New Treatments For Rheumatoid Arthritis Research Articles

Rheumatoid arthritis molecular targets and their importance to flavonoid-based therapy.

Rheumatoid arthritis (RA) is a progressive, chronic, autoimmune, inflammatory, and systemic condition that primarily affects the synovial joints and adjacent tissues, including bone, muscle, and tendons. The World Health Organization recognizes RA as one of the most prevalent chronic inflammatory diseases. In the last decade, there was an expansion on the available RA therapeutic options which aimed to improve patient's quality of life. Despite the extensive research and the emergence of new therapeutic approaches and drugs, there are still significant unwanted side effects associated to these drugs and still a vast number of patients that do not respond positively to the existing therapeutic strategies. Over the years, several references to the use of flavonoids in the quest for new treatments for RA have emerged. This review aimed to summarize the existing literature about the flavonoids' effects on the major pathogenic/molecular targets of RA and their potential use as lead compounds for the development of new effective molecules for RA treatment. It is demonstrated that flavonoids can modulate various players in synovial inflammation, regulate immune cell function, decrease synoviocytes proliferation and balance the apoptotic process, decrease angiogenesis, and stop/prevent bone and cartilage degradation, which are all dominant features of RA. Although further investigation is necessary to determine the effectiveness of flavonoids in humans, the available data from in vitro and in vivo models suggest their potential as new disease-modifying anti-rheumatic drugs. This review highlights the use of flavonoids as a promising avenue for future research in the treatment of RA.

TAGAP activates Th17 cell differentiation by promoting RhoA and NLRP3 to accelerate rheumatoid arthritis development.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that can give rise to joint swelling and inflammation, potentially affecting the entire body, closely linked to the state of T cells. The T-cell activation Rho GTPase activating protein (TAGAP) is associated with many autoimmune diseases including RA and is directly linked to the differentiation of Th17 cells. The present study intends to investigate the influence of TAGAP on the RA progression and its mechanism to empower new treatments for RA. A collagen-induced-arthritis (CIA) rat model was constructed, as well as the extraction of CD4+ T cells. RT-qPCR, H&E staining and safranin O/fast green staining revealed that TAGAP interference reduced TAGAP production in the ankle joint of CIA rats, and joint inflammation and swelling were alleviated, which reveals that TAGAP interference reduces synovial inflammation and cartilage erosion in the rat ankle joint. Expression of inflammatory factors (TNF-α, IL-1β, and IL-17) revealed that TAGAP interference suppressed the inflammatory response. Expression of pro-inflammatory cytokines, matrix-degrading enzymes, and anti-inflammatory cytokines at the mRNA level was detected by RT-qPCR and revealed that TAGAP interference contributed to the remission of RA. Mechanistically, TAGAP interference caused a significant decrease in the levels of RhoA and NLRP3. Assessment of Th17/Treg levels by flow cytometry revealed that TAGAP promotes Th17 cells differentiation and inhibits Treg cells differentiation in vitro and in vivo. In conclusion, TAGAP interference may decrease the differentiation of Th17 cells by suppressing the expression of RhoA and NLRP3 to slow down the RA progression.

Trends of adverse events and mortality after DMARDs in patients with rheumatoid arthritis: Interrupted time-series analysis.

ObjectivesPatients with rheumatoid arthritis (RA) experience adverse events because of the characteristics of the disease and the side effects of medications. We investigated the trends of adverse events and mortality associated with disease‐modifying antirheumatic drugs (DMARDs).MethodsWe used the Taiwan National Health Insurance Database to enroll patients with incident RA between 2000 and 2017. The 1‐year incident rate of gastrointestinal (GI) bleeding and 3‐year incident rates of other adverse events and mortality for each calendar‐quarter cohort were computed and adjusted using propensity score‐based stabilized weights for fair comparisons. Levels and trends of the conventional DMARD era (2000–2002, Phase 1) were compared with those of the TNFi era (2003–2012, Phase 2) and OMA era (2013–2017, Phase 3) by using interrupted time series (ITS) analysis.ResultsAll patients with RA were prescribed cDMARDs in Phase 1 (2000–2002), and 1%–3% were prescribed either TNFi in phase 2 (2003–2012) or OMAs in phase 3 (2013–2017). The cancer incidence rate was 1.90%, and its mortality rate was 4.19%. After the introduction of TNFi from 2003 to 2012, the main outcomes, except TKA, exhibited a steady or mild decrease in trends. ITS analysis revealed that the slope mildly increased in 2003–2012 compared with that in 2000–2003 by 0.13% for total knee replacement (p = .0322). In 2012–2017 (the OMA era), the events became steady.ConclusionIn patients with RA, the introduction of DMARDs was associated with stable adverse events and mortality rates. Moreover, the introduced new treatment for RA exhibited a good safety profile.

