Expression Of Rheumatoid Arthritis Research Articles

Interferon-induced protein 44 (IFI44) and interferon regulatory factor 4 (IRF4) gene expression in rheumatoid arthritis

ABSTRACT Background and objectives The type I interferon (IFN) signature has been found to be overactivated in many systemic autoimmune diseases. This may be explained by impaired regulation of interferon-stimulated genes (ISGs) as well as interferon-induced protein 44 (IFI44) expression via their regulatory mechanisms via interferon regulatory factors (IRFs). Patients and methods This case-control study includes two groups: 50 RA patients and 50 healthy controls. The quantification of IFI44 and IRF4 expression levels by the real-time PCR technique was estimated. Disease Activity Score-28 (DAS-28) was estimated for RA patients only. Results Among the RA patients, there were statistically significant increased ESR, CRP, TLC, RF, and anti-CCP levels (p value < 0.001) and significant increased expression of the IFI44 and IRF4 genes (p value < 0.001). There was a significant positive correlation between the IFI44 and IRF4, and there was a significant correlation between both and ESR and anti-CCP among RA patients. At a cutoff point of 1.95, IFI44 shows higher sensitivity and specificity values than IRF4 for the diagnosis of RA. Conclusion IFI44 was more sensitive for RA diagnosis than IRF4. IFI44 and IRF4 overexpression could be promising predictors of RA diagnosis and might become useful clinical tools to guide therapeutic strategies.

Altered CD39 and CD73 Expression in Rheumatoid Arthritis: Implications for Disease Activity and Treatment Response.

In rheumatoid arthritis (RA) synovium, ATP, and ADP are released, sparking inflammation. Ectoenzymes CD39 and CD73 metabolize these purine nucleotides, generating anti-inflammatory adenosine. Therefore, dysregulated CD39 and CD73 expression may impact RA development. We assessed CD39 and CD73 expression in peripheral blood from 15 healthy controls (Cs) and 35 RA patients at baseline and after 3 and 6 months of tocilizumab treatment using flow cytometry. Additionally, ectoenzyme expression was examined on cultured T cells to understand activation and IL-6 effects. At baseline, RA patients exhibited a lower CD8+CD39-CD73+ cell percentage, which inversely correlated with DAS28. Additionally, they had lower percentages of Treg CD39+CD73+ and CD39-CD73- cells. Good responders tended to have lower B CD39+CD73+ cell percentages at baseline and 3 months. Additionally, Treg, CD8+ T and B cells inversely correlated with DAS28. T-cell activation increased CD39 and decreased CD73 expression, regardless of IL-6. IL-6 reduced IFNγ-secreting CD4+ T-cell percentage in Cs, but increased the percentage of IFNγ-secreting CD4+ and CD8+ T cells in RA patients. These findings indicate differing CD39 and CD73 expression in RA and Cs, influenced by T-cell activation and IL-6. Correlations between these molecules and RA activity suggest their role in dysregulated inflammation in RA.

The long non-coding RNA HOTAIR contributes to joint-specific gene expression in rheumatoid arthritis

Although patients with rheumatoid arthritis (RA) typically exhibit symmetrical joint involvement, some patients develop alternative disease patterns in response to treatment, suggesting that different molecular mechanism may underlie disease progression depending on joint location. Here, we identify joint-specific changes in RA synovium and synovial fibroblasts (SF) between knee and hand joints. We show that the long non-coding RNA HOTAIR, which is only expressed in knee SF, regulates more than 50% of this site-specific gene expression in SF. HOTAIR is downregulated after stimulation with pro-inflammatory cytokines and is expressed at lower levels in knee samples from patients with RA, compared with osteoarthritis. Knockdown of HOTAIR in knee SF increases PI-Akt signalling and IL-6 production, but reduces Wnt signalling. Silencing HOTAIR inhibits the migratory function of SF, decreases SF-mediated osteoclastogenesis, and increases the recruitment of B cells by SF. We propose that HOTAIR is an important epigenetic factor in joint-specific gene expression in RA.

Single-cell resolution of longitudinal blood transcriptome profiles in rheumatoid arthritis, systemic lupus erythematosus and healthy control pregnancies

ObjectivesComparative longitudinal analyses of cellular composition and peripheral blood gene expression in Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and healthy pregnancies.MethodsIn total, 335 whole blood samples from 84 RA,...

