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ID PMID Title PublicationDate abstract
34742322 An alcohol extract prepared from the male flower of Eucommia ulmoides Oliv. promotes synov 2021 Nov 6 BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease dominated by synovial hyperplasia and bone destruction. The male flower of Eucommia ulmoides Oliv. (EF) has been shown to exert effects on the inflammation caused by RA. However, how EF affects synoviocyte apoptosis and bone destruction on RA have not been investigated thoroughly. The effects of EF on apoptosis of human fibroblast-like synoviocytes-rheumatoid arthritis (HFLS-RA) cells, osteoclast differentiation of RAW264.7 cells, and bone destruction in a collagen-induced arthritis (CIA) model in rats were explored. METHODS: First, the main components of EF were identified by high-performance liquid chromatography. In vitro, we investigated the anti-proliferative and pro-apoptotic effects of EF on HFLS-RA cells by immunofluorescence assays, flow cytometry, real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blotting; we also investigated how EF influenced the differentiation of RAW264.7 cells into osteoclasts. In vivo, we used a rat model of CIA to investigate the effects of EF on anti-arthritis activity, toe swelling, Arthritis Score, serum levels of metabolic bone factors, and pathologic conditions. Micro-computed tomography was used to scan ankle joints. mRNA and protein expression of factors related to the nuclear factor-kappa B (NF-κB) pathway were determined by RT-qPCR and western blotting, respectively. RESULTS: EF inhibited synoviocyte proliferation and promoted apoptosis in a dose-dependent manner. EF inhibited osteoclast differentiation by inhibiting activation of the NF-κB pathway. EF reduced articular inflammation in CIA rats, inhibited the expression of pro-angiogenic factors, and delayed the destruction of articular cartilage and bone. Our data indicated that EF acted via a mechanism related to bone metabolism induced by the NF-κB pathway. CONCLUSIONS: EF exerts a potential therapeutic effect upon RA. Our research will help to elucidate the potential pharmacologic mechanisms associated with the beneficial effects of EF, and provide an experimental basis for EF application in clinical treatments.
34538950 Bone-sparing effects of rituximab and body composition analysis in a cohort of postmenopau 2021 OBJECTIVE: Osteoporosis is the most common bone tissue disease and it is characterized by a reduced bone mineral density (BMD). The main physiopathological mechanisms converge on the uncoupling between bone formation and resorption, thus leading to an enhanced risk of fractures. Several papers have documented the inverse relationships linking high inflammatory cytokines, anti-citrullinated protein antibodies, rheumatoid factor, and BMD in rheumatoid arthritis (RA). Rituximab (RTX) is a chimeric monoclonal antibody directed against the CD20 receptor of B cells. Since the Food and Drug Administration approved it for RA in 2006, there have been many clinical experiences regarding its use. Nevertheless, few studies evaluate the effect of rituximab on BMD. RA is a disease characterized by immune dysfunction with high levels of inflammatory cytokines, autoantibodies, and it is reasonable that a B cell depleting therapy could restore a physiological cytokine balance, thus exerting an osteoprotective effect on the bone tissue. The purpose of this paper is to highlight any difference in BMD and to assess differences in body composition over a retrospective 18-month follow-up period after RTX treatment with a B cell depleting therapy. MATERIAL AND METHODS: We analyzed by dual energy X-ray absorptiometry BMD expressed as g/cm(2) and body composition modifications over 18 months with RTX treatment of 20 postmenopausal RA patients. RESULTS: After eighteen months of therapy with RTX, a statistically significant increase in vertebral (L1-L4) BMD and the stability of femoral BMD were documented. CONCLUSIONS: Rituximab is associated with an improvement of vertebral and preservation of femoral BMD, suggesting a bone-sparing effect due to B cell depletion. Furthermore, patients displayed a redistribution of fat masses toward the hip region.
