and PLT in SLE (r=0.600, P < 0.001). Positive correlations were also found between serum Sema3A and PLT in SS (r=0.573, P < 0.001). However, there was no such correlation showed in HS patients (P=0.393). (5) There was no significant difference of serum Sema3A concentration in SLE whether the bone marrow hyperplasia was normal or low. And the same situation appeared in the patients whether the maturity disturbance of megakaryocyte was positive or negative (P>0.05).@*CONCLUSION@#Serum Sema3A was significantly reduced in SLE patients, and it was highly correlated with the blood damage. Similar conclusions could be drawn in patients with SS. The serum level of Sema3A was generally decreasing in desmosis which merged thrombocytopenia, and was obviously positive correlated with platelet counts.

Clinical Relevance of Autoantibodies against Interleukin-2 in Patients with Systemic Lupus Erythematosus / 中华医学杂志(英文版)

<p><b>Background</b>Increased serum autoantibodies against interleukin-2 (anti-IL-2 autoantibodies) were reported in patients with systemic lupus erythematosus (SLE) and in patients receiving IL-2 therapy. This study aimed to explore the clinical relevance of serum anti-IL-2 autoantibodies and the interactions between low-dose IL-2 therapy and serum anti-IL-2 autoantibodies.</p><p><b>Methods</b>Serum samples were collected from 152 SLE patients and 100 age- and gender-matched healthy controls (HCs). Among them, 75 SLE patients were followed up for 10 weeks, and all of them were treated with corticosteroids, antimalarials, and/or immunosuppressants. Forty-six out of the 75 SLE patients received low-dose IL-2 therapy additionally. Clinical and laboratory parameters were collected at baseline and week 10. Serum anti-IL-2 autoantibodies were determined by enzyme-linked immunosorbent assay.</p><p><b>Results</b>Compared with HCs, median levels and positive rates of serum anti-IL-2 autoantibodies were higher in SLE patients (32.58 [23.63, 45.23] arbitrary unit [AU] vs. 37.54 [27.88, 60.74] AU, P = 0.006, and 5.0% vs. 18.4%, P = 0.002, respectively). Compared to those without the corresponding disorders, serum anti-IL-2 autoantibody was increased in patients with alopecia (49.79 [36.06, 64.95] AU vs. 35.06 [25.40, 58.46] AU, P = 0.033), but it was decreased in those with lupus nephritis (31.71 [22.60, 43.25] AU vs. 44.15 [31.43, 68.52] AU, P = 0.001). Moreover, serum anti-IL-2 autoantibody was positively correlated with serum IgA (r = 0.229, P = 0.005), total IgG (r = 0.327, P < 0.001), and total IgM (r = 0.164, P = 0.050). Treatment with exogenous IL-2 was not significantly associated with serum anti-IL-2 autoantibody. In addition, no significant difference was found in serum anti-IL-2 autoantibody between responders and nonresponders to low-dose IL-2 therapy.</p><p><b>Conclusions</b>Serum anti-IL-2 autoantibody was increased and associated with disease severity in SLE. Exogenous low-dose IL-2 did not significantly induce anti-IL-2 autoantibody production.</p>

Dental pulp stem cells in tissue engineering: application and development / 中国组织工程研究

BACKGROUND: As a special source of stem cells, dental pulp stem cells (DPSCs) make much progress in the development of tissue engineering field due to their high proliferation and self-renewal ability. In the certain conditions DPSCs can be induced to differentiate into a variety of specialized tissue cells, providing a new way for tissue engineering development. OBJECTIVE: To review the main progress in the DPSCs biological characteristics, original source, isolation method, and its related application in tissue engineering research. METHODS: "Dental pulp stem cell, differentiation, regenerative medicine, tissue engineering" in English and Chinese were termed as the keywords to search relevant articles about DPSCs and tissue engineering published from 2005 to 2017 in PubMed, Medline, WanFang, and CNKI databases. After removal of repetitive or irrelevant articles, 66 articles were finally reviewed. RESULTS AND CONCLUSION: With the development of tissue engineering and regenerative medicine, the effective combination of DPSCs and tissue engineering scaffolds have be further achieved. Recent studies on DPSCs focus on the properties of DPSCs differentiating into odontoblasts and osteocytes/osteoblasts and on the potential of nerve repair, vascular remodeling, corneal reconstruction and chondrogenic differentiation.

