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ID PMID Title PublicationDate abstract
22930883 Drug therapy of inflammatory arthritis. 2012 Aug Inflammatory arthritis involves a diverse range of conditions in which an uncontrolled immune response occurs. A number of advances in assessment, diagnosis and treatment have been made in recent years. Drug therapies used in inflammatory arthritis aim to reduce symptoms and suppress inflammation, joint damage and disability. In rheumatoid arthritis (RA), immunosuppression is used in almost all patients, with an emphasis on early aggressive treatment to achieve clinical remission. This approach is less successful in spondylarthropathies, for which non-steroidal anti-inflammatory drugs remain first-line therapy. The use of biologic therapies has increased dramatically across a range of indications and has resulted in improved outcomes for patients. These agents are associated with an increased risk of infection, particularly tuberculosis in patients receiving tumour necrosis factor inhibitors. Alternative biologics have entered clinical practice for RA in recent years, and clinical trials using these agents, as well as novel non-biologic therapies, are in progress for RA and other conditions.
21614629 ["Memories of my sick hands": life and medical history of the painter Alexej von Jawlensky 2011 Jun Alexej von Jawlensky (1864-1941), one of the most important expressionist painters and a member the artist group "The Blue Four", suffered from severe rheumatoid arthritis. He was the first painter in the twentieth century to create extensive series of paintings especially of human faces. The medical history of Jawlensky as documented in his letters, is a harrowing document of a great artist who suffered from rheumatoid arthritis at a time when medical treatment was limited to physical therapy, pain medication and other relatively ineffective modalities, including the unnecessary extraction of teeth. Jawlensky's disease was characterized by a rapidly progressive course with severe pain, rapid onset of disability and ending up with complete immobilization and paralysis for several years until his death.The artistic processing and sublimation of his illness and suffering resulting in a series of over 1,000 small format meditations are the impressive and touching example of creative coping with rheumatoid arthritis. The meditations are unique in the history of art and often compared with icons. However, knowing the medical condition of Jawlensky these paintings can also be seen as metaphors of suffering and in each image the great physical and mental effort is reflected in the artistic details. Therefore, his art agent Galka E. Scheyer formulated in a letter to him: "You are the painter of the human soul. I know of no other modern painter of the human soul."
22612502 JAK inhibition for the treatment of rheumatoid arthritis: a new era in oral DMARD therapy. 2012 Jul INTRODUCTION: In rheumatoid arthritis (RA) there is a significant medical need for safe and effective oral disease-modifying anti-rheumatic drugs (DMARDs) for patients who respond inadequately to methotrexate, the first-line therapy in RA. Oral agents targeting Janus-associated kinases (JAKs) are the most promising new agents in clinical development. This review describes the preclinical and clinical activities of the most advanced JAK inhibitors with different JAK selectivity profiles. AREAS COVERED: This review first describes the current treatment landscape and the pathophysiology of RA. Role for cytokines in the disease pathogenesis followed by significance of JAK/STAT pathway in cytokine signaling are discussed. Available chemical description and enzymatic data on the most advanced JAK inhibitors in clinical development are provided. Preclinical and clinical results that are publicly available are summarized. Review of literature was conducted using National Library of Medicine (NLM) database, 'PubMed'. In addition, all publicly disclosed data from companies that are developing the JAK inhibitors was researched to obtain the most up-to-date information of the compounds discussed in this report. EXPERT OPINION: Emerging clinical results demonstrate that JAK inhibition is a validated new mechanism for the development of oral DMARD agents that is likely to join the armamentarium against RA in the near future.
22493511 Quantitative proteomic analysis of eight cartilaginous tissues reveals characteristic diff 2012 Jun 1 Human synovial joints display a characteristic anatomic distribution of arthritis, e.g. rheumatoid arthritis primarily affects the metacarpophalangeal and proximal finger joints, but rarely the distal finger joints, whereas osteoarthritis occurs in the distal and proximal finger joints. Pelvospondylitis has a selective localization to the spine and sacroiliac joints. Is this tropism due to differences between the cartilages at the molecular level? To substantiate this concept the present study provides a background detailed compositional analysis by relative quantification of extracellular matrix proteins in articular cartilages, meniscus, intervertebral disc, rib, and tracheal cartilages on samples from 5-6 different individuals using an optimized approach for proteomics. Tissue extraction followed by trypsin digestion and two-dimensional LC separations coupled to tandem mass spectrometry, relative quantification with isobaric labeling, iTRAQ(TM), was used to compare the relative abundance of about 150 proteins. There were clear differences in protein patterns between different kinds of cartilages. Matrilin-1 and epiphycan were specific for rib and trachea, whereas asporin was particularly abundant in the meniscus. Interestingly, lubricin was prominent in the intervertebral disc, especially in the nucleus pulposus. Fibromodulin and lumican showed distributions that were mirror images of one other. Analyses of the insoluble residues from guanidine extraction revealed that a fraction of several proteins remained unextracted, e.g. asporin, CILP, and COMP, indicating cross-linking. Distinct differences in protein patterns may relate to different tissue mechanical properties, and to the intriguing tropism in different patterns of joint pathology.
