S100A8 and S100A9 are major leukocyte proteins, known as damage-associated molecular patterns, found at high concentrations in the synovial fluid of patients with rheumatoid arthritis (RA). A heterodimeric complex of S100A8/A9 is secreted by activated leukocytes and binds to Toll-like receptor 4, which mediates downstream signaling and promotes inflammation and autoimmunity. Serum and synovial fluid levels of S100A8/A9 are markedly higher in patients with RA than in patients with osteoarthritis or miscellaneous inflammatory arthritis. Serum levels of S100A8/A9 are significantly correlated with clinical and laboratory markers of inflammation, such as C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and the Disease Activity Score for 28 joints. Significant correlations have also been found between S100A8/A9 and radiographic and clinical assessments of joint damage, such as hand radiographs and the Rheumatoid Arthritis Articular Damage score. In addition, among known inflammatory markers, S100A8/A9 has the strongest correlation with total sum scores of ultrasonography assessment. Furthermore, baseline levels of S100A8/A9 are independently associated with progression of joint destruction in longitudinal studies and are responsive to change during conventional and biologic treatments. These findings suggest S100A8/A9 to be a valuable diagnostic and prognostic biomarker for RA.
Arthritis, Rheumatoid/*blood/pathology/radiography ; Arthrography ; Biological Markers/blood ; Calgranulin A/*blood ; Calgranulin B/*blood ; Humans ; Joints/pathology ; Synovial Fluid/metabolism

OBJECTIVE: To investigate the expression of leukocyte immunoglobulin-like receptor A3 (LILRA3) in CD14 monocytes of patients with rheumatoid arthritis (RA). METHODS: Fifty three RA patients admitted in the Second Affiliated Hospital of Zhejiang University School of Medicine from February 2017 to August 2017, and 21 healthy subjects were enrolled in the study. The expression of LILRA3 in CD14 monocyte subset was determined by flow cytometry, and its correlations with clinical features, laboratory examination results, antibodies and disease activity were analyzed. RESULTS: LILRA3 percentage in the CD14 monocyte subset of RA patients was higher than that in the healthy controls (<0.01). The percentage of LILRA3 was positively correlated with number of tenderness joints, number of swollen joints and erythrocyte sedimentation rate (=0.280, 0.371, 0.341, <0.05 or <0.01), but was not correlated with the age, course of disease, Sharp score, C reactive protein, blood routine index and immunoglobulin (all >0.05). In addition, the percentages of LILRA3 in the monocytes of rheumatoid factor (RF)-positive or anti-cyclic citrullinated peptide (CCP) antibody-positive patients were significantly higher than those of the RF-or anti-CCP antibody-negative patients (all < 0.05); and the percentage of LILRA3 in patients with DAS28>5.1 was higher than that in patients with DAS28 ≤ 5.1 (<0.05). CONCLUSIONS The expression of LILRA3 is up-regulated in CD14 monocyte subset isolated from RA patients, and it is correlated with disease activity.
Arthritis, Rheumatoid ; blood ; physiopathology ; Autoantibodies ; blood ; Biomarkers ; blood ; Flow Cytometry ; Humans ; Monocytes ; metabolism ; Receptors, Immunologic ; genetics ; Up-Regulation

OBJECTIVETo detect the expressions of CCR5 and CCR7 on dendritic cells (DCs) in patients with rheumatoid arthritis (RA) in different phases of disease activity, and explore the relationship between the disease activity and the expression of chemokine receptors.

METHODSTwenty-eight patients with low, moderate and high disease activity and 10 normal control subjects were enrolled in this study. Peripheral blood was obtained from the subjects and the DCs were isolated. The expression of CCR5 and CCR7 on DCs were detected by flow cytometry, and the serum levels of rheumatoid factor (RF), C-reactive protein (CRP) and anti-CCP antibody (ACPA) were assessed. The correlation of the expressions of CCR5 and CCR7 to serum RF, CRP, and ACPA levels of the RA patients were analyzed.

RESULTSCompared to the normal control group, RA patients showed enhanced expressions of CCR5 and CCR7 on the DCs. A linear correlation was noted between CCR5 and CCR7 expressions on the DCs and the serum levels of RF and CRP, but not ACPA, in the RA patients.

CONCLUSIONThe expressions of CCR5 and CCR7 on the DCs may correlate to the disease activity of RA, and may serve as valuable indices in monitoring the disease activity and the efficacy of the treatment.

Adult ; Arthritis, Rheumatoid ; blood ; immunology ; Dendritic Cells ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Receptors, CCR5 ; metabolism ; Receptors, CCR7 ; metabolism

AIMTo determine the exact roles of prolactin (PRL) in the pathogenesis of rheumatoid arthritis (RA) and supply experimental basis for clinical treatment of RA, and to investigate the expression of matrix metalloproteinase-9 (MMP-9) in the synovium of adjuvant arthritis rats.