Role of miR-155 gene expression in Rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease that is prolonged, inflamed, and causes progressive disability, MicroRNAs appear to influence autoimmune disease processes through systemic consequences , including the immune system's irritant activities, in which specific antibodies with a high sensitivity for RA are the anti-CCP antibodies, Therefore, this research aims to evaluate the range of expression profile of circulating miRNA155 gene as a potential diagnostic biomarker in RA patients. The overall number comprised 36 RA patients, in addition to 14 healthy individuals as a comparison detection with ages ranging 20 to 60 years. All samples of patients and control suspected for diagnosed with anti-citrullinated protein antibodies test (ACPA) by immune assay for enzyme sorbent technique (ELISA). Relative quantification (RQ) of miRNA155 expression was performed after miRNA extraction from the serum of all study participants, was estimated using RT- qPCR. Significant Results noticed increased in expression of miRNA155 profile depending on the fold of expression (11.12 Fold expression ± 1.08), in comparison to a healthy people so as high significant (p ≤ 0.0001) of Anti-ccp Abs in patients with RA in which at risk and assessed the change in expression levels. In conclusion the study identified upregulation in circulated miRNA155 which may probably serve as prognostic form as biomarkers for disease in development.

Determination of miRNA -34a Expression in Rheumatoid Arthritis

Determination of miRNA -34a Expression in Rheumatoid Arthritis

SMRT and NCoR1 fine-tune inflammatory versus tolerogenic balance in dendritic cells by differentially regulating STAT3 signaling.

Dendritic cell (DC) fine-tunes inflammatory versus tolerogenic responses to protect from immune-pathology. However, the role of co-regulators in maintaining this balance is unexplored. NCoR1-mediated repression of DC immune-tolerance has been recently reported. Here we found that depletion of NCoR1 paralog SMRT (NCoR2) enhanced cDC1 activation and expression of IL-6, IL-12 and IL-23 while concomitantly decreasing IL-10 expression/secretion. Consequently, co-cultured CD4+ and CD8+ T-cells depicted enhanced Th1/Th17 frequency and cytotoxicity, respectively. Comparative genomic and transcriptomic analysis demonstrated differential regulation of IL-10 by SMRT and NCoR1. SMRT depletion represses mTOR-STAT3-IL10 signaling in cDC1 by down-regulating NR4A1. Besides, Nfkbia and Socs3 were down-regulated in Ncor2 (Smrt) depleted cDC1, supporting increased production of inflammatory cytokines. Moreover, studies in mice showed, adoptive transfer of SMRT depleted cDC1 in OVA-DTH induced footpad inflammation led to increased Th1/Th17 and reduced tumor burden after B16 melanoma injection by enhancing oncolytic CD8+ T-cell frequency, respectively. We also depicted decreased Ncor2 expression in Rheumatoid Arthritis, a Th1/Th17 disease.

Epigenetic regulator UHRF1 orchestrates proinflammatory gene expression in rheumatoid arthritis in a suppressive manner.

Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation with aberrant epigenetic alterations, eventually leading to joint destruction. However, the epigenetic regulatory mechanisms underlying RA pathogenesis remain largely unknown. Here, we showed that ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) is a central epigenetic regulator that orchestrates multiple pathogeneses in RA in a suppressive manner. UHRF1 expression was remarkably upregulated in synovial fibroblasts (SFs) from arthritis model mice and patients with RA. Mice with SF-specific Uhrf1 conditional knockout showed more severe arthritic phenotypes than littermate controls. Uhrf1-deficient SFs also exhibited enhanced apoptosis resistance and upregulated expression of several cytokines, including Ccl20. In patients with RA, DAS28, CRP, and Th17 accumulation and apoptosis resistance were negatively correlated with UHRF1 expression in synovium. Finally, Ryuvidine administration stabilized UHRF1 ameliorated arthritis pathogeneses in a mouse model of RA. This study demonstrated that UHRF1 expressed in RA SFs can contribute to negative feedback mechanisms that suppress multiple pathogenic events in arthritis, suggesting that targeting UHRF1 could be one of the therapeutic strategies for RA.

Analysis of TNFSF13B polymorphisms and BAFF expression in rheumatoid arthritis and primary Sjögren's syndrome patients.