22089466 Mortality risk by functional status and health-related quality of life in patients with rh 2012 Jan OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of death. Modern RA therapy has been shown to improve health status, but the relationship of such improvements to mortality risk is unknown. We assessed the relationship between health status and all-cause mortality in patients with RA, using the Health Assessment Questionnaire (HAQ) and the Medical Outcomes Study Short Form-36 questionnaire (SF-36) physical and mental component summary scores (PCS, MCS). METHODS: Subjects (n = 10,319) were selected from the National Data Bank for Rheumatic Diseases, a prospective longitudinal observational US study with semiannual assessments of HAQ, PCS, and MCS. Risk of death up to 7 years through 2006 was obtained from the US National Death Index. Relationship of HAQ, PCS, and MCS to mortality was assessed using Cox regression models; prediction accuracy was compared using Harrell's concordance coefficient (C). RESULTS: Over 64,888 patient-years of followup, there were 1317 deaths. Poorer baseline health status was associated with greater mortality risk. Adjusting for age, sex, and baseline PCS and MCS, declines in PCS and HAQ were associated with higher risk of death. HAQ improvement was associated with reduced mortality risk from 6 months through 3 years; a similar relationship was not observed for PCS or MCS improvement. Controlling for baseline values, change in PCS or HAQ did not improve prediction accuracy. CONCLUSION: The HAQ and the SF-36 PCS are similarly and strongly associated with mortality risk in patients with RA. Change in these measures over time does not appear to add to predictive accuracy over baseline levels.
21655937 Can bone quality be predicted accurately by Singh index in patients with rheumatoid arthri 2012 Jan The aim of this study was to evaluate Singh index as a simple and inexpensive means of estimation of bone quality in patients with rheumatoid arthritis. Singh index evaluation was made on digital pelvis radiographs in 50 consecutive patients by three observers. Bone mineral density T scores of the spine and left proximal femur were assessed using dual energy X-ray absorptiometry. Singh index was correlated with densitometry measurements after grouping the patients as normal, osteopenia and osteoporosis. Intra- and interobserver agreements were evaluated by kappa correlations. Sensitivity, specificity, positive and negative predictive values and likelihood ratio's of Singh index were calculated. Both intra- and interobserver agreements were 0.71 (range, 0.69 to 0.72) on average. Singh index proved highly sensitive for the diagnosis of osteopenia at the proximal femur (91%) and spine (90%), whereas the specificity of Singh index for identifying of osteoporosis at the femoral neck (93%) and spine (91%) was higher than sensitivity. Predictive values for osteoporosis at the proximal femur and spine were acceptable and positive likelihood ratios of Singh index for osteopenia and osteoporosis at the proximal femur were 2.4 and 10.1, respectively. Singh index can identify osteoporosis with a high specificity in patients with rheumatoid arthritis. However, the patients who are graded as osteopenia by the Singh index should undergo further evaluation with dual energy X-ray absorptiometry.
23092582 The interaction between CXCL10 and cytokines in chronic inflammatory arthritis. 2013 Mar There are several chemokines and their receptors involved in the pathogenesis of chronic inflammatory arthritis. Of those, CXCL10 and its receptor, CXCR3, are increased in many kinds of chronic inflammatory arthritis, especially in rheumatoid arthritis (RA). CXCL10 and CXCR3 play important roles in leukocyte homing to inflamed tissues and in the perpetuation of inflammation, and therefore, tissue damage. In addition to its chemotactic effect, CXCL10 may have pleiotropic functions. Our recent studies show that the crosstalk between CXCL10 and receptor activator of NF-κB ligand (RANKL) in inflamed synovial tissue may induce and perpetuate bone destruction in RA. The interaction between CXCL10 and tumor necrosis factor-α (TNF-α) can also contribute to sustained inflammation in RA. One human trial with anti-CXCL10 monoclonal antibody showed therapeutic potential of blocking CXCL10 in RA treatment. Understanding the novel interaction between this chemokine and other chemokines or cytokines may add possible therapeutic applications in inflammatory arthritis.
