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Objective To investigate the secretory capacity and apoptosis of interleukin ( IL)-21 induced normal B cells by co-culture with serum from patients with systemic lupus erythematosus (SLE). Methods Serum from twenty new-onset SLE patients and 20 healthy donors were collected .CD1+9 B cells from the normal controls were co-cultured with serum from SLE patients in the presence or absence of IL-21-R-FC(4 μg/ml).Supernatant IgG and IgM concentration were measured by immunoturbidimetric assay on day 5.Supernatant anti-dsDNA level was determined by ELISA .The percentage of apoptotic cells was detected by flow cytometer.Results IgG,IgM and anti-dsDNA levels in normal B cells with SLE serum were significantly higher than those in the serum of SLE patients alone [ ( 5.84 ±1.79 ) g/L vs ( 4.25 ± 1.48)g/L,P=0.000;(0.46 ±0.21)g/L vs (0.43 ±0.21)g/L,P=0.003;(127.76 ±70.24)IU/ml vs (115.15 ±63.88) IU/ml,P=0.014 respectively].However, no significant differences were found in the group of normal B cells with non-homologous serum from normal controls (P>0.05).Supernatant IgG, IgM and anti-dsDNA levels in normal B cells with SLE serum significantly decreased while IL-21R-fusion protein was added [(5.26 ±1.62)g/L vs (5.84 ±1.79)g/L, P=0.006;(0.42 ±0.20)g/L vs (0.46 ±0.21)g/L, P=0.002;( 118.00 ±69.62 ) IU/ml vs ( 127.76 ±70.24 ) IU/ml, P =0.012 respectively ] .The apoptotic rate of B cells with SLE serum was significantly higher than that with normal serum [ ( 47.88 ± 12.65)%vs (38.86 ±10.32)%,P =0.004].But adding IL-21R-fusion conversed the apoptotic rates [(42.08 ±12.52)%vs (47.88 ±12.65)%,P=0.001].Conclusions SLE serum could induce normal B cells to form immunoglobulin secreting cells and producing autoantibodies , or apoptosis in pathological conditions.IL-21 might be considered as a potential therapeutic target of SLE .
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Objective To understand the clinical features of Behcet′s Disease( BD) with pulmonary hypertension( PH) .Methods The etiology, clinical features, treatment and prognosis of 25 patients with Bahcet′s disease ( BD) complicated with pulmonary hypertension ( PH) admitted in Peking Union Medical College Hospital from January 2000 to August 2015 were retrospectively reviewed.Results Total 912 BD patients were hospitalized during the same period, among whom 25 cases were complicated with PH accounting for 3%.There were 15 males (60%) and 10 females (40%), with the mean age of (33 ±12) years (range 19 to 66 years).The median interval from the diagnosis of BD to the onset of PH was 1 year (range 0 to 40 years).The most common cause of PH was heart valve disease (n=10, 40%), followed by pulmonary arterial stenosis or occlusion (n=6, 24%), pulmonary arterial aneurysm with thrombus (n=1, 4%), pulmonary thrombosis (n=1, 4%), cardiomyopathy (n=1, 4%);there were no causes identified in 6 cases (24%).Pulmonary arterial pressures estimated by echocardiography were 40 to 117 mmHg (1 mmHg=0.133 kPa) with a mean pressure of (60 ±22) mmHg.When the PH developed, elevated erythrocyte sedimentation rate ( ESR ) and increased hypersensitive C-reactive protein ( hs-CRP ) were founded in 48% ( 11/23 ) and 82% ( 14/17 ) of patients, respectively.After treated with glucocorticoid (96%,24/25), immunosuppressive agents(92%, 23/25), anticoagulation or thrombolysis(36%,9/25) and specific targeted vasodilator(32%,8/25), the levels of ESR and hs-CRP declined in 91% (10/11) and 71%(10/14) of patients, respectively; and pulmonary arterial systolic pressure declined in 50% of cases (8/16).Among 9 patients followed for 2 to 96 months, 4 died, 1 aggravated, 2 kept stable and 1 improved.Conclusion PH is an uncommon complication in disease.Heart valve disease, pulmonary artery involvement are the major causes of PH.The therapeutic effect and prognosis are poor.
