Osteoimmunology research in rheumatoid arthritis: From single-cell omics approach / 中华医学杂志(英文版)

Cellular immune responses as well as generalized and periarticular bone loss are the key pathogenic features of rheumatoid arthritis (RA). Under the pathological conditions of RA, dysregulated inflammation and immune processes tightly interact with skeletal system, resulting in pathological bone damage via inhibition of bone formation or induction of bone resorption. Single-cell omics technologies are revolutionary tools in the field of modern biological research.They enable the display of the state and function of cells in various environments from a single-cell resolution, thus making it conducive to identify the dysregulated molecular mechanisms of bone destruction in RA as well as the discovery of potential therapeutic targets and biomarkers. Here, we summarize the latest findings of single-cell omics technologies in osteoimmunology research in RA. These results suggest that single-cell omics have made significant contributions to transcriptomics and dynamics of specific cells involved in bone remodeling, providing a new direction for our understanding of cellular heterogeneity in the study of osteoimmunology in RA.

The relationship between the frequency of dendritic cell subsets in peripheral blood and kidney damage in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective:To investigate the frequency of myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC) in peripheral blood of patients with systemic lupus erythematosus (SLE) and their relationship with renal injury.Methods:The frequency of peripheral mDC and pDC in 102 SLE patients and 10 healthy controls were detected by flow cytometry. The quantitative data were expressed by [ M( P25, P75)]. The measurement data of the two groups with non-normal distribution was analyzed by Mann Whitney U test. The correlation between the two groups was analyzed by Spearman rank correlation analysis and multiple linear regression. Results:The frequency of pDC [14.00%(7.92%, 19.65%) vs 24.55%(19.68%, 32.90%), Z=-3.163, P<0.01] and mDC [21.25%(13.28%, 32.83%) vs 34.85%(24.58%, 41.93%), Z=-2.607, P<0.01] in the peripheral blood of 102 patients with SLE were significantly lower than those of healthy controls. The frequency of pDC [9.09%(7.31%, 17.38%) vs 24.55%(19.68%, 32.90%), Z=-3.033, P=<0.01] and mDC [9.40%(7.88%, 21.60%) vs 34.85%(24.58%, 41.93%), Z=-3.231, P<0.01] in 12 patients with newly diagnosed SLE were also significantly lower than those in healthy controls. After adjustedfor confounding factors, multivariate analysis showed that SLEDAI level was the main factor influencing the frequency of pDC ( P=0.019) and mDC ( P<0.01). In addition, pDC[8.02%(2.25%, 9.97%) vs 16.70%(11.80%, 24.60%), Z=-2.490, P=0.015] and mDC[8.80%(5.99%, 12.80%) vs 20.20%(11.20%, 42.80%), Z=-2.226, P=0.029] in patients with active LN were also significantly lower than that of patients with stable LN. The mDC frequency was positively correlated with the levels of complement C3 ( r=0.455, P<0.01) and C4 ( r= 0.289, P, P<0.01). Conclusion:The frequency of mDC and pDC in SLE patients is significantly abnormal, which is closely related to disease activity. In addition, pDC and mDC may be involved in the occurrence and development of LN.

Peripheral regulatory T cells in systemic lupus erythematosus patients: the relationship with organ damage and the influence of treatment regimens / 中华风湿病学杂志

Objective To explore the distribution characteristics and function of peripheral regulatory T cells (CD4+CD25+Foxp3+T cells) in patients with systemic lupus erythematosus (SLE).In addition,we analyzed the relationship between peripheral regulatory T cells and organ damage and the influence of different treatment regimens on them.Methods Two hundred and six SLE patients and 38 healthy volunteers were enrolled,which included 12 patients with untreated new-onset lupus,11 patients with drug withdrawal more than six months and 183 patients with treatments.Phenotypic and functional analysis of peripheral blood CD4+CD25+Foxp3+T cells were performed by flow cytometry.The correlations of CD4+CD25+Foxp3+ T cells with disease activity,organ involvement were analyzed.Thealtered frequency of CD4+CD25 +Foxp3+T cells under different treatment regimens was compared.Statistical Package form Soci-science (SPSS) 21.0 software was used for data analysis,Student's t test,one-way ANOVA,Mann-Whitney T test,Kruskal-Wallis test,Chi-square test,Simple linear correlation analysis was used.Results CD4 +CD25 +Foxp3 + T cells were significantly increased inactive SLE patients [1 1.9％ (9.3％,16.0％),mean difference =104.71,P＜0.01] and inactive SLE patients [11.0％(7.7％,14.7％),mean difference=86.10,P＜0.01] compared with healthy controls [6.1％(5.3％,7.4％)].CD4+CD25+Foxp3+T cellsshowed sign-ificantly positive correlations with SLEDAI-2K (r=0.191,P＜0.05),dsDNA (r=0.262,P＜0.05),ESR (r=0.208,P＜0.05) and lgG (r=0.163,P＜0.05),and significantly negatively correlated with complementC3 (r=-0.201,P＜0.05) and C4 (r=-0.227,P＜0.05).Compared with patients without organ damage (Occult lupus),the CD4+CD25+Foxp3+T cells were increased in SLE patients with organ damage,especially those with skin involvement [10.9％(7.8％,13.1％),mean difference=56.93,P＜0.05] and renal involvement [12.1％(9.1％,16.0％),mean difference=77.26,P＜0.05].The proportion of CD4+CD25+Foxp3+T cells had no significant difference between SLE patients with treatments and patients with untreated new-onset lupus.The expressions of CTLA-4 [(53±15)％,t=7.04,P＜0.01],GITR [(42±19)％,t=2.64,P＜0.01] and ICOS [(28±9)％,t=4.27,P＜0.01] on CD4+CD25+Foxp3+T cells were significantly lower in SLE patients than in healthy controls [CTLA-4 (71±4)％,GITR (53±10)％ and ICOS (41±6)％].IL-17 synthesized by CD4+CD25+Foxp3+T cells in SLE patients [3.0％(1.8％,3.9％)] was significantly higher than that in healthy controls [1.0％(0.7％,1.2％),Z=-4.40,P＜0.01].Conclusion The peripheral regulatory T cells are significantly increased in SLE patients and correlate with disease activity and organ damage.However,their inhibitory function is defective and they have more pro-inflammatory character-istics.