Benefit-Risk Analysis of Upadacitinib Compared with Adalimumab in the Treatment of Patients with Moderate-to-Severe Rheumatoid Arthritis.

IntroductionRheumatoid arthritis (RA) is a chronic autoimmune disease requiring long-term treatment. Upadacitinib (UPA), a Janus kinase (JAK) inhibitor, is a new treatment for RA. The benefit–risk profile of a medication is best understood by evaluating the number needed to treat (NNT) and the number needed to harm (NNH). This analysis evaluated the comparative risk–benefit of UPA versus adalimumab (ADA).MethodsPost-hoc analyses were performed using data from the SELECT-COMPARE trial of UPA versus placebo (PBO) and UPA versus ADA among patients with active RA who remained on stable methotrexate (MTX) treatment and had an inadequate response; patients who failed to achieve response were rescued by predefined criteria—PBO or ADA switch to UPA, and UPA switch to ADA (all patients on PBO were switched to UPA at week 26). This analysis assessed efficacy and adverse events of special interest (AESIs) at week 26, 48, and 156 (3 years). NNT and NNH (95% confidence intervals) values were calculated between UPA versus ADA for all time points, and between UPA versus PBO for week 26. NNT and NNH values were applied to a hypothetical cohort of 100 patients to estimate the comparative efficacy and safety profiles.ResultsUPA consistently showed greater efficacy than ADA, as evidenced by NNT values < 10 for achievement of Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP) of < 2.6 and ≤ 3.2, respectively, and functional improvement. Based on indices for disease assessment other than the DAS28-CRP, remission outcomes were higher with UPA versus ADA over 26 weeks (NNTs: 7–12), 48 weeks (NNTs: 9–16), and 156 weeks (NNTs: 9–15). With the exception of herpes zoster, other AESIs demonstrated a similar risk with UPA versus ADA.ConclusionIn patients with active RA despite MTX use, UPA demonstrated an incremental achievement of clinical outcomes compared to ADA together with a similar profile of AESIs with ADA (with the exception of herpes zoster).Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00399-5.

Therapeutic potential of russelioside B as anti-arthritic agent in Freund's adjuvant-induced arthritis in rats

Ethnopharmacological relevanceCaralluma species are traditional edible herbs used in folkloric medicine as antidiabetic, antioxidant, antipyretic, antirheumatic, anti-inflammatory and anthelmintic agents. C. quadrangula was selected in this study to document the traditional use of the genus as anti-rheumatic treatment and the possible mechanisms of action. Aim of the studyThe higher mortality rates and shorter survival among the patients suffering from rheumatoid arthritis (RA) led to the increased interest on searching for new treatments for RA. Russelioside B (RB), a major pregnane glycoside found in C. quadrangula, was evaluated as a new anti-rheumatic agent. Materials and methodsThe n-butanol fraction of C. quadrangula was chromatographed on a silica gel column to isolate RB. The adjuvant-induced arthritis (AIA) model was established in rats by intradermal injection of complete Freund's adjuvant (CFA) to evaluate its anti-arthritic effect. Ibuprofen was used as a reference drug. Forty rats were randomly divided into 5 groups (n = 8): normal (NOR); CFA model (CFA); ibuprofen, 5 mg/kg; RB, 25 mg/kg and RB, 50 mg/kg. The treatments were initiated from day 16 when AIA model was established and continued up to day 40. Serum diagnostic rheumatoid markers, inflammatory cytokines, oxidative stress biomarkers, cartilage and bone degeneration enzymes were assessed. ResultsRB at 50 mg/kg b. wt., showed significant decreases in the activities of hyaluronidase and β-glucouronidase enzymes as well significant decreases in the levels of proinflammatory cytokines as nuclear factor-kappa-B (NF-κB), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) compared to the CFA group; 11.04 ± 0.61 pg/mg protein, 4.35 ± 0.25 pg/mg protein, 3.32 ± 0.13 pg/mg protein & 2.75 ± 0.14 pg/mg protein for RB, 50 mg/kg b. wt. group vs. 25.33 ± 2.13 pg/mg protein, 25.65 ± 2.1 pg/mg protein, 22.20 ± 1.34 pg/mg protein & 13.27 ± 1.40 pg/mg protein for the arthritic group, respectively. The total antioxidant capacity (TAC) was significantly restored to normal values in RB, 50 mg/kg treated rats (4.01 ± 0.09 nmol/mL vs. 3.71 ± 0.27 nmol/mL) and the levels of myeloperoxidase (MPO) reduced by 10-folds of the CFA arthritic group. Bone histomorphometry revealed that RB treatment significantly attenuated the CFA-induced bone loss in a dose-dependent manner. ConclusionsThese findings suggested that the anti-arthritic effect of RB was mediated through the reduction of the rheumatoid markers, anti-inflammatory and antioxidant action, inhibition of cartilage and bone degenerative enzymes as well as attenuation of bone loss and osteoclastogenesis.