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Objective To identify the clinical features of malignancy mimic vasculitis (MMV),and to increase the knowledge and alertness of MMV to avoid misdiagnosis and mistreatment.Methods Clinical records and laboratory index with test results were collected and retrospective study was employed to analyze twenty-four MMV patients,who were admitted to the department of Rheumatology of Peking Union Medical College Hospital during the period from January 2001 to January 2015.All data were analyzed by Fisher exact probability test.Results ① Twenty-four MMV took up to 2.5％ (24/927) of all the systemic vasculitis,and 0.15‰(24/157 883) of all the malignancy diagnosed during the same period.② The average age at the diagnoses being established was (43±19) years and the male to female was 3:1.③ Skin lesions (16/24),mucous injury (12/24),pulmonary involvement (10/24),thrombosis (7/24) and neurological involvement (7/24) were the mose common clinical manifestations that could mimic systemic vasculitis;Beh(c)et's disease (6/24),granulomatous with polyangiitis (6/24) and polyarteritis nodosa (5/24) were types of systemic vasculitis that MMV most frequently mimic.④ Among 22 MMV with definite pathological evidence,there were sixteen hematological malignancies and fourteen non-Hodgkin's lymphoma (NHL).⑤ For hematological malignancies mimic vasculitis patients,skin lesions (P=0.023),elevated LDH (P=0.046),leukocyte disorder (P=0.015) were more common than those nonhematological malignancy patients.⑥ Those with long disease duration (＞12 months) (n=6) tended to present more skin lesions (P=0.024) especially skin ulcers P=0.038) were than short course patients.Conclusion MMV should be proposed for those systemic vasculitis patients with atypical manifestations and poor response to routine therapy.Even if the disease duration is as long as more than 12 months,MMV should not be excluded imprudently as hematological malignancies could have long disease durations.
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Objective To explore the value of bone marrow megakaryocyte counts in predicting clinical response of thrombocytopenia (TP) in systemic lupus erythematosus (SLE) patients. Methods Thirty-one patients of SLE with severe TP (platelet ≤50×109/L) from Peking Union Medical College Hospital during 2007 to 2014 with appreciable bone marrow aspiration results were retrospectively analyzed. Their therapeutic responses were stratified and the correlation with clinical and laboratory findings including the megakaryocyte counts in bone marrow were evaluated with logistic multivariate regression. Results Totally fifteen patients obtained complete response (CR), eight patients obtained partial response (PR) and eight no response (NR). Megakaryocyte counts in bone marrow were (101±26)/slide, (156±48)/slide and (34±15)/slide respectively with statistically significant difference (χ2=6.632, P=0.036). Those NR patients had less megakaryocytes in their bone marrow compared with those with clinical response (CR+PR) (Z=-2.438, P=0.015). By ROC curve method, we found 20/slide might be a good cutoff of megakaryocyte counts in bone marrow for determining the therapeutic response of immunotherapy with a sensitivity of 91% and a specificity of 63% and a AUC (area under the curve) of 0.793. Those with 20/slide or less megakaryocytes in bone marrows only had a clinical effective response rate of 29% verse a response rate of 88% in those with more megakaryocytes in bone marrow. Conclusion Megakaryocyte counts in bone marrow may provide predictive value for therapeutic response of severe TP in SLE patients. Those patients with equal or less than 20/slide megakaryocytes in their bone marrow tend to have poor therapeutic response.
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Objective To re-evaluate the diagnoses of ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (nr-axSpA) and analyze the incidence and reason of misdiagnosis.Methods Patients who were previously diagnosed as AS and nr-axSpA before referrals to Peking Union Medical College Hospital (PUMCH) were re-evaluated by three rheumatologists of PUMCH according to the modified New York criteria for AS and Assessment of SpondyloArthritis international Society (ASAS) axial SpA classification criteria for nr-axSpA.Results Totally 87 prior AS patients and 53 prior nr-axSpA patients were enrolled in this study.After re-evaluation,57 patients were still diagnosed as AS and 16 patients were still diagnosed as nr-axSpA.The misdiagnosis incidences were 34.48％ and 69.81％,respectively.The misdiagnosis incidence of nr-axSpA was higher than that of AS (P ＜ 0.01).Conclusions The misdiagnosis of AS were mainly due to the misjudgment of sacroiliac joints by CT.The misdiagnosis of nr-axSpA were mainly due to the misjudgment of sacroiliac joints by magnetic resonance imaging.Moreover,the misuse of ASAS axial SpA classification criteria contributed to the misdiagnosis also.
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Objective To investigate the clinical features of neuromyelitis optica (NMO) and NMO spectrum disorders (NMOSD) with primary Sj(o)gren' s syndrome (pSS).Methods Eleven inpatients diagnosed as NMO secondary to pSS in Peking Union Medical College Hospital were retrospectively analyzed.Results Eleven patients of pSS with NMO were enrolled in this study,including 10 females and 1 male.The mean age was(35 ± 15)years old.The course of disease ranged from one month to 16 years,with a median of 10 months.The interval between optic nerve and spinal cord involvement was 3 months to 2 years.Eight patients had NMOSD as initial presentations of pSS.Eight patients had history of optic neuropathy.The most frequently involved spinal segment was cervical cord (10 cases) shown by magnetic resonance.Serum NMO-IgG antibodies were tested in 7 patients and 6 of them were positive.Conclusion NMOSD may present as an important and initial clinical manifestation of pSS,which suggesting the involvement of central nervous system.Autoimmune antibodies,NMO-IgG and imaging were supposed to be done for further evaluation of prognosis and therapy regimens.
