Immunoregulatory Role of Interleukin-37 in Rheumatoid Arthritis; Relation to Disease Activity and Joint Destruction

Background/Aim. Many arguments prove the pathophysiologic role of histamine in the process of remodeling and joint destruction in rheumatoid arthritis. The aim of our study was to find out if there was a relation between histamine concentration in synovial fluid and blood with clinical expression of disease activity. Methods. Histamine concentration in synovial fluid and blood was determinated in 19 patients with rheumatoid arthritis. Histamine concentration measurement was based on the Shore's fluorometric method. Histamine index (HI) was evaluated as a ratio between histamine concentration in synovial fluid and blood. Disease activity score, DAS 28 (3), with three variables (erythrocyte sedimentation rate, the number of swelled joints and the number of tender joints) was also evaluated. Results. Our results showed that there was no significant difference in concentration of histamine in synovial fluid and blood related to disease activity. However, there was a significant difference in the histamine index which was increased proportionally with disease activity. Conclusion. Our study indicates that histamine index could be useful in estimation of rheumatoid arthritis activity.

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Number of individual ACPA reactivities in synovial fluid immune complexes, but not serum anti-CCP2 levels, associate with inflammation and joint destruction in rheumatoid arthritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2017-212627 ◽

2018 ◽

Vol 77 (9) ◽

pp. 1345-1353 ◽

Cited By ~ 6

Author(s):

Azita Sohrabian ◽

Linda Mathsson-Alm ◽

Monika Hansson ◽

Ann Knight ◽

Jörgen Lysholm ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Fluid ◽

Disease Activity ◽

Immune Complexes ◽

Magnetic Beads ◽

Joint Destruction ◽

Joint Pathology ◽

A New Technique ◽

Laboratory Measures

IntroductionIndividual patients with rheumatoid arthritis (RA) show divergent specific anti-citrullinated protein/peptide antibodies (ACPA) patterns, but hitherto no individual ACPA specificity has consistently been linked to RA pathogenesis. ACPA are also implicated in immune complexes (IC)-associated joint pathology, but until now, there has been no method to investigate the role of individual ACPA in RA IC formation and IC-associated pathogenesis.MethodsWe have developed a new technique based on IC binding to C1q-coated magnetic beads to purify and solubilise circulating IC in sera and synovial fluids (SF) from 77 patients with RA. This was combined with measurement of 19 individual ACPA in serum, SF and in the IC fractions from serum and SF. We investigated whether occurrence of individual ACPA as well as number of ACPA in these compartments was related to clinical and laboratory measures of disease activity and inflammation.ResultsThe majority of individual ACPA reactivities were enriched in SF as compared with in serum, and levels of ACPA in IC were regulated independently of levels in serum and SF. No individual ACPA reactivity in any compartment showed a dominating association to clinical and laboratory measures of disease activity and severity. Instead, the number of individual ACPA reactivities in the IC fraction from SF associated with a number of markers of joint destruction and inflammation.ConclusionsOur data highlight the polyclonality of ACPA in joint IC and the possibility that a broad ACPA repertoire in synovial fluid IC might drive the local inflammatory and matrix-degrading processes in joints, in analogy with antibody-induced rodent arthritis models.

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Role of 14-3-3η (Eta) Protein as Immunological Marker for Disease Activity in Patients with Rheumatoid Arthritis

Indian Journal of Public Health Research & Development ◽

10.37506/v11/i2/2020/ijphrd/195165 ◽

2020 ◽

Vol 11 (2) ◽

pp. 2234

Author(s):

Muhannad Mohammed Ali AL-Salami ◽

Abeer Thaher Naji AL-Hasnawi ◽

Mohammed Abd AbdulHussein Abusabe

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Immunological Marker

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The Role of Synovial Fibroblasts in Mediating Joint Destruction in Rheumatoid Arthritis

Current Pharmaceutical Design ◽

10.2174/1381612053381945 ◽

2005 ◽

Vol 11 (5) ◽

pp. 563-568 ◽

Cited By ~ 40

Author(s):