Disturbance of peripheral blood B cells homeostasis in rheumatoid arthritis and the influence of therapy on B cells homeostasis / 中华风湿病学杂志

Objective To investigate the characteristics and the frequencies of B cell subsets in peripheral blood of rheumatoid arthritis (RA) patients,and to study the correlation between B cell subsets and clinical indices and influence of different therapies on B cell subsets to deeply understand the pathogenesis of RA.Methods Peripheral blood witched memory B cells,non-switched memory B cells,naive B cells,and double negative B cells of 141 patients and 33 healthy controls were measured by flow cytometry.Patients were divided into three groups based on their therapeutic regimen,including tumor necrosis factor-or (TNF-α) inhibitors combined with disease modifying antirheumatic drugs (DMARDs),DMARDs only and patients without any therapy.The relevance between B cells subsets and clinical manifestations,lab test results exemption were assessed as well as the influence of different therapies.All data were were analyzed by Statistical product and service solutions (SPSS) 23.0 statistical analysis for unpaired t test,analysis of variance and Spearman's correlations analysis.Results ① New-onset RA patients with less than 12 weeks disease duration and never accepted any drugs had a significantly lower frequency of peripheral blood memory B cells,including non-switched memory B cells [(8 ±4)％ vs (13 ±4)％,P＜0.05,t =3.3)] and switched memory B cells [(18±10)％ vs (23±7)％,P＜0.05,t=2.2)],than healthy individuals.② There was a negative association between non-switched memory B cells and disease activity score in 28 joints (r=-0.23,P＜0.05).③ Negative association between non-switched memory B cells and erythrocyte sedimentation rate (ESR),lgG was found,while therewas no association between pre-switched B cells and other laboratory test results.④ Non-switched memory B cells and switched memory B cells increased after TNF-α arntagonist or DMARDs therapy.Conclusion The results of this study suggest that B cell abnormalities in new-onset RA patients with short disease duration are reduced non-switched memory B cells and switched memory B cells.A negative correlation has been found between non-switched memory B cells and ESR and lgG.B cells subsets frequency are changed by TNF-α antagonist and DMARDs,which suggests that changes of B cell subsets may contribute to the occurrence and development of RA.

Clinical features and outcomes of seronegative rheumatoid arthritis in western China after one-year treatment with traditional disease modifying anti-rheumatoid drugs / 西安交通大学学报(医学版)

ABSTRACT:Objective To investigate the clinical features of seronegative rheumatoid arthritis (RA)in western China and its outcomes after one-year treatment with disease modifying anti-rheumatoid drugs (DMARDs) so as to provide evidence for effective therapy.Methods We made a retrospective analysis of 240 RA patients treated in our department from May 2013 to June 2014.We compared the 47 seropositive and 25 seronegative RA patients in clinical features,laboratory parameters and outcomes after one-year DMARDs medication.Results The percentage of seronegative RA was 10.4% (25/240).The number of swollen small joints was significantly smaller in seronegative RA group (P<0 .0 1 ).Compared with those in seropositive RA,the level of hemoglobin was lower,the level of platelets was higher,and the level of alkaline phosphatase was lower in seronegative RA (P<0 .0 5 ).The remission rate was higher in seronegative RA group than in seropositive RA group after one-year DMARDs administration (P<0.05).Conclusion Seronegative RA is not rare in clinic.Even though seronegative RA patients often present fewer swollen small joints, it is difficult to distinguish between seronegative and seropositve RA just based on the clinical features.Besides,hematological damage is more severe in some patients with seronegative RA.Only after one-year treatment with DMARDs,the remission rate is higher in seronegative RA patients than in seropositve RA ones.