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Objective To compare the phenotypes of abnormal CD4+CD25-Foxp3+ T cells with traditional regulatory T cells (CD4+CD25+Foxp3+) in patients with untreated new-onset lupus (UNoL) and investigate their clinical relevance. Methods The expressions of surface markers (CD25, CD127, CCR4, GITR, CTLA-4) and intracellular marker(Foxp3) on the peripheral blood mononuclear cells from twenty-two UNoL patients were analyzed by flow cytometry analysis, and their clinical relevance were assessed. Results There were no significant differences between CD4+CD25-Foxp3+ and CD4+CD25+Foxp3- T cells in the expressions of GITR, CTLA--4 and CCR4 (P>0.05), but they were significantly lower than those of CD4+CD25+ Foxp3+ T cells in UNoL patients (P<0.01). The percentages of CD127low- in CD4+Foxp3+CD25high,CD4+Foxp3+ CD25low and CD4+Foxp3+CD25+ T cells were (93.8±3.5 )%, (93.7±2.3)% and (92.0±2.1)% respectively (P> 0.05), whereas the expressions of Foxp3 on CD4+CD127low- T subpopulations showed significant differences in CD4+CDI27low-CD25high (91.4±2.6)%, CD4+CD127low-CD25low (71.9±3.3)% and CD4+CD127low-CD25- (9.0± 2.2)% T cells(P<0.01 ). The frequency of CD+CCR4+CD25high T cells correlated negatively with SLEDAI (r=-0.695,P<0.001).and it was significantly lower in lupus nephritis patients(1.10±0.17)%compared with SLE patients without nephritis [(1.61±0.23)%,P<0.01]and healthy controls [(1.75±0.10)%,P<0.01], furthermore,the frequency of CD4+CCR4+CD25low-T cells in lupus nephritis was significantly higher than that in healthy controls[(11.5±2.3)%vs (8.0±1.0)%,P<0.01].Conclusion The increased CD4+CD25-Foxp3+ T cells in the Untreated Newonset Lupus(UNoL)patients mimic activated T effector cells.CD4+CD25high-CD127low-T cells can be used to isolate live CD4+CD25highFoxp3+regulatory T cells.CCR4+regulatory T cells may be involved in the pathogenesis of lupus nephritis.
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Objective To investigate that p53 expression in fibroblast-like synoviocytes (FLS) and its effects on CD4+ T lymphocytes from active rheumatoid arthritis (RA) patients. Methods Human FLS was transfected with p53siRNA and cocultured with CD4+ T lymphocytes from active RA patients. The expression of osteoprotegerin and IL-6 secretion was detected in the transfected FLS. In addition, the expressions of IFN-γ, IL-17, IL-4 and CD25 as well as mRNA levels of IFN-γ RORγt, IL-17 and Foxp3 in cocuhured CD4+ T lymphocytes were also measured. Results IL-6 secretion decreased in p53-inhibited FLS while osteopro-tegerin expression was not altered, p53-inhibited FLS could significantly increase IL-17 and IFN-γ expres-sions. It also upregulated Foxp3 expression though had no effect on CD4+CD25high T lymphocytes. Conclusion p53 expression in FLS regulates Th1 and Th17 cells of RA patients, and therefore participate in the pathogenesis of RA.
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BAFF is an essential ligand essential for survival and differentiation of peripheral B cells. By interacting with three receptors, BAFF can promote B cell maturation and class switching, enhance humoral immunity and T cell co-stimulation. Over-expression of BAFF leads to autoimmune diseases such as systemic lupus erythematosus (SLE) in mouse model. Treating the mice model with BAFF antagonists can slow-down disease progression and enhance survival rate. Moreover, in some SLE patients serum level of BAFF is elevated and correlated with serum anti-dsDNA titer. The preliminary clinical trial of anti-BAFF monoclonal antibody has shown to be safe and effective. BAFF antagonists are promising therapeutic drugs for SLE.
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Objective To investigate the effects of Thalidomide(THD)on transdifferentiation of human fetal lung fibroblast(HFL-F) to myofibroblast(MF) induced by Transforming Growth Factor-?1(TGF-?1) and the effects on trans differentiated MF.Methods HFL-F to MF trans-differentiation was induced with 5 ?g/L TGF-?1.The effect of 50 ?g/L THD on HFL-F to MF transdifferentiation was evaluated by measuring hydroxyproline(HYP) content with alkaline hydrolysis colorimetry,?-smooth muscle actin(?-SMA) protein with Western Blot,?-SMA and collagen Ⅲ(COL Ⅲ) mRNA with semiquantitative RT-PCR.Results THD inhibited TGF-?1 induced up-regulation of HYP and COLⅢ mRNA expressions(all P0.05).For HFL-F treated with 5 ?g/L TGF-?1 for 96 h,THD inhibited COLⅢ mRNA expression(P