Ingmar Meinecke ◽

Edita Rutkauskaite ◽

Steffen Gay ◽

Thomas Pap

Keyword(s):

Rheumatoid Arthritis ◽

Joint Destruction ◽

Synovial Fibroblasts

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POS0677 THE ROLE OF MUSCULOSKELETAL ULTRASOUND IN PREDICTING THE RESPONSE TO JAK INHIBITORS: RESULTS FROM A LARGE MONOCENTRIC COHORT

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3850 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 583-583

Author(s):

C. Garufi ◽

F. Ceccarelli ◽

F. R. Spinelli ◽

S. Mancuso ◽

C. Pirone ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Structural Damage ◽

Power Doppler ◽

Response To Treatment ◽

Jak Inhibitors ◽

Inflammatory Score ◽

Inflammatory Status

Background:In the management of chronic arthritis, such as Rheumatoid Arthritis (RA), Ultrasound (US) assessment can provide relevant information about the joint inflammatory status in the diagnostic phase and even more in the monitoring of disease activity and structural damage1,2.Objectives:In this longitudinal study, we aimed to assesse the role of US in predicting the efficacy of JAK-inhibitors (JAKi) in RA patients.Methods:We enrolled RA patients starting baricitinib or tofacitinib. All patients were evaluated at baseline and after 4, 12, 24, 48 weeks. Disease activity was calculated by DAS28CRP. US examination in 22 joints (I–V MCPs and PIPs, wrists) aimed at evaluating inflammatory features (synovial effusion and hypertrophy, power Doppler-PD), through a semi-quantitative scale (0-3). The total US (0-198) and PD (0-66) scores were calculated. We scanned bilateral flexor (I–V fingers of hands) and extensor compartments (1-6) tendons: tenosynovitis was scored as absent/present (0/1), resulting in a total score (0-22).Results:We studied 102 patients (M/F 15/87; median age 59.2 years, IQR 17.75; median disease duration 144 months, IQR 126), 61 treated with baricitinib and 41 with tofacitinib. At baseline, the median total US score was 18 (IQR 19) and the median PD score 2 (4). We observed a significant reduction in both total and PD US scores at all time-points (p<0.0001) (Figure 1). At baseline, 75.4% of patients showed tenosynovitis involving at least one tendon, with a median score of 2 (IQR 3.5) significantly decreasing after 24 weeks (p=0.02). Multivariate analysis, adjusted for baseline DAS28CRP and other concomitant treatments (including glucocorticoids and methotrexate treatment), confirmed the independent association between baseline US (PD and tenosynovitis) scores and the reduction of disease activity at follow-up evaluations.Conclusion:The present study confirmed the early efficacy of JAKi in RA patients by using US evaluation. Furthermore, power doppler and tenosynovitis scores could play a predictive role in response to treatment.References:[1]MUELLER RB, HASLER C, POPP F, et al. Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts. J Clin Med. 2019;8(10):1548.[2]COLEBATCH AN, EDWARDS CJ, ØSTERGAARD M, et al. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis. 2013;72(6):804-14.Figure 1.Ultrasound inflammatory score (a) and Ultrasound Power Doppler (PD) score (b) at baseline and follow-up.Table 1.Baseline characteristics of 414 RA patients.WEEKS04122448US inflammatory score18 (19)11 (15.5)9.5 (11.7)7.5 (8)6 (11)US PD score2 (4)0 (2)0 (1)0 (1)0 (0.7)Disclosure of Interests:Cristina Garufi: None declared, Fulvia Ceccarelli: None declared, Francesca Romana Spinelli Speakers bureau: Abbvie, Eli Lilly, Consultant of: Gilead/Galapagos, Eli Lilly, Grant/research support from: Pfizer, Silvia Mancuso: None declared, Carmelo Pirone: None declared, Fabrizio Conti Speakers bureau: Abbvie, Eli Lilly, Sanofi, Pfizer, Consultant of: Gilead/Galapagos

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FRI0127 Suppression of radiographic progression after gradual methotrexate tapering in patients with rheumatoid arthritis patients maintaining low disease activity - Prospective multicenter study-

