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.

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.

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.

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.

Objective : To investigate the relationship between the 24 h ambulatory blood pressure c ircadian rhythm abnormalities and kidney damage in the patients of lupus nephritis (LN) . Methods : A total of 103 patients with LN patients were enrolled retrospectively. All patients were accepted 24 h ambulatory blood pressure monitoring (ABPM) . The patients were divided into 2 groups according to the 24 h ambulatory blood pressure c ircadian rhythm, including nocturnal blood pressure meaning average declining during the day ( > 10% ) and non⁃dipper type blood pressure group ( < 10% ) . The kidney damage index of LN patients with or without hypertension or nocturnal blood pressure and non⁃dipper type blood pressure was analyzed. The influencing factors of the circadian rhythm of LN blood pressure were analyzed by binary Logistic regression. Results : Among the 103 LN patients, 66 patients were hypertension, 37 patients were none hypertension. Fifty⁃nine patients were non⁃dipper type blood pressure in LN with hypertension group, and 30 patients were non⁃dipper type blood pressure in LN without hypertension. There was no significant difference in the frequency of non⁃dipper type blood pressure between the two groups (81. 1% vs 89. 4% , χ2 = 1. 395, P = 0. 238) . Compared with hypertension group, the levels of serum creatinine (Z = 2. 911, P = 0. 004), urea ( Z = 3. 348, P = 0. 001) and uric acid levels ( t = 2. 017, P = 0. 047 ) were significantly higher than those of LN without hypertension patients, whereas the levels of glomerular filtration rate (eGFR) (Z = 4. 846, P < 0. 001) were significantly lower than those of LN without hypertension patients. In the group of LN with hypertension, the levels of uric acid (Z = 2. 893, P = 0. 004) were significantly higher than those of nocturnal blood pressure subgroup patients compared with no dipper type blood pressure subgroup patients, and the levels of eGFR (Z = 2. 017, P = 0. 0440) were significantly lower. Nevertheless, in the group of LN without hypertension, the kidney damage index had no significant difference between the two subgroups. Univariate and multivariate analysis showed that uric acid was associated with an abnormal rhythm of LN combined with hypertension. Conclusion Abnormal blood pressure rhythms are common in LN patients with or without hypertension. Renal damage significantly increases in the non⁃dipper group of LN compared with hypertension patients.

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.
Humans ; Osteoclasts/physiology* ; Arthritis, Rheumatoid/pathology* ; Inflammation/pathology* ; Bone and Bones/pathology* ; Bone Resorption/pathology*