Huntingtin-interacting protein 1 (HIP1) regulates arthritis severity and synovial fibroblast invasiveness by altering PDGFR and Rac1 signalling

ObjectivesWhile new treatments for rheumatoid arthritis (RA) have markedly improved disease control by targeting immune/inflammatory pathways, current treatments rarely induce remission, underscoring the need for therapies that target other aspects...

Kaempferol targeting on the fibroblast growth factor receptor 3-ribosomal S6 kinase 2 signaling axis prevents the development of rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the synovial joints. Although involvement of the fibroblast growth factor (FGF) signaling pathway has been suggested as an important modulator in RA development, no clear evidence has been provided. In this study, we found that synovial fluid basic FGF (bFGF) concentration was significantly higher in RA than in osteoarthritis (OA) patients. bFGF stimulates proliferation and migration of human fibroblast-like synoviocytes (FLSs) by activation of the bFGF-FGF receptor 3 (FGFR3)-ribosomal S6 kinase 2 (RSK2) signaling axis. Moreover, a molecular docking study revealed that kaempferol inhibited FGFR3 activity by binding to the active pocket of the FGFR3 kinase domain. Kaempferol forms hydrogen bonds with the FGFR3 backbone oxygen of Glu555 and Ala558 and the side chain of Lys508. Notably, the inhibition of bFGF-FGFR3–RSK2 signaling by kaempferol suppresses the proliferation and migration of RA FLSs and the release of activated T-cell-mediated inflammatory cytokines, such as IL-17, IL-21, and TNF-α. We further found that activated phospho-FGFR3 and -RSK2 were more highly observed in RA than in OA synovium. The hyperplastic lining and sublining lymphoid aggregate layers of RA synovium showed p-RSK2-expressing CD68+ macrophages with high frequency, while pRSK2-expressing CD4+ T-cells was observed at a lower frequency. Notably, kaempferol administration in collagen-induced arthritis mice relieved the frequency and severity of arthritis. Kaempferol reduced osteoclast differentiation in vitro and in vivo relative to the controls and was associated with the inhibition of osteoclast markers, such as tartrate-resistant acid phosphatase, integrin β3, and MMP9. Conclusively, our data suggest that bFGF-induced FGFR3–RSK2 signaling may play a critical role during the initiation and progression of RA in terms of FLS proliferation and enhanced osteoclastogenesis, and that kaempferol may be effective as a new treatment for RA.

Rheumatoid Arthritis Portrayal by UK National Newspapers 2011\u20132016: A Service User - Led Thematic Analysis of Language Used