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1415 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 645.1-645

Author(s):

K. Katayama ◽

K. Yujiro ◽

T. Okubo ◽

R. Fukai ◽

T. Sato ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Joint Destruction ◽

Reduction Rate ◽

Bone Destruction ◽

High Response ◽

Continuation Rate ◽

Low Disease Activity ◽

One Year ◽

Response Group

Background:Many studies have been reported to reduce/discontinue Biologics in the treatment of rheumatoid arthritis (RA). In contrast, study for tapering methotrexate (MTX) has been limited (1,2).Objectives:We prospectively examined whether bone destruction will progress at 48 weeks after tapering or discontinuing MTX (UMIN000028875).Methods:The subjects were RA patients who have maintained low disease activity or lower for 24 weeks or more in DAS28-CRP after MTX administration. Patients having PDUS Grade 2 or 3 per site by bilateral hand ultrasonography (26 area) were excluded in this study owing to risk for joint destruction. The joint destruction was evaluated by the joint X-ray evaluation by modified total Sharp scoring (mTSS) at 1 year after the start of tapering MTX. Evaluation of clinical disease activities, severe adverse events, the continuation rate during MTX tapering were also evaluated. According to tapering response, prognostic factor for good response for tapering, joint destruction was determined. Predictors for successful tapering MTX and progression of bone destruction were determined. Statistical analysis was performed by t-test or Wilcoxon rank sum test using SAS .13.2 software.Results:The subjects were 79 (16 males, 63 females). Age average 60.9 years, disease duration 4 years 4 months, MTX dose 8.43 mg / w, DAS28-CRP 1.52, DMARDs (24.3%), ACPA 192.7 U / ml (70.5%), RF 55.6 IU / ml (65.4%).MTX was tapered from an average of 8.43 mg / w before study to 5.46 mg / w one year later. In the treatment evaluation, DAS28-CRP increased from 1.52 to 1.84. 89.7% of subjects did not progress joint damage. Other disease activities significantly increased (Table 1). The one-year continuation rate was 78.2%. Since tapering effects were varied widely, we divided patients into three groups; Flared group (N=14, initial MTX dose 8.71mg/w, final MTX dose 8.42mg/w), Low response group (N=31, final MTX reduction rate< 50%, initial MTX dose 8.93mg/w, final MTX dose 6.22mg/w), High response group (N=34, final MTX reduction rate≥ 50%, initial MTX dose 8.5mg/w, final MTX dose 3.15mg/w)(Table 2).Higher RF value at baseline and higher MTX dose at 3M, 6M were predictors of whether a subject was in Low response group or High Response group. Higher RF value and mTSS at baseline and higher MTX dose at 6M were predictors whether a subject was in Flared group or High response group. Lower age was predictor of whether a subject was in Flared group or Low responder group. Finally, mean ΔmTSS /y in Flared group (0.36) was not significantly higher than in low response group (0.07) and in high response group (0.01).Table 1Table 2.Predictors for successful tapering MTX and progression of bone destructionConclusion:Patients with MTX-administered low disease activity and finger joint echo PDUS grade 1 satisfy almost no joint destruction even after MTX reduction. For tapering, predictors may be helpful for maintaining patient’s satisfaction.References:[1]Baker KF, Skelton AJ, Lendrem DW et al. Predicting drug-free remission in rheumatoid arthritis: A prospective interventional cohort study. J. Autoimmunity. 2019;105: 102298.[2]Lillegraven S, Sundlisater N, Aga A et al. Tapering of Conventional Synthetic Disease Modifying Anti-Rheumatic Drugs in Rheumatoid Arthritis Patients in Sustained Remission: Results from a Randomized Controlled Trial. American College of Rheumatology. 2019; Abstract L08.Disclosure of Interests:None declared

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Synovial Infiltration with CD79a-positive B Cells, But Not Other B Cell Lineage Markers, Correlates with Joint Destruction in Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.110615 ◽