BackgroundThe increased expression of B cell‐activating factor (BAFF) has been linked to autoantibody production in autoimmune diseases (ADs). The aim of this study was to investigate the association among TNFSF13B gene (OMIM: 603969) single nucleotide polymorphisms (SNPs), TNFSF13B mRNA, and soluble BAFF (sBAFF) expression in patients with rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS). The diagnostic value of sBAFF also was evaluated by the area under the curve (AUC) of receiver operating characteristic or receptor (ROC) curves.MethodsGenotypes of the TNFSF13B rs9514827 (−2841 T > C), rs1041569 (−2701 A > T) and rs9514828 (−871 C > T) SNPs were determined by PCR‐RFLP assay. TNFSF13B mRNA and sBAFF expression were performed by RT‐qPCR and ELISA, respectively. The study included 320 RA patients, 101 pSS patients, and 309 healthy subjects (HS).ResultsThe rs9514828 T allele and the TAT haplotype were associated with an increased risk to develop RA. In both ADs, the TNFSF13B mRNA levels were increased in comparison with HS. The rs9514828 (−871 C > T) polymorphism was associated with increased gene expression in RA patients. Also, sBAFF levels were higher in both ADs, however pSS patients showed the highest sBAFF levels. sBAFF showed higher diagnostic performance for pSS with an AUC of 0.968, with a similar accuracy of anti‐SSA/Ro antibody diagnosis (AUC = 0.974).ConclusionsOur findings demonstrate that the TNFSF13B rs9514828 (−871 C > T) polymorphism is a risk factor for RA in the western Mexican population. sBAFF levels may be a potential diagnosis biomarker in pSS.

Imaging of ανβ3 integrin expression in rheumatoid arthritis with [68Ga]Ga-NODAGA-RGDyk PET/CT in comparison to [18F]FDG PET/CT

[68Ga]Ga-NODAGA-RGDyk PET/CT and [18F]FDG PET/CT were performed in a 65-year-old woman during the work-up of a squamous cell carcinoma of the tongue within a clinical study protocol. Images revealed both tracers’ uptake in the primary tumor and cervical lymph nodes, but also bilaterally in the shoulders, elbows, wrists, metacarpophalangeal, interphalangeal, and hip joints. The patient had been diagnosed with rheumatoid arthritis 8 years prior to the examination. Images showed a significantly higher [18F]FDG than [68Ga]Ga-NODAGA-RGDyk uptake in primary tumor and cervical lymph nodes. However, the patient with moderately active rheumatoid arthritis had similar levels of [68Ga]Ga-NODAGA-RGDyk and [18F]FDG uptake in the involved joints, but with no [68Ga]Ga-NODAGA-RGDyk uptake in the surrounding muscles, unlike with [18F]FDG. Our case suggests that [68Ga]Ga-NODAGA-RGDyk PET/CT allows imaging of integrins expression in rheumatoid arthritis, including integrins expressed in synovial angiogenesis, with potentially a better signal-to-noise ratio than on [18F]FDG PET/CT.

Effect of IL-34 on T helper 17 cell proliferation and IL-17 secretion by peripheral blood mononuclear cells from rheumatoid arthritis patients

Interleukin (IL)-34 is a new pro-inflammatory cytokine with elevated expression in rheumatoid arthritis (RA) patients. Our previous study showed that the frequency of T helper 17 (Th17) cells was also elevated in RA patients. Our study aimed to determine the effects of IL-34 on the proliferation, transcription factor expression and cytokine secretion of different subgroups of CD4 + T cells [Th1, Th2, Th17 and regulatory T (Treg) cells] in RA patients. Peripheral blood mononuclear cells (PBMCs) were isolated from the peripheral blood of 10 RA patients and stimulated with different concentrations of recombinant human (rh) IL-34 (0, 25, 50 and 100 ng/ml). Flow cytometry was used to determine the frequencies of the 4 subgroups of CD4 + T cells. Reverse transcription-PCR, western blotting and enzyme-linked immunosorbent assays were used to determine the mRNA and protein expression levels of transcription factors and cytokines. As a result, the frequency of Th17 cells was obviously increased under IL-34 stimulation. Moreover, the expression of the transcription factor retinoic acid-related orphan receptor (ROR-γt) and secretion of IL-17 by PBMCs were increased by stimulation with IL-34. However, there were no effects of IL-34 on transcription factors or cytokine secretion in Th1, Th2 and Treg cells. In conclusion, IL-34 can improve the proliferation of Th17 cells and expression of IL-17 in RA patients.