BackgroundAn important source of knowledge, beliefs, and attitudes about illness is the mass media. Research has established the often negative and emotive language utilised by journalists to report on physical and mental long-term illnesses. The limited amount of research on rheumatological conditions has largely focused on the extent of, and/or accuracy of media coverage. This is the first published study to examine systematically the language used by the United Kingdom (UK) popular press to specifically describe rheumatoid arthritis (RA).MethodsA patient and public involvement (PPI) approach, involving academics and service users with RA, was used to conduct the research. LexisNexis online repository of print media was searched for articles within a defined five year time frame, which included RA in the headline and/or lead paragraph of 15 UK national non-specialist newspapers. Resultant articles were uploaded to NVivo, and a realist perspective aided a thematic analysis of the data set.ResultsA search of LexisNexis produced 413 newspaper articles, of which 147 met the inclusion criteria. Three themes emerged: (1) language used to describe RA; (2) language used to refer to those who live with RA and; (3) language used to report on potential new treatments for RA. Negative and emotive terms such as ‘attack’, ‘painful’, ‘crippling’, and ‘agony’ were the most frequently used to describe the experience of RA. People diagnosed with RA were often portrayed as ‘sufferers’ or ‘victims’, though neutral language was also deployed. ‘Hope’ and ‘breakthrough’ were the most reported terms for potential new treatments for RA. Across the three themes, tabloid and middle market newspaper articles applied more sensationalised language with attention grabbing headlines and news stories. By contrast, such emotive terminology was less apparent in broadsheets.ConclusionsThe media is a source of information about RA for the general population, but the quality of newspaper journalism about the condition requires improvement. The findings may act as a stimulus for a national public awareness initiative and/or social marketing campaign. How the language currently constructed to describe RA in the press is received by people with RA would be an important area for future research.

Parasites in Rheumatoid Arthritis: Imminent Threat or Protective Effect?

Parasitic infections are among the oldest and most common infections in humans. Host defense alterations caused by autoimmune diseases or immunosuppressive drugs can cause modifications of the symptoms: indolent parasites can be reactivated, asymptomatic patients may experience new symptoms, or mild or moderate symptoms can become serious and, rarely, may lead to death. In recent years, new drugs have been used in the treatment of rheumatoid arthritis (RA), causing a greater level of immunosuppression and, therefore, more concerns regarding the risk of serious parasitic diseases. Of note, experimental studies have demonstrated that the immunomodulation induced by infection with helminths can minimize the occurrence and severity of rheumatoid arthritis. Products derived from helminths (such as glycoprotein ES-62) can exert favorable effects in RA patients via their anti-inflammatory actions. Greater knowledge of these substances may serve as a basis for the development of new treatments for RA. The full impact of parasitic diseases on patients with rheumatoid arthritis remains controversial, and further studies are warrented.

Prophylactic and therapeutic treatment with a synthetic analogue of a parasitic worm product prevents experimental arthritis and inhibits IL-1β production via NRF2-mediated counter-regulation of the inflammasome

Rheumatoid arthritis (RA) remains a debilitating autoimmune condition as many patients are refractory to existing conventional and biologic therapies, and hence successful development of novel treatments remains a critical requirement. Towards this, we now describe a synthetic drug-like small molecule analogue, SMA-12b, of an immunomodulatory parasitic worm product, ES-62, which acts both prophylactically and therapeutically against collagen-induced arthritis (CIA) in mice. Mechanistic analysis revealed that SMA-12b modifies the expression of a number of inflammatory response genes, particularly those associated with the inflammasome in mouse bone marrow-derived macrophages and indeed IL-1β was the most down-regulated gene. Consistent with this, IL-1β was significantly reduced in the joints of mice with CIA treated with SMA-12b. SMA-12b also increased the expression of a number of genes associated with anti-oxidant responses that are controlled by the transcription factor NRF2 and critically, was unable to inhibit expression of IL-1β by macrophages derived from the bone marrow of NRF2−/− mice. Collectively, these data suggest that SMA-12b could provide the basis of an entirely novel approach to fulfilling the urgent need for new treatments for RA.

RHEUMATOID ARTHRITIS AND PREGNANCY

Rheumatoid arthritis (RA) generally starts at the age when many women have already become mothers; however, it may occur in childhood or adolescence. Furthermore, there has been recently a women’s tendency to plan pregnacy for a more mature age, which necessitates a discussion about gestation in this disease. Investigation of mechanisms pregnancy can influence the development of RA both in the gestation and long-term periods is of important theoretical and practical value. The results of these investigations may be used to develop new treatments for RA and management tactics for patients during pregnancy and lactation. The aper gives the data available in the literature on fertility in RA, impact of pregnancy on its activity and that of RA on the course and outcomes of gestation, as well as current ideas on lactation and use of oral contraceptives in RA. Particular attention is given to drug therapy in pregnant and breastfeeding women with RA: groups of anti-rheumatic drugs are considered in detail in relation to the safety of or a potential risk from their use. A therapeutic algorithm and recommendations for pregnancy planning and a follow-up of patients with RA during gestation are proposed.