23017640 The Bengali Short Form-36 was acceptable, reliable, and valid in patients with rheumatoid 2012 Nov OBJECTIVE: To develop a culturally adapted Bengali version of the Short Form-36 (SF-36) Health Survey and to test its acceptability, reliability, and validity in patients with rheumatoid arthritis (RA). STUDY DESIGN AND SETTING: The US English SF-36 was translated into Bengali after established cross-cultural adaptation procedures. The questionnaire was interviewer administered to 125 consecutive outpatients with RA and readministered after 2 weeks to 40 randomly selected patients. RESULTS: Most participants (86.4%) did not have any problem in understanding the Bengali SF-36 and 98.4% of the questionnaires were fully completed. Only the role-physical and role-emotional scales showed substantial floor and ceiling effects. Principal component analysis confirmed that the hypothesized two-factor structure and tests of scaling assumptions were 100% successful for all eight scales expect physical functioning (98.8%) and general health (77.5%). Cronbach's α was higher than 0.78 and the test-retest reliability was high (r>0.82) for all scales. Correlations with other disease activity parameters were generally as expected and summary scores were able to discriminate between relevant subgroups. CONCLUSION: The interviewer-administered Bengali SF-36 appears to be an acceptable, reliable, and valid instrument for measuring health-related quality of life in Bangladeshi patients with RA. The questionnaire should be further evaluated in people from the general population and in patients with different medical conditions.
21461854 Serum adenosine deaminase may predict disease activity in rheumatoid arthritis. 2012 Jul To determine the relationship between serum adenosine deaminase (ADA) and disease activity, and to develop a new disease activity index based on serum ADA in rheumatoid arthritis (RA). Seventy RA patients were included. Disease activity based on Disease Activity Score 28-ESR (DAS28-ESR) and Disease Activity Score 28-CRP (DAS28-CRP) and serum ADA were measured. There were correlations when serum ADA compared with DAS28-ESR and DAS28-CRP. (R (2) = 0.014, 0.175, respectively, P values < 0.00). New disease activity index was developed by replacing ADA with ESR and CRP in DAS28-ESR and DAS28-CRP. There were strong correlations when new model compared with DAS28-ESR and DAS28-CRP. (R (2) = 0.94 and 0.95, respectively, P values < 0.00) The best new model values corresponding to DAS28-ESR values of 2.6, 3.2, and 5.1 were 2.79, 3.4, and 4.82, respectively; and new model values corresponding to DAS28-CRP values of 2.3, 2.7, and 4.1 were 2.1, 2.9, and 4, respectively. There were agreements when the new model compared with DAS28-ESR and DAS28-CRP for determination of patients in different disease activity categories. (Kappa = 0.81 and 0.71, respectively, P values < 0.00). The new disease activity index that applies serum ADA may help in predicting disease activity in RA.
22422556 Ultrasonographic hand features in systemic sclerosis and correlates with clinical, biologi 2012 Aug OBJECTIVE: To investigate ultrasonographic (US) hand features in systemic sclerosis (SSc) patients and their relationship with clinical, biologic, and radiographic data. METHODS: Fifty-two consecutive SSc patients were included in a cross-sectional observational study together with 24 rheumatoid arthritis (RA) patients enrolled as controls. All patients underwent clinical examination, including tender and swollen joint counts, measurement of disability indices, and hand/wrist radiographs. US was performed on the hand and wrist joints and was aimed at the detection of synovitis, tenosynovitis, and calcinosis. RESULTS: Synovitis and tenosynovitis were more frequently detected with US in SSc patients (46% and 27%, respectively) than with clinical examination (15% and 6%, respectively; P < 0.01 for both comparisons). Fifty-seven percent of patients had inflammatory synovitis (mostly Doppler grade 1), and tenosynovitis was either inflammatory or fibrotic. Calcifications were observed using US and radiographs in 40% and 36% of SSc patients, respectively (P = 0.8). As compared to RA, US features specific to SSc were sclerosing tenosynovitis (P < 0.01) and soft tissue calcifications (P = 0.01). CONCLUSION: Our study confirms that articular involvement in SSc is underestimated by a single clinical examination. It is characterized by mild inflammatory changes and the specific findings include sclerotic US aspects together with calcinosis. Further prospective studies are warranted to evaluate the predictive value of these findings and determine whether they should be considered for adapting a therapeutic strategy.