34919045 Severity of COVID-19 infection in primary Sjögren's syndrome and the emerging evidence of 2021 Nov Since the beginning of the COVID-19 disease pandemic caused by the new coronavirus SARS-CoV-2, the disease has claimed over 205M cases (205,338,159) and 4,333,094 deaths (WHO dashboard - accessed 15/08/2021). In addition to the overwhelming impact on healthcare systems treating acutely ill patients, the pandemic has had an impact on all other aspects of health care delivery, including the management of chronic diseases, the risk that is posed in patients with chronic conditions and the risk of the infection itself in those with chronic conditions. Autoimmune rheumatic diseases (ARDs), including primary Sjögren's syndrome (pSS), characterised by immune dysregulation affecting several organs in variable severity, have been of particular interest given the accelerated phase of the immune response in the course of SARS-CoV-2 infection leading to the acute inflammatory response and respiratory distress syndrome or multi-organ failure. On the other hand, the effect of immunosuppressive drug therapies can represent a double edge sword on the course of the disease, either by increased susceptibility to and severity of the infection, or by preventing the accelerated inflammatory response induced by the infection. Additionally, the long-term impact of SARS-CoV-2 infection on the host immune system has led to the onset of novel complex clinical manifestations, comprised under the large umbrella of "long-COVID", which we are only starting to understand. In this review we focus on two interrelated aspects: i) the impact of COVID-19 on patients with pSS and ii) the emerging evidence of long-term xerostomia after SARS-CoV-2 infection.
34953198 [Sjogren's disease/syndrome in combination with autoimmune liver damage. 20-years observat 2021 Sjogren's disease (BS) is a systemic autoimmune disease, the main symptoms of which are associated with dry eyes, mouth, skin, respiratory and gastrointestinal tract, etc., but there are a large number of extra-vascular symptoms that can accompany this disease: weakness, swelling of the lymph nodes, respiratory failure, pain and swelling of the joints, rash, dysphagia, gastro-esophageal reflux, lymphoma, etc. In addition, the etiology of this disease remains unknown, and the pathogenesis is partially studied. The diagnosis of Sjogren's disease is complicated by a variety of clinical manifestations, as well as subacute and chronic variants of the course of the disease, in addition, the diagnostic criteria are periodically changed. It is recommended to adhere to the domestic diagnostic criteria considering the presence of laboratory signs of an autoimmune disease. The article presents a clinical observation of a patient with the development of the main symptoms and signs of BS and autoimmune hepatitis for 20 years. Recurrent mumps or chronic bilateral enlargement of the parotid salivary glands may be the first symptom of Sjogren's disease, which is recommended to extend the examination in order to identify other, sometimes latent signs of the disease.
32990106 Clinical features of elderly-onset Adult-onset Still's disease. 2021 Jul OBJECTIVES: To clarify the characteristics of patients with elderly-onset Adult-onset Still's disease (AOSD). METHODS: Patients were classified into elderly-onset (>60 years: 47 patients) and younger-onset (≤60 years: 95 patients) groups according to their age at diagnosis of AOSD. Clinical features, treatments, and prognosis were compared between the elderly-onset and younger-onset groups. RESULTS: In the elderly-onset group, compared with the younger-onset group, typical skin rashes were less frequent (21.3% vs 58.9%, respectively; p < .0001), whereas pleuritis (27.7% vs 7.4%, respectively; p = .0011) and disseminated intravascular coagulation (19.1% vs 2.1%, respectively; p = .0004) were more frequent, and serum ferritin levels were higher (median 12,700 ng/ml vs 2526 ng/ml, respectively; p < .0001). Overall survival and AOSD-related survival were reduced (p = .0006 and p = .0023, respectively) and drug-free remission was less frequent (p = .0035) in the elderly-onset group compared with the younger-onset group. CONCLUSIONS: Our results demonstrated that elderly-onset AOSD patients had several characteristics that differed from younger-onset AOSD patients, including less typical skin lesions, more AOSD-related complications, higher ferritin levels, and poorer prognoses.
34128808 Dual effects of interleukin-10 on natural killer cells and monocytes and the implications 2021 Sep OBJECTIVES: We compared the serum levels of multiple cytokines in patients with adult-onset Still's disease (AOSD) and healthy controls to assess the effects of humoral factors on natural killer (NK) cells and monocytes. METHODS: We quantified the serum levels of 10 cytokines in the patients using bead-based multiplex immunoassays, along with interleukin (IL-)18 using ELISA. We then sorted NK cells and monocytes from the peripheral blood mononuclear cells (PBMCs) of healthy volunteers, cultured them in the presence or absence of cytokines that were detected in some or all of the serum samples from the AOSD patients and their combinations in vitro, and analysed the culture supernatant. RESULTS: IL-6 and IL-18 were the main cytokines increased in the serum of AOSD patients. When NK cells were cultured with the cytokines and IL-10, the combination of IL-10 and IL-18 substantially induced interferon (IFN-)γ. IL-6 had little effect on NK cells, probably because they barely expressed the IL-6 receptor and glycoprotein 130 (gp130). IFN-γ induced monocytes to produce IL-1β, IL-6 and tumour necrosis factor (TNF-)α whereas IL-10 inhibited the induction of these proinflammatory cytokines. CONCLUSIONS: IL-10 evidently has dual effects on NK cells (stimulation) and on monocytes (inhibition). Better understanding the roles of the cytokine network would shed light on the pathogenesis of AOSD.