Inhibition of the insulin-like growth factor system is a potential therapy for rheumatoid arthritis

Objective: We have shown that connective tissue growth factor (CTGF) plays an important role in the pathogenesis of rheumatoid arthritis (RA). Insulin-like growth factor binding proteins (IGFBPs) are modules of CTGF. IGFBPs bind IGF-I and IGF-II. IGF-I plays a role in the regulation of immunity, bone metabolism and inflammation. Therefore, we investigated how the IGF system is associated with RA disease progression. Methods: Serum samples were collected from RA patients. IGF-I and IGFBP-3 production were evaluated by enzyme-linked immunosorbent assay, real-time RT-PCR and indirect immunofluorescence microscopy. Osteoclastogenesis was evaluated using tartrate-resistant acid phosphatase staining, a bone resorption assay and osteoclast-specific enzyme production. Angiogenesis was examined by a tube formation assay using human umbilical vein endothelial cells. Results: The serum concentrations of IGFBP-3 in RA patients were greater than those in normal controls. IGF-I and IGFBP-3 were produced primarily by macrophages in the RA synovium. Furthermore, tumor necrosis factor-α could induce aberrant IGF-I and IGFBP-3 production in synovial fibroblasts. IGF-I and IGFBP-3 promoted the induction of osteoclast generation and morphological changes, in combination with M-colony stimulating factor and the receptor activator of NF-κB ligand. In addition, IGF-I and IGFBP-3 induced angiogenesis, as determined by the tube formation assay. These effects were neutralized by anti-IGF-IR monoclonal antibody (mAb). Conclusions: These results indicate that aberrant IGF-I and IGFBP-3 production plays a role in abnormal osteoclastic activation and angiogenesis in RA. This work supports future clinical exploration of anti-IGF-IR mAb in drug repositioning as a new treatment for RA.

SP0137 Mirs in Activation of Myeloid Cells in RA

The development of new treatments for rheumatoid arthritis (RA) is limited by our incomplete understanding of disease pathogenesis. Particularly, those pathways mediating disease onset, failed repair, and the development of...

Clinical disease activity and acute phase reactant levels are discordant among patients with active rheumatoid arthritis: acute phase reactant levels contribute separately to predicting outcome at one year

IntroductionClinical trials of new treatments for rheumatoid arthritis (RA) typically require subjects to have an elevated acute phase reactant (APR), in addition to tender and swollen joints. However, despite the elevation of individual components of the Clinical Disease Activity Index (CDAI) (tender and swollen joint counts and patient and physician global assessment), some patients with active RA may have normal erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) levels and thus fail to meet entry criteria for clinical trials. We assessed the relationship between CDAI and APRs in the Consortium of Rheumatology Researchers of North America (CORRONA) registry by comparing baseline characteristics and one-year clinical outcomes of patients with active RA, grouped by baseline APR levels.MethodsThis was an observational study of 9,135 RA patients who had both ESR and CRP drawn and a visit at which CDAI was >2.8 (not in remission).ResultsOf 9,135 patients with active RA, 58% had neither elevated ESR nor CRP; only 16% had both elevated ESR and CRP and 26% had either ESR or CRP elevated. Among the 4,228 patients who had a one-year follow-up visit, both baseline and one-year follow-up modified Health Assessment Questionnaire (mHAQ) and CDAI scores were lowest for patients with active RA but with neither APR elevated; both mHAQ and CDAI scores increased sequentially with the increase in number of elevated APR levels at baseline. Each individual component of the CDAI followed the same trend, both at baseline and at one-year follow-up. The magnitude of improvement in both CDAI and mHAQ scores at one year was associated positively with the number of APRs elevated at baseline.ConclusionsIn a large United States registry of RA patients, APR levels often do not correlate with disease activity as measured by joint counts and global assessments. These data strongly suggest that it is appropriate to obtain both ESR and CRP from RA patients at the initial visit. Requiring an elevation in APR levels as a criterion for inclusion of RA patients in studies of experimental agents may exclude some patients with active disease.