23135318 Serum undercarboxylated osteocalcin level increases with 48 weeks of teriparatide treatmen 2012 Oct AIM: The serum undercarboxylated osteocalcin (ucOC) level, a biochemical bone marker of vitamin K insufficiency, is often affected by anti-osteoporosis drugs. There have been no reports regarding the relationship between ucOC and teriparatide. SUBJECTS AND METHODS: We conducted a prospective observational study of 26 female rheumatoid arthritis (RA) patients. The patients were divided into 3 groups: those who underwent a direct switch from anti-resorptive drugs to teriparatide (12 cases), those who started teriparatide without pre-treatment (5 cases), and the control patients (9 cases). The median age (interquartile range) of the patients in each group was 75 (67-77), 82 (78-84), and 69 (62-80) yr, respectively. All patients, except controls, received 48-week treatments of teriparatide. We analyzed the median 48-week changes from baseline of the serum ucOC levels with the Steel-Dwass method. RESULTS: The median change from baseline in the direct switch group was higher than that in other groups (p<0.05). CONCLUSIONS: The serum ucOC levels increased with treatment of teriparatide in elderly RA patients, especially when the patients received pre-treatment.
23181974 Utility of combined high-resolution bone SPECT and MRI for the identification of rheumatoi 2013 Feb OBJECTIVES: To evaluate the utility of sequentially acquired, post hoc fused, magnetic resonance imaging (MRI) and multi-pinhole single photon emission computed tomography (MPH-SPECT) with technetium-99m-labeled disphosphonates (Tc99m-DPD) for the identification of finger joints with later erosive progression in early rheumatoid arthritis (ERA) patients. METHODS: Ten consecutive ERA patients prospectively underwent MPH-SPECT and MRI of metacarpophalangeal (MCP) joints prior to and after 6 months methotrexate therapy. Tc99m-DPD uptake was measured at proximal and distal MCP sites using regional analysis. The course of joint pathologies was scored according to the Rheumatoid Arthritis MRI Score (RAMRIS) criteria. RESULTS: The frequency of increased Tc99m-DPD uptake, synovitis and bone marrow edemadecreased under MTX therapy; but the number of bone erosions increased. Joints with progressive and new erosions on follow-up had a higher baseline Tc99m-DPD uptake (2.64 ± 1.23 vs. 1.43 ± 0.91) (p=0.02). CONCLUSIONS: Joints with erosive progression are characterized by an early increased Tc99m-DPD uptake, even in absence of MRI bone pathologies. Tc99m-DPD MPH-SPECT might thus be of additional value to morphological MRI for the identification of RA patients with a high risk for erosive progression.
21499088 Rheumatoid arthritis: is it a coronary heart disease equivalent? 2011 Jul PURPOSE OF REVIEW: This review examines current evidence to address the question whether rheumatoid arthritis (RA) is a coronary heart disease equivalent, similar to type 2 diabetes mellitus (DM2). RECENT FINDINGS: Cross-sectional and longitudinal epidemiological studies show a two-fold higher risk of cardiovascular disease (CVD) in patients with RA, and the magnitude of this increased risk is comparable to the risk associated with DM2. However, the mechanisms responsible for this appear to be different in the two conditions, with RA-related CVD being attributed to 'high-grade' systemic inflammation as well as classical CVD risk factors. Several classical risk factors are affected by RA or its medications, and there are some paradoxical associations between obesity or lipid abnormalities and CVD death in RA. SUMMARY: Management of RA-related CVD is likely to require both aggressive control of inflammation and systematic screening and management of classical CVD risk factors. It remains unknown whether primary prevention strategies applied successfully in DM2 would be equally easy to implement and demonstrate similar benefits in people with RA.
21279990 An oral Syk kinase inhibitor in the treatment of rheumatoid arthritis: a three-month rando 2011 Feb OBJECTIVE: To assess the efficacy and safety of R788 (fostamatinib disodium), an inhibitor of spleen tyrosine kinase (Syk), in patients with active rheumatoid arthritis (RA) that did not respond to biologic therapies. METHODS: A total of 219 patients with active RA in whom treatment with biologic agents had failed were enrolled in a 3-month multicenter, randomized, double-blind, placebo-controlled trial of R788. The primary end point was the percentage of patients who met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at month 3. Secondary end points included changes in inflammation and damage, as assessed by magnetic resonance imaging (MRI), and changes in the Disease Activity Score. RESULTS: The ACR20 response in the R788 100 mg twice daily group was 38%, versus 37% in the placebo group, at month 3. No significant differences were achieved in the ACR20, ACR50, or ACR70 response levels at 3 months. There were differences between the groups from baseline to month 3 in the secondary end points C-reactive protein (CRP) level and synovitis score on MRI. There were baseline differences in steroid use, prior biologic use, and synovitis score on MRI between the R788 group and the placebo group that may have affected the outcomes. A high placebo response rate was seen in this trial, and exploratory analysis suggested that this may in part have been driven by patients who entered the trial with an elevated erythrocyte sedimentation rate but normal CRP level. CONCLUSION: Our findings indicate that there were no differences in the primary end point between the R788 and placebo groups. Differences were observed between the R788 and placebo groups in secondary end points, particularly in those patients who entered the study with an elevated CRP level.