34219641 [Xerostomia]. 2021 Jul 5 Xerostomia and salivary gland hypofunction impact oral health and quality of life and are mainly caused by the intake of medications, chronic disorders like Sjögren's syndrome, and head and neck radiation. Other aetiologies may be local diseases of the salivary glands including infections, cancer, or obstructive diseases of the salivary ducts. Management strategies are primarily alleviating symptoms. Current investigations show promising results in stem cell treatment. In this review, we want to provide comprehension of the aetiologies, evaluation, and management of xerostomia and hyposalivation.
33556412 Risk of macrophage activation syndrome in patients with adult-onset Still's disease with s 2021 Dec BACKGROUND: Small case series and case reports indicated that atypical persistent pruritic eruptions (PPEs), another type of skin lesions seen in adult-onset Still's disease (AOSD), imply a worse prognosis than typical evanescent rashes. OBJECTIVE: To investigate clinical characteristics and macrophage activation syndrome (MAS) occurrence in AOSD with PPEs. METHODS: A retrospective cohort study analyzed 150 patients with AOSD with rashes at the First Affiliated Hospital of Zhejiang University from January 2013 to December 2019. RESULTS: Patients with AOSD with PPEs had higher lactate dehydrogenase (492.00 U/L vs 382.00 U/L; P < .001) and ferritin (6944.10 ng/ml vs 4286.60 ng/ml; P = .033), and lower fibrinogen (5.05 g/L vs 5.77 g/L; P = .014) than those with evanescent rashes. Patients with AOSD with PPEs had a higher incidence (17.4% vs 3.1%, P = .006) and cumulative event rate for MAS (P = .008) and tended to receive high-dose glucocorticoid (36% vs 20.3%; P = .036). Multivariate analysis indicated that PPEs (hazard ratio [HR], 5.519; 95% confidence interval [CI], 1.138-26.767; P = .034), aspartate aminotransferase of greater than 120 U/L (HR, 8.084; 95% CI, 1.728-37.826; P = .008), and splenomegaly (HR, 21.152; 95% CI, 2.263-197.711; P = .007) were independent risk factors for MAS. LIMITATIONS: Single-center, retrospective nature, small sample size. CONCLUSION: PPEs indicated increased severity and MAS occurrence versus evanescent rashes. PPEs, aspartate aminotransferase of greater than 120 U/L, and splenomegaly were risk factors for MAS in AOSD with skin involvement.
34797392 A flare of Still's disease following COVID-19 vaccination in a 34-year-old patient. 2022 Apr Vaccination is a cornerstone for reducing the risk of COVID-19 infection during a pandemic. Although the currently used COVID-19 vaccine is considered safe, some concerns persist regarding the likelihood of flares of rheumatic diseases. Still's disease is a rare auto-inflammatory disorder of unknown etiology, and the data on the flare of Still's disease following COVID-19 vaccination are limited. Therefore, we hereby present the case of a 34-year-old female patient with Still's disease who experienced a flare after a ChAdOx1 nCoV-19 vaccination. The patient visited the emergency department complaining of fever, arthralgia, myalgia, pleuritic chest pain and macular salmon-pink rash on her back for the past 2 days. She had maintained low Still's disease activity with etanercept and low-dose glucocorticoid for 14 years. She received the ChAdOx1 nCoV-19 vaccine 7 days before the flare. Laboratory investigations revealed leucocytosis and elevated serum levels of erythrocyte sedimentation rate, C-reactive protein, and ferritin. Computed tomography showed no specific findings. She received methylprednisolone pulse therapy, etanercept, and methotrexate for treating the Still's disease flare. However, her symptoms were not fully controlled, and she developed pericarditis, pleuritis, fever and macular rashes expanding to her extremities. After excluding infectious conditions by blood culture and pleural fluid analysis, we administered tocilizumab with methotrexate and prednisolone. Her symptoms and laboratory findings improved significantly, and she was discharged without symptoms 7 days later. Although rare, this case of a patient with Still's disease undergoing a flare following vaccination suggests that close observation of disease activity is warranted following COVID-19 vaccination.
