ABSTRACT
Objective:To investigate the effect of myeloid-derived suppressor cells (MDSC) on pro liferation of B lymphocytes in rheumatoid arthritis (RA) patients.Methods:The peripheral blood specimens were collected from 15 healthy adults and 38 RA patients who were divided into high disease activity group,medium activity group and low activity group according to their 28-joint disease activity score (DAS28).And the frequencies of MDSC were determined by flow cytometry.Then,B cells and MDSC were isolated by flow cytometry,respectively.B cells were labeled with carboxyfluorescein diacetate suecinimidyl ester (CFSE) and then were co-cultured with MDSC in the presence of 3 mg/L anti-CD40 antibody and 10 mg/L CpG,for 3 days.Flow cytometry was performed to investigate the proliferation of B cells.Results:MDSC expanded markedly in high disease activity patients (7.13％ ±2.17％) compared with medium (5.35％ ±-1.36％) and low disease activity patients (4.72％ ± 1.08％) or healthy controls (4.79％ ± 1.02％) (P ＜ 0.05),and there were no statistical differences between healthy controls,medium and low disease activity RA (P ＞ 0.05).Moreover,the frequencies of MDSC were positively correlated with the DAS28 (P ＜ 0.05).After co-culture,MDSC significantly promoted B cell proliferation (P ＜0.01).Conclusion:Our studies showed that MDSC expanded obviously in high disease activity RA patients,and their frequencies were positively correlated with the disease activities.Furthermore,MDSC could promote autologous B cell proliferation remarkably in vitro.These findings suggest that MDSC might be involved in RA pathogenesis through regulating B cell functions.
ABSTRACT
Interstitial lung diseases (ILDs) are a diverse group of pulmonary disorders characterized by various patterns of inflammation and fibrosis in the interstitium of the lung.The underlying pathogene sis of ILDs is complex and associated with multiple rheumatologic conditions,such as systemic sclerosis,rheumatoid arthritis,pollymyositis and dermatomyositis,Sjt(o)gren's syndrome,and systemic lupus erythematosus.As the disease progresses,excessive pulmonary fibrosis impairs alveolar gas exchange and damages pulmonary function.The common methods to diagnose ILDs,such as clinical manifestations,pulmonary function test,and radiological examinations are not specific for ILDs and not able to diagnose ILDs at the early stage due to their low sensitivity.So,the easy way is important to diagnose ILDs.One important biomarker for ILDs is the high-molecular-weight glycoprotein,Krebs von den Lungen-6 (KL-6).KL-6 encoded by the MUC1 gene is a mucin-like glycoprotein with high molecular weight and expressed predominantly on the cell surface of type Ⅱ alveolar epithelial cells,and is detectable in the serum of patients with ILDs.We here report a case of ILDs associated with dermatomyositis and secondary Sj(o)gren's syndrome.A 60-year-old woman was admitted to our hospital with the chief complaints of debilitation,dry mouth,dyspnea and astasia.ILDs associated with dermatomyositis and secondary Sj(o)gren's syndrome was diagnosed clinically when the following criteria were satisfied:(1) development of dyspnea within 2 months of presentation,(2) pulmonary dispersion dysfunction,(3) bilateral infiltrative shadows on chest high resolution computed tomography (HRCT).She was treated with prednisone 50 mg/d prior to admission,but the result of therapy was not good.In our hospital she was treated with intravenous methylprednisolone and cyclophosphamide and oral hydroxychloroquine sulfate.Subsequently,her serum KL-6 levels gradually decreased after treatment,pulmonary diffuse function improved,and the improvement in the clinical manifestation and HRCT findings were observed.Nevertheless,the combination treatment of glucocorticoid and cyclophosphamide had contributed to the favourable outcomes.In conclusion,detection of serum KL-6 levels in ILDs associated with connective tissue diseases may be beneficial to making a definitive diagnosis,predicting the prognosis and monitoring the disease activity,which would be of great help in clinical practice.However,a well-designed clinical study with more patients and a longer follow-up period are required to arrive at a more conclusive judgment on the role of serum KL-6 in patients with ILDs.
ABSTRACT
Objective:To detect the levels of serum C-C chemokine ligand 19 (CCL19) in patients with systemic lupus erythematosus (SLE) and to evaluate the correlation between CCL19 expression and clinical features and laboratory parameters,trying to reveal the possible role of CCL19 in the pathogenesis of systemic lupus erythematosus.Methods:The levels of serum CCL19 were measured by enzyme linked immunosorbent assay (ELISA) in 90 patients with SLE and 30 healthy controls.These SLE patients included 75 patients who received treatment with glucocorticoids and disease-modifying anti-rheumatic drug (DMARD) and 15 patients without therapy.The frequencies of peripheral blood B cells and the B cell subsets were assessed in the patients with SLE by flow cytometry.The correlation between the clinical data,laboratory parameters,B cell subset frequencies and serum CCL19 levels were analyzed.Independent samples t test,paired t test,Pearson and Spearman correlation were used for statistical analyses.Results:The levels of CCL19 were markedly higher in the SLE patients without therapy and the patients with therapy than in the health controls[(596.25 ±409.19) ng/L and (422.90 ± 395.84) ng/L vs.157.79 ± 125.23) ng/L,all P ＜ 0.001].Serum CCL19 levels in the SLE patients without therapy were higher than the SLE patients who accepted glucocorticoids and DMARD treatment (P ＜ 0.05).The levels of serum CCL19 were positively correlated with anti-double stranded deoxyribonucleic acid (dsDNA),anti-nucleosome antibody (AnuA),IgA,IgG and IgM (r =0.38,P =0.007;r =0.332,P =0.029;r =0.519,P =0.007;r =0.461,P =0.018,respectively).Serum CCL19 levels in the SLE patients with photosensitivity,arthritis and secondary Sj(o)gren's syndrome were higher than the SLE patients without photosensitivity,arthritis and secondary Sj(o)gren's syndrome,respectively [(562.25 ± 399.12) ng/L,(565.6 ± 435.24) ng/L and (694.9 ± 531.02) ng/L vs.(394.7 ± 281.42) ng/L,(385.90-± 325.33) ng/L and (424.8 ± 305.46) ng/L,all P ＜ 0.05].The levels of serum CCL19 were positively correlated with the percentage of CD27-B cells and CD27-IgD-double-negative memory B cells (r =0.519,P =0.007;r =0.461,P =0.018,respectively).However,the levels of serum CCL19 were negatively correlated with the percentage of CD27 + memory B cells and CD27 + IgD-switched memory B cells (r =-0.433,P =0.027;r =-0.616,P =0.001,respectively).Conclusion:The increased serum CCL19 levels in SLE patients were associated with the production of autoantibodies,and CCL19 might be involved in the pathogenesis of SLE by disturbing the homeostasis of B cell subsets.