Interleukin (IL)-25 suppresses IL-22-induced osteoclastogenesis in rheumatoid arthritis via STAT3 and p38 MAPK/I\u03baB\u03b1 pathway

BackgroundThe present study aimed to evaluate the suppressive role of interleukin (IL)-25 in IL-22-induced osteoclastogenesis and receptor activator of nuclear factor κB ligand (RANKL) expression in rheumatoid arthritis (RA).MethodsSerum from patients with RA and osteoarthritis (OA), and healthy controls, and synovial fluid from patients with RA and OA were collected, and the levels of IL-22 and IL-25 were measured. RA and OA synovial tissues were stained against IL-25. Fibroblast-like synoviocytes (FLSs) of patients with RA were cultured with IL-22, in the presence or absence of IL-25, and RANKL expression was measured by real-time PCR and enzyme-linked immunosorbent assay (ELISA). Human peripheral blood monocytes were cultured under IL-22/RANKL + M-CSF, with or without IL-25, and tartrate-resistant acid phosphatase (TRAP)-positive cells and osteoclast-related markers were investigated to determine osteoclastogenesis.ResultsSerum and synovial IL-25 levels in RA were upregulated compared to those in OA and healthy control, and elevated expression of IL-25 in RA synovial tissue was re-confirmed. IL-25 and IL-22 levels showed significant correlation in serum and synovial fluid. Pre-treatment of FLS with IL-25 reduced IL-22-induced RANKL expression at the RNA level. The suppressive effects of IL-25 were confirmed to occur through the STAT3 and p38 MAPK/IκBα pathways. IL-25 reduced osteoclast differentiation and suppressed the expression of osteoclast-related markers.ConclusionIn the current study, we demonstrated the regulatory effect of IL-25 on IL-22-induced osteoclastogenesis. Therapeutic approach involving augmentation of IL-25 regulatory response may serve as a novel treatment option for RA, especially by suppressing osteoclastogenesis.

Hsa_circ_0088036 promotes the proliferation and migration of fibroblast-like synoviocytes by sponging miR-140-3p and upregulating SIRT 1 expression in rheumatoid arthritis

Circular RNAs (circRNAs) have been demonstrated to play crucial roles in the development and progression of various types of cancers by serving as microRNA sponges to regulate the expression of target genes. Although in-depth studies of circRNAs have been conducted, their functional and pathological significance in autoimmune diseases, including rheumatoid arthritis (RA), remains unclear. Our previous study verified that hsa_circ_0088036 (circ0088036) is significantly elevated in peripheral blood mononuclear cells from patients with RA. The present study aimed to explore the roles of circ0088036 in the pathogenesis of RA. The circ0088036/miR-140−3p/silent information regulator 1 (SIRT 1) axis was predicted by bioinformatics tools. Circ0088036 was found to be aberrantly upregulated in fibroblast-like synoviocytes (FLSs) in RA compared with FLSs in osteoarthritis (OA). Functionally, upregulated circ0088036 promoted the proliferation and migration of RA-FLSs. Mechanistically, circ0088036 acted as a miR-140−3p sponge to upregulate SIRT 1 expression, subsequently promoting RA progression. In conclusion, this study revealed that circ0088036 may play an essential role in promoting synovial pathogenesis via the circ0088036/miR-140−3p/SIRT 1 axis in RA, providing new insight into circRNAs during RA progression.

The effect of methotrexate on neutrophil reactive oxygen species and CD177 expression in rheumatoid arthritis

Neutrophils are found in abundance in the synovial fluid of patients with rheumatoid arthritis (RA), where they are activated and show high reactive oxygen species (ROS) production. However, there is limited data on circulating neutrophils in peripheral blood of patients with RA in terms of ROS production, expression of activation markers and the effect of treatment with methotrexate (MTX) on ROS. This single-centre prospective study recruited patients of RA classified as per the 2010 ACR/EULAR criteria. In the cross-sectional arm, we included three groups, treatment-naïve RA (naïve-RA), MTX-treated RA (MTX-RA) and healthy controls, and compared ROS production and surface markers of neutrophil activation. In the longitudinal arm, we studied the change in neutrophil ROS production after 8 weeks of MTX treatment in naïve-RA patients. Neutrophil ROS production was measured by flow cytometry using dihydrorhodamine-123 (DHR) and by chemiluminescence using luminol. Surface expression of CD177, CD11b and CD64 was measured by flow cytometry. This study included 103 patients (50 naïve-RA, 53 MTX-RA) and 20 controls. Both naïve-RA and MTX-RA patients showed higher ROS production than healthy controls in unstimulated neutrophils in the DHR assay (p<0.001 and p=0.004). MTX-RA patients showed significantly lower ROS production than naive-RA, in both unstimulated (p=0.004) and PMA-stimulated neutrophils in the DHR assay (p=0.03). On longitudinal follow-up of 24 naïve-RA patients, there was a significant reduction of neutrophil ROS production (by 55% from baseline) (p<0.001) after 8 weeks of MTX. Neutrophil CD177 expression was higher in both naïve-RA and MTX-RA (trend) than controls (p=0.001 and p=0.09). MTX-RA neutrophils showed lower expression of CD177 than naïve-RA (p=0.01). CD11b expression was higher in MTX-RA compared to controls (p=0.01). Circulating neutrophils in RA showed higher ROS production and higher expression of CD177 and CD11b compared to controls. MTX treatment was associated with a reduction in ROS production and CD177 expression, which may be one of the mechanisms by which MTX works in RA.