34100163 Coincident Kikuchi-Fujimoto's disease and adult-onset Still's disease: report of a patient 2021 Dec Kikuchi-Fujimoto's disease (KFD) and adult-onset Still's disease (AOSD) are rare idiopathic inflammatory conditions of unknown etiology. Ten prior instances of KFD and AOSD occurring together have been reported in the medical literature. These overlaps, together with certain distinguishing clinical and laboratory characteristics in these co-occurrences, offer insight into the pathophysiology of both of these rare disorders. Too, examination of these cases may help improve the diagnostic evaluation and care of patients afflicted with these rare diseases. We therefore report an additional patient with KFD and AOSD occurring in a middle-aged Hispanic female patient and perform a systematic literature review using the PubMed/MEDLINE and Embase databases to further analyze and compare prior identified cases. Our observations in our index case complement and expand previous reports, including new demographic and diagnostic features not seen in prior cases of overlap. Indeed ours is the first in a patient of Hispanic ethnicity, with retroperitoneal lymphadenopathy, as well as with a skin biopsy consistent with AOSD. Each of the reviewed cases of co-occurrence met the diagnostic criteria for both KFD and AOSD. This finding, in the setting of unique clinical and diagnostic manifestations that are not typically seen in either disease entity alone, suggests the presence of an overlap syndrome. Also, many of the shared clinical features and symptomatic responses to targeted therapies implies a similar, yet still poorly understood, pathophysiologic pathway for the two diseases.
34839178 Advances in understanding N-glycosylation structure, function, and regulation in health an 2021 Sep N-linked glycosylation is a post-translational modification crucial for membrane protein folding, stability and other cellular functions. Alteration of membrane protein N-glycans is implicated in wide range of pathological conditions including cancer metastasis, chronic inflammatory diseases, and viral pathogenesis. Even though the roles of N-glycans have been studied extensively, our knowledge of their mechanisms remains unclear due to the lack of detailed structural analysis of the N-glycome. Mapping the N-glycome landscape will open new avenues to explore disease mechanisms and identify novel therapeutic targets. This review discusses the diverse structure of N-linked glycans, the function and regulation of N-glycosylation in health and disease, and ends with a focus on recent approaches to target N-glycans in rheumatoid arthritis and cancer metastasis.
34874834 One year in review 2021: Sjögren's syndrome. 2021 Nov Sjögren's syndrome (SS) is a multifactorial systemic autoimmune disease of unknown aetiology characterised by a wide spectrum of different clinical manifestations and scattered complications. Recently, great efforts have been made to elucidate mechanisms involved in the pathogenesis of the disease in order to identify exploitable therapeutic targets in SS. Similarly, novel insights have enabled to better define disease phenotypes and different outcomes. Ultimately, the discovery of new potential therapeutic targets and a better stratification of patients are paving new avenues for novel treatment options and treat-to-target therapeutic approach. In this review, we will provide a critical digest of the recent literature published in 2020 on SS pathogenesis, clinical manifestations and novel treatment options.
34378522 [Sjögren's syndrome]. 2021 Aug 2 Sjögren's syndrome (SS) is a common autoimmune disease with a prevalence of 1%. SS affects primarily women between the age of 30 and 50 years. The classic manifestations are sicca symptoms, musculoskeletal pain and fatigue but the disease can affect all organs. SS is associated with the antibody anti-SSA antibodies. The patients have a 15-20 times higher risk of lymphoma and an increased risk of spontaneous abortion and AV-block in life-born children. In this review, we share the diagnostic process and risk stratification and outline the treatments available from private practice.
34378080 Rescued from desperation: adult-onset Still's disease with life-threatening interstitial l 2022 May This article presents a case of fulminant interstitial lung disease (ILD) with macrophage activation syndrome (MAS) as a rare complication of adult-onset Still's disease in a 43-year-old male patient. Initial presentation showed severe ILD. Early treatment focused on high-dose corticosteroids; however, disease remission could not be achieved. After an additional inflammatory focus and underlying malignancy were excluded, the triad of pancytopenia, fever, and high ferritin levels indicated MAS; bone marrow biopsy confirmed secondary hemophagocytic histiocytosis. Treatment with tocilizumab induced fast and effective therapeutic success.