METHODSForty rats were divided into four groups (n = 10): (1) Normal control group (group A); (2) Adjuvant arthritis control group (group B); (3) Hyperprolactinemic adjuvant arthritis group (group C); (4) Hypoprolactinemic adjuvant arthritis group (group D). The content of PRL in the serum was detected by radio-immunoassay method. The activity of MMP-9 was analyzed by gelatin zymography. The alteration of MMP-9 immunoreactivity were investigated by means of immunohistochemistry in the synovium of all groups. The expressions of MMP-9 were investigated by Western blot in the synovium of all groups.

RESULTSCompared with group A, the activity and expression of MMP-9 of group B in the synovium were highly increased. The activity and expression of MMP-9 in the synovium were the most distinctive in group C. Compared with group B, the activity and expression of MMP-9 in the synovium were decreased in group D, but still higher than group A.

CONCLUSIONThe present results indicated that PRL might involved in the pathogenesis of RA by regulating the secretion of MMP-9 in the synovium.

Animals ; Arthritis, Experimental ; metabolism ; Arthritis, Rheumatoid ; physiopathology ; Male ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Prolactin ; blood ; physiology ; Random Allocation ; Rats ; Rats, Wistar ; Synovial Membrane ; metabolism

OBJECTIVETo investigate the expression levels of miR-146a and miR -16 in the peripheral blood mononuclear cells (PBMCs) of patients with rheumatoid arthritis (RA) and their correlation to the disease activity.

METHODSThe expression levels of miR-146a and miR-16 in the in PBMCs were measured using real-time RT-PCR in 40 RA patients and 16 healthy individuals. The correlations of miR-146a and miR-16 expressions to the disease activity of RA were analyzed.

RESULTSThe expression levels of miR-146a and miR-16 in the PBMCs of RA patients increased significantly compared to those in the healthy individuals (P<0.05). Their expression levels was significantly higher in active RA patients than in patients with disease remission (P<0.05) and healthy individuals (P<0.01). The expression levels of miR-146a and miR-16 were positively correlated to ESR, CRP and the disease activity scores in 28 joints (DAS28) (P<0.01), but not to RF (P>0.05).

CONCLUSIONThe elevated expression levels of miR-146a and miR-16 are correlated to RA disease activity, suggesting their value in assessment of the clinical disease activity of RA.

Adult ; Arthritis, Rheumatoid ; blood ; Biomarkers ; Female ; Humans ; Leukocytes, Mononuclear ; metabolism ; Male ; MicroRNAs ; genetics ; metabolism ; Middle Aged ; Young Adult

OBJECTIVETo explore the clinical efficacy of moxibustion on rheumatoid arthritis (RA) in the patients and the impacts on the inflammatory indices.

METHODSForty RA patients were randomized into an observation group and a control group, 20 cases in each one. In the control group, diclofenac sodium sustained release tablets were used, 0.3 g each time, twice a day; methotrexate tablets were used, 10 mg each time, once a week; folic acid was used, 5 mg each time, once a week. In the observation group, on the basis of the treatment as the control group, moxibustion was added specially on the swelling and painful joints, once a day, 15-20 min each time till: the local skin turned slightly red. The treatment was given once a day, at the interval of 1 day after every 6 treatments. In the two groups, the efficacy was observed after 30-day treatment. Before and after treatment, the rheumatoid factor (RF), high sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), disease activity score-28 (DAS-28) and the score of joint symptom and physical signs were observed.

RESULTSCompared with those before treatment, the levels of RF, hs-CRP, ESR, DAS-28 and the symptom scale score were all reduced in the RA patients of the two groups after treatment (all P < 0.05). Compared with the control group, the levels of RF, hs-CRP, ESR, DAS-28 and the symptom scale score in the observation group were improved much apparently (all P < 0.05). The total effective rate was 85.0% (17/20) in the observation group and was 80.0% (16/20) in the control group. The total effective rate in the observation group was apparently better than that in the control group (P < 0.05).

CONCLUSIONMoxibustion as supplement relieves the joint symptoms, reduces the inflammatory reactive indices and improves the clinical efficacy in the RA patients.

Adult ; Aged ; Arthritis, Rheumatoid ; blood ; therapy ; C-Reactive Protein ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Moxibustion ; Rheumatoid Factor ; blood ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the therapeutic effect of Liang's anti-rheumatism and rheumatoid granule (LARG) in treating patients with rheumatoid arthritis (RA) at the active stage.

METHODSFifty patients were administered orally with LARG in the treated group, 30 patients were treated with Wangbi granule in the control group. Symptoms, physical signs and relevant laboratory indexes in the 2 groups were observed and compared before treatment and after being treated for 2 months.

RESULTSThe total effective rate and curative-markedly effective rate in the treated groups were superior to those in the control group (P <0.01). The improvement in aspects of integral scoring of symptom and physical signs, including arthragia, tumefaction, dysfunction indexes, morning stiffness and 15m walking time, and laboratory indexes, including blood sedimentation rate, rheumatoid factor, C creative protein, immunoglobin, as well as hemorheology relevant indexes in the treated group after treatment were significantly different to those before treatment and those in the control group (P <0.05 or P <0.01).