CD40/TNF receptor associated factor 1 expression and NF-κB-dependent proinflammatory gene expression in rheumatoid arthritis

Objective: To investigatea cellular/molecular mechanism of the CD40/TRAF1 signalling pathway involved in Rheumatoid arthritis (RA). Methods: 16 patients with active RA and 9 patients with Fractures who underwent total knee or hip replacement in The First Affiliated Hospital of Soochow University were included in the study. Synovial tissues (ST) and serum were obtained from each patient. The CD40, TRAF1, NF-κB p65 were detected by ELISA and Immunohistochemistry in serum and tissue respectively. Real time-PCR (RT-PCR) was applied to measure NF-κB-related gene expression. Results: CD40 and TRAF1 positive area (%) in RA patients were 28.7±5.4, 34.3±4.8 respectively, which were significantly higher (P<0.05) than Fracture controls (21.2±9.5, 21.6±8.7 respectively). The expression of total NF-κB p65, and phospho-NF-κB p65 proteins, as well as NF-κB-related gene expression, including cytokines (TNFα, IL-6), chemokines (MCP-1),and adhesion molecules (ICAM-1) were significantly higher in the ST of RA patients compared to Fracture controls. Conclusion: It is thus possible that the CD40/TRAF1 pathway acted as a positive regulator through NF-κB activation and NF-κB-dependent proinflammatory genes in RA.

Analysis of gene expression in rheumatoid arthritis and related conditions offers insights into sex-bias, gene biotypes and co-expression patterns.

The era of next-generation sequencing has mounted the foundation of many gene expression studies. In rheumatoid arthritis research, this has led to the discovery of important candidate genes which offered novel insights into mechanisms and their possible roles in the cure of the disease. In the last years, data generation has outstripped data analysis and while many studies focused on specific aspects of the disease, a global picture of the disease is not yet accomplished. Here, we analyzed and compared a collection of gene expression information from healthy individuals and from patients suffering under different arthritis conditions from published studies containing the following clinical conditions: early and established rheumatoid arthritis, osteoarthritis and arthralgia. We show comprehensive overviews of this data collection and give new insights specifically on gene expression in the early stage, into sex-dependent gene expression, and we describe general differences in expression of different biotypes of genes. Many genes that are related to cytoskeleton changes (actin filament related genes) are differently expressed in early rheumatoid arthritis in comparison to healthy subjects; interestingly, eight of these genes reverse their expression ratio significantly between men and women compared early rheumatoid arthritis and healthy subjects. There are some slighter changes between men and woman between the conditions early and established rheumatoid arthritis. Another aspect are miRNAs and other gene biotypes which are not only promising candidates for diagnoses but also change their expression grossly in average at rheumatoid arthritis and arthralgia compared to the healthy condition. With a selection of intersecting genes, we were able to generate simple classification models to distinguish between healthy and rheumatoid arthritis as well as between early rheumatoid arthritis to other arthritides based on gene expression.

Evaluation of Toll-like Receptor 2 Gene Expression in Rheumatoid Arthritis and Correlation with the Disease Activity

Background: Rheumatoid Arthritis (RA) is an autoimmune, chronic, and systematic disease. It affects joints and bones. The exact etiology of RA is still unclear. Varied genetic and environmental factors have been associated with the increased risk for RA. Overactivation of Toll-Like Receptors (TLRs) could initiate the development of autoimmune diseases including RA. Objective: The aim of the study was to evaluate TLR2 gene expression in rheumatoid arthritis patients and investigate its correlation with the disease activity. Materials and Methods: This study included 60 patients and 20 healthy individuals. The patients were diagnosed with RA according to the 2010 American College of Rheumatology/ European League Against Rheumatism criteria (ACR/EULAR). All included subjects did not have any joint disorders and /or autoimmune diseases. RA disease activity was determined by the disease activity score of 28 joints. Whole blood was collected from all participants. Total RNA extraction was done. TLR2 mRNA expression was assessed by reverse transcription-PCR (RT-PCR). Results: TLR2 mRNA expression was found to be significantly higher in RA patients compared to healthy controls. Also, a strong positive correlation was found between TLR2 expression level and the disease activity score. A non significant positive correlation was found between TLR2 expression and serum Rheumatoid Factor (RF) level. Conclusion: TLR2 pathway may have an important role in RA pathogenesis and could be a new biomarker for diagnosis and monitoring disease activity.