34024355 An Unusual Presentation of Adult-Onset Still's Disease in a Patient with Recurrent Pleural 2021 May Adult-Onset Still's Disease (AOSD) usually presents with a salmon-colored skin rash and arthralgias. However, it can also be present with pleural and pericardial effusions. These effusions are often misdiagnosed as having an infectious etiology because AOSD usually present with fever, leukocytosis, elevated inflammatory markers, procalcitonin and CRP. There is usually a delay in giving steroids until the exclusion of all infectious etiologies, including extensive workups. Herein, we present a case report of AOSD in a patient with recurrent pleural and pericardial effusions, with no skin rashes or joint pain. Patient initially presented with fever, pleural and pericardial effusions, which was then treated as pneumonia with parapneumonic effusions. Patient returned for the second time with shortness of breath, productive cough, and fever, with no resolutions of pleural and pericardial effusions. Patient was found to have an extremely high ferritin levels, whereby a diagnosis of AOSD was made after excluding infection, malignancy and other rheumatological disorders based on the Yamaguchi criteria. AOSD is a rare disease with unusual presentation and diagnosis is often delayed. This case aimed to raise awareness among physicians of the multifaceted presentation of AOSD.
34919044 Influence of the age at diagnosis in the disease expression of primary Sjögren syndrome. 2021 Nov OBJECTIVES: To analyse how the main components of the disease phenotype (sicca symptoms, diagnostic tests, immunological markers and systemic disease) can be driven by the age at diagnosis of primary Sjögren's syndrome (pSS). METHODS: By January 2021, the participant centres had included 12,753 patients from 25 countries that fulfilled the 2002/2016 classification criteria for pSS. The age at diagnosis was defined as the time when the attending physician confirmed fulfilment of the criteria. Patients were clustered according to age at diagnosis. 50 clusters with more than 100 observations (from 27 to 76 years) were used to study the influence of the age at diagnosis in the disease expression. RESULTS: There was a consistent increase in the frequency of oral dryness according to the age at diagnosis, with a frequency of <90% in patients diagnosed at the youngest ages and >95% in those diagnosed at the oldest ages. The smooth curves that best fitted a linear model were the frequency of dry mouth (adjusted R2 0.87) and the frequency of abnormal oral tests (adjusted R2 0.72). Therefore, for each 1-year increase in the age at diagnosis, the frequency of dry mouth increased by 0.13%, and the frequency of abnormal oral diagnostic tests by 0.11%. There was a consistent year-by-year decrease in the frequency of all autoantibodies and immunological markers except for cryoglobulins. According to the linear models, for each 1-year increase in the age at diagnosis, the frequency of a positive result decreased by 0.57% (for anti-Ro antibodies), 0.47% (for RF) and 0.42% (for anti-La antibodies). The ESSDAI domains which showed a more consistent decrease were glandular and lymph node involvement (for each 1-year increase in the age at diagnosis, the frequency of activity decreased by 0.18%), and constitutional, cutaneous, and haematological involvements (the frequency decreased by 0.09% for each 1-year increase). In contrast, other domains showed an ascending pattern, especially pulmonary involvement (for each 1-year increase in the age at diagnosis, the frequency of activity increased by 0.22%), and peripheral nerve involvement (the frequency increased by 0.09% for each 1-year increase). CONCLUSIONS: The influence of the age at diagnosis on the key phenotypic features of pSS is strong, and should be considered critical not only for designing a personalised diagnostic approach, but also to be carefully considered when analysing the results of diagnostic tests and immunological parameters, and when internal organ involvement is suspected at diagnosis.