Cell-Signaling Therapy in Rheumatoid Arthritis

New treatments for rheumatoid arthritis (RA) continue to emerge to meet unsatisfied needs of a significant number of patients. The development of new, oral biologic therapy is a significant step forward, although these drugs will require further evaluation in clinical settings before their true potential is appreciated. This new, oral biologic therapy has mostly focused on inhibition of intracellular signaling. These mechanisms and the available studies regarding the efficacy and safety of specific drugs which interfere with these mechanisms are the subject of this article.

Quantification of bone changes in a collagen-induced arthritis mouse model by reconstructed three dimensional micro-CT

BackgroundInflammatory arthritis is a chronic disease, resulting in synovitis and subchondral and bone area destruction, which can severely affect a patient’s quality of life. The most common form of inflammatory arthritis is rheumatoid arthritis (RA) in which many of the disease mechanisms are not well understood. The collagen-induced arthritis (CIA) mouse model is similar to RA as it exhibits joint space narrowing and bone erosion as well as involves inflammatory factors and cellular players that have been implicated in RA pathogenesis. Quantitative data for disease progression in RA models is difficult to obtain as serum blood markers may not always reflect disease state and physical disease indexes are subjective. Thus, it is important to develop tools to objectively assess disease progression in CIA.ResultsMicro-CT (Computed Tomography) is a relatively mature technology that has been used to track a variety of anatomical changes in small animals. In this study, micro-CT scans of several joints of control and CIA mice were acquired at 0, 4, 7, and 9 weeks after the immunization with collagen type II. Each micro-CT scan was analyzed by applying a segmentation algorithm to individual slices in each image set to provide 3-dimensional representations of specific bones including the humerus, femur, and tibia. From these representations, the volume and mean density of these bones were measured and compared. This analysis showed that both the volume and the density of each measured bone of the CIA mice were significantly smaller than those of the controls at week 7.ConclusionsThis study demonstrates that micro-CT can be used to quantify bone changes in the CIA mouse model as an alternative to disease index assessments. In conclusion, micro-CT could be useful as a non-invasive method to monitor the efficacy of new treatments for RA tested in small animals.

Why do we need new treatments for rheumatoid arthritis?

Rheumatoid arthritis is a chronic systemic autoimmune inflammatory disease characterized by progressive joint damage. The classical treatments of the disease such as myocrisin and sulphasalazine, are not always effective at controlling the disease. This has necessitated the development of novel agents for treating rheumatoid arthritis. Most of these drugs are biological in nature and are targeted at specific sites of the inflammatory cascade of reactions. A number of clinical trials have been conducted. The clinical effects that have been observed are transient, necessitating repeated treatments and the risk of vaccination effects. Many of these agents have to be administered parenterally, production costs are very high. Consequently, chemical entities which can be taken orally need to be developed. Since the immune system is very complex with pleiotropic cytokines and redundancy in some of the regulatory networks, it may therefore be necessary to use multiple agents targeted at different specific sites of the inflammatory cascade or that different agents could be given at different stages of the disease, to induce disease remission and maintain the response to therapy. Cytokines such as tumour necrosis factor (TNF) and interleukin 1 (IL-1) play important physiological roles in the host's defence systems against infections and malignancy. The chronic inhibition of these cytokines by targeted therapies may therefore lead to the development of side effects. Thus, carefully controlled long-term studies will be required to assess the safety of selective targeting of processes involved in inflammation. A more recent novel approach is to target hypoxic tissues with bioreductive agents. Thus, some of the established rheumatoid arthritis treatments could be linked to bioreductive agents and released in hypoxic tissues where inflammation is occurring. This review summarizes the important developments in the therapy of rheumatoid arthritis. There is no doubt that despite these developments we need to develop new and advanced treatment modalities for rheumatoid arthritis.