CONCLUSIONLARG has obvious therapeutic effect on RA at the active stage.

Adult ; Arthritis, Rheumatoid ; drug therapy ; Blood Sedimentation ; C-Reactive Protein ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Phytotherapy ; Rheumatoid Factor ; blood

OBJECTIVES: To analyze arthritic manifestations in Behcet disease, which is one of the most common manifestations of Behcet disease. METHODS: Among the patients who visited the Rheumatology Division, Keimyung University Dongsan Medical Center, Taegu, Korea from March 1997 to February 1998, 35 patients, with more than 3 months follow-up, were compatible for the diagnosis of Behcet disease according to the Shimizu criteria, after exclusion of uncertain or possible Behcet cases. The presence of various manifestations was evaluated. Regarding the joint manifestations, the involved joint, signs and the pattern of the articular symptoms were examined. Basic laboratory tests, HLA studies and simple radiologic studies were done. RESULTS: All 35 patients had evident, recurrent, painful oral ulcers by the study definition. Genital ulcers were found in 29%, skin lesions in 77%, uveitis in 9%, gastrointestinal ulcerations in 6% and vascular manifestations in 6%. Joint manifestations appeared in 97%. Knee(91%), proximal interphalangeal (53%) and metacarpophalangeal joints(21%) were the main sites. Tenderness was prominent in 91% and swelling in 44%. Polyarticular presentation was found in 47%. In most cases (76.4%), the articular symptom was short-lasting. C-reactive protein was likely to be positive in active Behcet disease. HLA B51 was positive in 46%. CONCLUSIONS: In Behcet disease, various manifestations can be found. The arthritic manifestation seems quite common. It may present as seronegative rheumatoid arthritis. Otherwise, it may present as palindromic rheumatism.
Adult ; Arthritis, Rheumatoid/diagnosis* ; Arthritis, Rheumatoid/blood ; Behcet's Syndrome/diagnosis* ; Behcet's Syndrome/blood ; C-Reactive Protein/metabolism ; Comparative Study ; Diagnosis, Differential ; Female ; Human ; Joints/pathology ; Male ; Middle Age ; Rheumatic Diseases/diagnosis* ; Rheumatic Diseases/blood

Of the many theoretical causes of rheumatoid arthritis(RA), the most widely held theory is the autoimmune mechanism. In order to clarify the clinical significance of the immunological tests in RA, we studied immunoglobulin and complement levels in sera and synovial fluids of 118 RA patients and the following results were obtained. 1) The levels of immunoglobulins were elevated in both serum and synovial fluid and this was more prominent in the seropositive cases than the seronegative ones. 2) The levels of C3 component were decreased in both serum and synovial fluid, while those of C4 were decreased only in synovial fluid. Serum C3 and C4 component levels were more decreased in the seropositive cases than the seronegative ones. 3) The immunoglobulin levels in serum (IgG, IgM and IgA) and synovial fluid (IgG and IgA) and the levels of C3, C4 component in serum were well correlated with the clinical forms of rheumatoid arthritis. 4) The IgA level in serum and IgM level in synovial fluid were more increased in the exacerbated cases than the chronic ones. 5) Serum IgG level was decreased after steroid medication over one month.
Arthritis, Rheumatoid/blood/*immunology/metabolism ; Complement 3/analysis ; Complement 4/analysis ; Female ; Human ; Immunoglobulins/analysis ; Immunologic Tests ; Male

Gold Sodium Thiomalate (Myochrysine) used for rheumatoid arthritis has been known that it can cause the long term remission by its antimicrobial action, cell metabolism, complement activation and by activating the cell related to immunologic response. Accordingly the effect and side effect of gold theraphy has long been an object of concern. Authors clinically analyzed cases of 49 rheumatoid arthritis patients who were treated with gold and the mean duration of follow-up was 2.7 years. 50mg of Gold Sodium Thiomalate was injected intramuscularly in accordance with weekly based check up of symptom improvement & side effect. The interval of injection was prolonged and maintained to 4 weeks or 6 weeks when the total amount of injected gold was reached to 1gm or 1.2gm. The over-all symptom remission was forty (82%) and twenty five (51%) showed symptom remission and its maintenance. In symptom remission group, the change of laboratory findings was the reduction of erythrocyte sedimentation rate (ESR) from 59.7 to 32.3. As for side effects, dermatitis found in 16 cases was the most common and stomatitis found in 8 cases. There were others such as irritation symptom of gastrointestinal system & nephritis and 7 cases where the injection was stopped because of side effects was found out. Considering the above results, Gold Sodium Thiomalate is regarded as one of the effective methods for the treatment of rheumatoid arthritis when it is used electively paying heed to side effect.
Arthritis, Rheumatoid ; Blood Sedimentation ; Complement Activation ; Dermatitis ; Follow-Up Studies ; Gold Sodium Thiomalate ; Humans ; Metabolism ; Nephritis ; Stomatitis