Effect of light-cured adhesives on color relapse after cold light tooth whitening / 中国组织工程研究

BACKGROUND: Most studies suggest tooth whitening can create a coarse enamel surface which is likely to attract exogenous dyeing material and form the phenomenon of color relapse. After dental bleaching procedure, the use of resin surface treatment agent is expected to make the enamel surface smooth and alleviate tooth color relapse. OBJECTIVE: To unravel the efficacy of Adper Single Bond 2 Adhesive on color relapse phenomenon after dental bleaching treatment by cold light (xenon laser) whitening.METHODS: Twenty-four extracted teeth were collected and coated with 35% hydrogen peroxide followed by xenon laser whitening. The test group was made up of 12 samples coated with light-cured resin surface treatment agent and the left samples as control group were treated with no-coating agent after tooth whitening. Then the two groups were divided into two subgroups which were soaked in distilled water and tea for aging test respectively. The color differences (ΔE) which provided comparative values for statistical analysis was recorded at 1, 3, 5, 7, 14, 21, 28, 35 and 42 days after the aging test. The enamel surface microstructure of the samples was observed before and after bleaching, after resin agent coating, and 28 days after the aging test.RESULTS AND CONCLUSION: (1) Results from color differences observation: there was no significant difference between samples soaked in distilled water before and after whitening treatment (P > 0.05). Similarly, there was no statistical difference between test group and control group soaked in distilled water (P > 0.05). However, after soaking in tea, the color differences in the test group at 1-42 days showed statistically significant differences from those in the control group (P < 0.05). (2) Results from scanning electron microscope observation: after the tooth whitening producers, the enamel surface was damaged in the presence of cavities. After coated with resin surface treatment agent, the enamel surface became smooth and had few cavities. After soaking in tea, gradient smooth surface, some crack, inconspicuous flake dyeing color layer decomposition could be seen in the test group while rough surface with big holes and mottled dyeing layer were clearly visible in the control group. All samples soaked in distilled water had only a small amount of block dyeing layer, holes, weaker roughness than those soaked in tea. To conclude, Adper Single Bond 2 Adhesive light-cured resin surface treatment agent could weaken color relapse phenomenon after tooth whitening, achieving a smooth enamel surface and reducing dyeing material adhesion.

Effect of light-cured adhesives on color relapse after cold light tooth whitening / 中国组织工程研究

BACKGROUND: Most studies suggest tooth whitening can create a coarse enamel surface which is likely to attract exogenous dyeing material and form the phenomenon of color relapse. After dental bleaching procedure, the use of resin surface treatment agent is expected to make the enamel surface smooth and alleviate tooth color relapse. OBJECTIVE: To unravel the efficacy of Adper Single Bond 2 Adhesive on color relapse phenomenon after dental bleaching treatment by cold light (xenon laser) whitening.METHODS: Twenty-four extracted teeth were collected and coated with 35% hydrogen peroxide followed by xenon laser whitening. The test group was made up of 12 samples coated with light-cured resin surface treatment agent and the left samples as control group were treated with no-coating agent after tooth whitening. Then the two groups were divided into two subgroups which were soaked in distilled water and tea for aging test respectively. The color differences (ΔE) which provided comparative values for statistical analysis was recorded at 1, 3, 5, 7, 14, 21, 28, 35 and 42 days after the aging test. The enamel surface microstructure of the samples was observed before and after bleaching, after resin agent coating, and 28 days after the aging test.RESULTS AND CONCLUSION: (1) Results from color differences observation: there was no significant difference between samples soaked in distilled water before and after whitening treatment (P > 0.05). Similarly, there was no statistical difference between test group and control group soaked in distilled water (P > 0.05). However, after soaking in tea, the color differences in the test group at 1-42 days showed statistically significant differences from those in the control group (P < 0.05). (2) Results from scanning electron microscope observation: after the tooth whitening producers, the enamel surface was damaged in the presence of cavities. After coated with resin surface treatment agent, the enamel surface became smooth and had few cavities. After soaking in tea, gradient smooth surface, some crack, inconspicuous flake dyeing color layer decomposition could be seen in the test group while rough surface with big holes and mottled dyeing layer were clearly visible in the control group. All samples soaked in distilled water had only a small amount of block dyeing layer, holes, weaker roughness than those soaked in tea. To conclude, Adper Single Bond 2 Adhesive light-cured resin surface treatment agent could weaken color relapse phenomenon after tooth whitening, achieving a smooth enamel surface and reducing dyeing material adhesion.