2011 ◽

Vol 38 (11) ◽

pp. 2301-2308 ◽

Cited By ~ 16

Author(s):

YING-QIAN MO ◽

LIE DAI ◽

DONG-HUI ZHENG ◽

LANG-JING ZHU ◽

XIU-NING WEI ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

B Cells ◽

Disease Activity ◽

B Cell ◽

Cell Density ◽

Joint Destruction ◽

Chinese Patients ◽

Positive Staining ◽

Synovitis Score ◽

Sharp Score

Objective.The efficacy of B cell depletion in the treatment of patients with rheumatoid arthritis (RA) has revitalized interest in the pathogenic role(s) of B cells in RA. We evaluated the distribution of synovial B lineage cells and their correlation with histologic disease activity and joint destruction in RA.Methods.Synovial tissue samples were obtained by closed-needle biopsy from 69 Chinese patients with active RA, from 14 patients with osteoarthritis (OA), and from 15 with orthopedic arthropathies (OrthA) as disease controls. Serial tissue sections were stained immunohistochemically for CD79a (pro-B cell to plasma cell), CD20 (B cells), CD38 (plasma cells), CD21 (follicular dendritic cells), CD68 (macrophages), CD3 (T cells), and CD34 (endothelial cells). Densities of positive-staining cells were determined and correlated with histologic disease activity (Krenn 3-component synovitis score) and radiographic joint destruction (Sharp score).Results.Mean sublining CD79a-positive cell density was significantly higher in RA than in OA (p <0.001) or OrthA (p = 0.003). Receiver operating characteristic curve analysis showed that CD79a-positive cell density differentiated RA well from OA [area under the curve (AUC) = 0.79] or OrthA (AUC = 0.75). Spearman’s rank order correlation showed significant correlations between sublining CD79a-positive cell density and the synovitis score (r = 0.714, p < 0.001), total Sharp score (r = 0.490, p < 0.001), and the erosion subscore (r = 0.545, p < 0.001), as well as the joint space narrowing subscore (r = 0.468, p = 0.001) in RA.Conclusion.Synovial CD79a-positive B cells may be a helpful biomarker for histologic disease activity in RA and may be involved in the pathogenesis of joint destruction in RA.

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The Novel Role of MIF in the Secretion of IL-25, IL-31, and IL-33 from PBMC of Patients with Rheumatoid Arthritis

Molecules ◽

10.3390/molecules26164968 ◽

2021 ◽

Vol 26 (16) ◽

pp. 4968

Author(s):

Samuel García-Arellano ◽

Luis Alexis Hernández-Palma ◽

Sergio Cerpa-Cruz ◽

Gabriela Athziri Sánchez-Zuno ◽

Melva Guadalupe Herrera-Godina ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Mononuclear Cells ◽

Joint Destruction ◽

Study Groups ◽

Joint Disease ◽

The Novel ◽

Peripheral Blood Mononuclear ◽

Cytokine Dysregulation ◽

New Evidence

Rheumatoid arthritis (RA) is an autoimmune inflammatory joint disease with complex pathogenesis associated with cytokine dysregulation. Macrophage migration inhibitory factor (MIF) plays a role in systemic inflammation and joint destruction in RA and could be associated with the secretion of other immune-modulatory cytokines such as IL-25, IL-31, and IL-33. For the above, our main aim was to evaluate the IL-25, IL-31, and IL-33 secretion from recombinant human MIF (rhMIF)-stimulated peripheral blood mononuclear cells (PBMC) of RA patients. The rhMIF and lipopolysaccharide (LPS) plus rhMIF stimuli promote the secretion of IL-25, IL-31, and IL-33 (p < 0.05) from PBMC of RA patients. The study groups, the different stimuli, and the interaction between both showed a statistically significant effect on the secretion of IL-25 (p < 0.05) and IL-31 (p < 0.01). The study of the effect of the RA patient treatments and their interaction with the effect of stimuli did not show an interaction between them. In conclusion, our study generates new evidence for the role of MIF in the secretion of IL-25, IL-31, and IL-33 and its immunomodulatory effect on RA.

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