Therapeutic applications of monoclonal antibodies

Monoclonal antibodies drive the development of multibillion dollar biotechnology industry. Many of the pharmaceuticals companies have entered monoclonal antibodies sector, attracted by quicker and less costly development, higher success rates, premium pricing, and potentially reduced threats from generics. The ideal treatment of rheumatoid arthritis (RA) should be safe, produce sustained disease remission and stop radiological damage after a brief course of treatment. If repeated treatments are necessary, they must be safe and economical to use in the long term. It is against these criteria that new treatments for RA, including mAb, should and will be assessed. Monoclonal antibodies are used in the treatment of cancer, including leukemia, colorectal cancer, breast cancer and non-Hodgkin’s lymphoma, RA, ischemic heart disease and transplant rejection. How to Cite this Article Pubmed Style Prajapati DS, Shah JS, Dave JB, Patel CN. Applications of Monoclonal SRP. 2011; 2(1): 37-42. doi:10.4103/0975-8453.83437 Web Style Prajapati DS, Shah JS, Dave JB, Patel CN. Applications of Monoclonal http://www.sysrevpharm.org/?mno=302644609 [Access: March 28, 2021]. doi:10.4103/0975-8453.83437 AMA (American Medical Association) Style Prajapati DS, Shah JS, Dave JB, Patel CN. Applications of Monoclonal SRP. 2011; 2(1): 37-42. doi:10.4103/0975-8453.83437 Vancouver/ICMJE Style Prajapati DS, Shah JS, Dave JB, Patel CN. Applications of Monoclonal SRP. (2011), [cited March 28, 2021]; 2(1): 37-42. doi:10.4103/0975-8453.83437 Harvard Style Prajapati DS, Shah JS, Dave JB, Patel CN (2011) Applications of Monoclonal SRP, 2 (1), 37-42. doi:10.4103/0975-8453.83437 Turabian Style Prajapati DS, Shah JS, Dave JB, Patel CN. 2011. Applications of Monoclonal Systematic Reviews in Pharmacy, 2 (1), 37-42. doi:10.4103/0975-8453.83437 Chicago Style Prajapati DS, Shah JS, Dave JB, Patel CN. Therapeutic Applications of Monoclonal Antibodies. Systematic Reviews in Pharmacy 2 (2011), 37-42. doi:10.4103/0975-8453.83437 MLA (The Modern Language Association) Style Prajapati DS, Shah JS, Dave JB, Patel CN. Therapeutic Applications of Monoclonal Antibodies. Systematic Reviews in Pharmacy 2.1 (2011), 37-42. Print. doi:10.4103/0975-8453.83437 APA (American Psychological Association) Style Prajapati DS, Shah JS, Dave JB, Patel CN (2011) Applications of Monoclonal Systematic Reviews in Pharmacy, 2 (1), 37-42. doi:10.4103/0975-8453.83437

In vivo fluorescence imaging of E‐selectin: Quantitative detection of endothelial activation in a mouse model of arthritis

In vivo optical imaging can delineate at the macroscopic level processes that are occurring at the cellular and molecular levels. E-selectin, a leukocyte adhesion molecule expressed on endothelium, is induced by tumor necrosis factor α (TNFα) and other cytokines involved in the pathogenesis of rheumatoid arthritis (RA). Collagen-induced arthritis (CIA) in mice is widely used to study the disease mechanisms and identify new treatments for RA. The purpose of this study was to demonstrate E-selectin-targeted fluorescence imaging in vivo in a mouse model of paw edema generated by local injection of TNFα as well as in mice with CIA. Animals with either CIA or TNFα-induced paw edema were injected with anti-E-selectin or control antibodies labeled with a DyLight 750-nm near-infrared (NIR) probe. In vivo imaging studies were undertaken using an NIR optical imaging system, and images were coregistered with plain radiographic images. The mean fluorescence intensity measured over the time-course of TNFα-induced edema demonstrated a 1.97-fold increase (P<0.001) in signal in inflamed paws at 8 hours following injection of anti-E-selectin antibody, as compared to that in the isotype control. In the CIA model, a 2.34-fold increase in E-selectin-targeted signal was demonstrated (P<0.01). Furthermore, significant E-selectin-targeted signal was observed in the paws of animals immunized with collagen that did not display overt signs of arthritis. E-selectin-targeted fluorescence in vivo imaging is a quantifiable method of detecting endothelial activation in arthritis and can potentially be applied to the quantification of disease and the investigation of the effects of new therapies. Importantly, this approach may also be useful for the detection of subclinical disease in RA.

Missing a link

New treatments for rheumatoid arthritis might be behind the increase in listeriosis in older people.