34796851 Development and performance of the Clinical Trials ESSDAI (ClinTrialsESSDAI), consisting o 2021 Nov OBJECTIVES: To develop and evaluate the Clinical Trials EULAR Sjögren's Syndrome Disease Activity Index (ClinTrialsESSDAI), consisting of frequently active clinical domains of the ESSDAI, using two randomised controlled trials in primary Sjögren's syndrome (pSS). METHODS: The ASAP-III trial in abatacept (80 pSS patients) and TRACTISS trial in rituximab (133 pSS patients) were analysed. The most frequently active clinical domains were selected, and ClinTrialsESSDAI total score was calculated using existing weightings of the ClinESSDAI (which also excludes the biological domain). Performance of the ClinTrialsESSDAI was compared to ClinESSDAI and ESSDAI. Responsiveness was assessed using standardised response mean (SRM), and discrimination was assessed using adjusted mean difference. RESULTS: Besides the biological domain, the most frequently active domains were glandular, articular, haematological, constitutional, lymphadenopathy and cutaneous. These domains were selected for the ClinTrialsESSDAI. At primary endpoint visits, SRM values of ClinTrialsESSDAI, ClinESSDAI and ESSDAI were respectively -0.65/-0.59, -0.63/-0.59 and -0.64/-0.61 for abatacept/placebo and -0.33/-0.13, -0.34/-0.12 and -0.41/-0.16 for rituximab/placebo. Adjusted mean differences between active treatment and placebo groups were respectively -1.7, -1.4 and -1.1 for ASAP-III and -1.1, -1.1 and -1.2 for TRACTISS. CONCLUSIONS: The ClinTrialsESSDAI, consisting of six frequently active clinical domains of the ESSDAI, shows closely similar responsiveness and discrimination between treatment groups compared to the ClinESSDAI and ESSDAI. Therefore, this ClinTrialsESSDAI is not preferable to ClinESSDAI and ESSDAI for use as primary endpoint. A composite endpoint combining response at multiple clinically relevant items seems more suitable as primary study endpoint in pSS.
34711620 Adult-onset Still's disease after environmental exposure while working in Africa. 2021 Oct 28 Adult-onset Still's disease (AOSD) is characterised by a constellation of systemic inflammatory symptoms and typical laboratory findings like hyperferritinaemia. A high index of suspicion is needed to identify patients as diagnosis is primarily clinical and significant morbidity can result from delayed diagnosis. While AOSD may be self-limited, some patients experience flares over years and require more aggressive treatment approaches. Aetiology is unknown but can be triggered by viral infections and other environmental factors in a susceptible genetic host. We present a case of AOSD triggered after exposure to a sap-like liquid while working in Africa. This inciting event occurred as part of a hostile act towards the patient and involved medicinal practices traditional to the area. Our case highlights the more chronic course of AOSD, which requires escalating biological treatment to avoid long-term corticosteroids, as well as the juncture between traditional and modern medical practices.
32856968 Clinical practice guidance for Sjögren's syndrome in pediatric patients (2018) - summariz 2021 Mar There are a considerable number of pediatric patients with Sjögren's syndrome (SS); however, SS is generally considered rare among children. Pediatric patients with SS report fewer sicca symptoms; therefore, many are under-diagnosed and cannot access appropriate medical management. Therefore, we propose a newly developed guidance for the diagnosis, treatment, and management of pediatric SS, including epidemiology, clinical features, and diagnostic examination methodology. The aim of this guidance was to standardize the medical care of pediatric SS in Japan, and we published the Japanese version by YODOSHA in 2018. This article is the English version, which is summarized and updated. This guidance will need to be revised in the near future as additional clinical data become available.
35069822 Synergistic effect of Bruton's tyrosine kinase and TNF-α in the regulation of rheumatoid 2022 Feb The presence of Bruton's tyrosine kinase (BTK) in macrophages has been recommended as a promising therapeutic target for rheumatoid arthritis (RA). In addition, activated macrophages in the inflamed joints of patients with RA can also produce a plethora of cytokines, such as TNF-α. The aim of the present study was to investigate the potential role of BTK and TNF-α in the regulation of RA. The results demonstrated that higher levels of BTK and TNF-α were observed in macrophages in inflamed RA joints compared with those in normal joint tissues. Subsequently, the role of BTK and TNF-α in the regulation of cellular process in inflammatory macrophages was analyzed. It was demonstrated that aberrant expression of BTK and TNF-α in inflammatory macrophages can lead to higher cell proliferation rates. Once the expression of BTK or TNF-α was restricted by using short interfering (si)RNAs (siBTK or siTNF-α), the activity of inflammatory macrophages was significantly downregulated. Of note, when the expression of BTK and TNF-α was simultaneously decreased, the proliferation rate of inflammatory macrophages was inhibited to the greatest extent. Subsequently, the underlying mechanisms through which BTK and TNF-α can regulate RA were investigated. The results demonstrated that BTK mainly regulated the ERK/JNK pathway, while TNF-α mainly affected the inactive rhomboid protein 2/B-cell-activating factor pathway. Finally, animal experiments demonstrated that simultaneous silencing of both BTK and TNF-α can significantly alleviate the symptoms associated with RA.