Rheumatoid nodules in thyroid gland parenchyma as an expression of rheumatoid arthritis: a case report

BackgroundThe rheumatoid nodule is the most common extra-articular manifestation of rheumatoid arthritis. When present, it is readily identified in conventional hematoxylin and eosin sections.Case presentationWe report a case with several rheumatoid nodules in a thyroid gland of a 33-year-old Greek woman with a 3-year history of rheumatoid arthritis treated with methotrexate, after having total thyroidectomy for hypothyroidism.ConclusionTo the best of our knowledge, this is the first time that rheumatoid nodules have been encountered in the thyroid gland.

Upregulation of miR-221/222 expression in rheumatoid arthritis (RA) patients: correlation with disease activity.

miRNAs are noncoding RNA that play a critical role as fine regulators of gene expression at the posttranscriptional level within cells in numerous autoimmune diseases. miR-221/222 play a role in cancer by regulating cell proliferation, invasion and apoptosis. However, there have been insufficient studies on their role in rheumatoid arthritis (RA). This work is designed to analyze the miR-221/222 expression patterns in peripheral blood mononuclear cells (PBMCs) of patients with RA in comparison with healthy controls using quantitative RT-PCR, in a group of 30 RA patients and 20 healthy controls. The fold change of miR-221/222 expression in PBMCs was significantly elevated (p < 0.01) in RA patients compared with healthy controls. A positive correlation between expression levels of miR-221 and miR-222 was recorded (r = 0.303; p < 0.05). High miR-221/222 expression levels appeared to be elevated with high activity. miR-222 expression in high activity group of RA patients was significantly increased in relation to moderate (p < 0.01) and low (p < 0.001) activity ones with positive correlation (r = 0.363; p < 0.05) between the progress of disease activity and change in miR-222 expression level. ROC analysis showed a sensitivity of 70% and specificity of 75% for miR-221. In miR-222, the sensitivity of 80% and specificity of 70% were recorded. Our data shed some light on the role of miR-221/222 expression in RA patients, and their great potential value as new novel noninvasive biomarkers for disease detection. Therefore; further investigations are warranted to fully elucidate their role in rheumatoid.

Immunohistochemical Analysis of Inflammatory Rheumatoid Synovial Tissues Using Anti-Human Podoplanin Monoclonal Antibody Panel.

Podoplanin (PDPN) is a transmembrane sialoglycoprotein, which is expressed in several normal tissues and malignant tumors. Although PDPN expression in rheumatoid arthritis (RA) has been reported, the role of PDPN in RA and other arthritic conditions has not been fully elucidated. In this study, we examined PDPN expression in inflammatory synovial tissues using an anti-human PDPN (hPDPN) monoclonal antibody (mAb) panel to select the most useful one for evaluation of synovitis. Synovial tissue samples were obtained from 11 RA patients and 9 osteoarthritis (OA) patients undergoing joint surgery. PDPN-positive cells were immunostained by a panel of PDPN mAbs (NZ-1, LpMab-3, LpMab-7, LpMab-10, LpMab-12, LpMab-13, and LpMab-17), followed by cell grading of inflammation and cell counting of PDPN-positivity by a quantitative analyzer. Immunohistochemistry showed that PDPN was markedly expressed in both macrophage-like type A and fibroblast-like type B lining cells of the hyperplastic synovial lining cell layer, and macrophages and fibroblasts in the stroma of RA. Among anti-PDPN mAbs, LpMab-12 showed the highest score. In inflammatory OA synovium, PDPN expression was also detectable. Although LpMab-12 also showed the highest score in OA, the difference was not statistically significant. The inflammatory synovitis score of RA was significantly higher than that of OA. PDPN was expressed in inflammatory lining cells and sublining stroma of RA and OA synovium. In the seven anti-hPDPN antibodies examined, LpMab-12 was the most stainable antibody for PDPN in RA synovitis. Thus, LpMab-12 for PDPN has a possible and promising specific biomarker for evaluating synovitis in RA and inflammatory OA.