22810364 Effects of anti-tumor necrosis factor α agents on bone. 2012 Sep PURPOSE OF REVIEW: Tumor necrosis factor (TNF) inhibitors are effective for achieving disease control in several inflammatory diseases. Although anti-TNF agents can inhibit bone loss in vitro, their role in the prevention of clinically relevant outcomes such as osteoporosis and fractures has not been clearly established. RECENT FINDINGS: There are many studies of the effects of TNF inhibitors on markers of bone turnover; however, few have measured bone mineral density (BMD) or fractures. Most of these studies have small sample sizes and a minority had a placebo control group. Overall these studies suggest that the antiresorptive effects of anti-TNF therapy are related to control of disease activity. SUMMARY: The antiresorptive effects of TNF inhibitors are likely related to their anti-inflammatory properties. Studies to date have not demonstrated any advantages of TNF inhibitors over traditional nonbiologic therapies in the prevention of bone loss and fractures.
22540853 Relationship between disease activity and serum levels of vitamin D and parathyroid hormon 2012 Apr OBJECTIVE: Measuring vitamin D and its regulating hormones in the serum might be an accurate method for assessment of rheumatoid arthritis (RA) activity. We tested the hypothesis that the serum levels of vitamin D and parathyroid hormone (PTH) are associated with the grade of disease activity in an unselected cohort of patients with RA. METHODS: A total of 158 patients who met the American College of Rheumatology criteria for RA were examined and categorized as the patients with the active RA (n = 87) and silent RA (n = 71). Blood samples were obtained after at least eight-hour overnight fasting and the levels of 25-OH-vitamin D and PTH were measured. RESULTS: The levels of the vitamin D in patients with active RA were significantly lower than in those with silent RA (49.38±38.21 versus 64.64±43.61 nmol/l; p = 0.022). The PTH serum level lower than the normal range (< 0.8 nmol/l) was statistically observed similar in the active RA group compared with another ones (10.3 % versus 4.2 %, p = 0.149). Serum levels of vitamin D and PTH were not influenced by patients' gender and age as well as the duration of disease. CONCLUSION: Serum level of vitamin D was inversely related to RA activity and this relationship might be independent of PTH secretion or activity.
21595177 [The meaning of biologic therapy in the treatment of rheumatoid arthritis with the focus o 2011 Apr Current aims of management of rheumatoid arthritis (RA) patients are remission of the disease, or at least, achievement of its low activity. Early diagnosis of RA is highly important, allowing immediate start of therapy with classic disease modifying anti-rheumatic drugs (DMARDs). However, that kind of therapy does not guarantee achievement of therapeutic goals in all patients. In case of failure, introduction of biological drugs is necessary Despite a significant progress noted in RA therapy since introduction of tumour necrosis factor alpha (TNF-alpha) inhibitors several years ago, also that scheme failed to be effective in all cases of RA. New biological drugs characterised by a different mechanism of action than TNF-alpha inhibitors: Tocilizumab, Rituximab and Abatacept, are hope for non-responders to previous therapies.
22514152 Effect of body mass index on mortality and clinical status in rheumatoid arthritis. 2012 Oct OBJECTIVE: To study the relative risk (RR) of all-cause and cause-specific mortality in rheumatoid arthritis (RA) associated with body mass index (BMI), and to quantify the clinical and outcome consequences of abnormal BMI. METHODS: We studied mortality in 24,535 patients over 12.3 years, dividing patients into 3 age groups, <50, 50-70, and >70 years and fit Cox regression models separately within each age stratum. We used BMI categories of <18.5 kg/m(2) (underweight), 18.5 to <25 kg/m(2) (normal weight, reference category), 25 to <30 kg/m(2) (overweight), and ≥30 kg/m(2) (obesity). RESULTS: BMI ≥30 kg/m(2) was seen in 63-68% and underweight in ~2%. Reduction in the RR (95% confidence interval [95% CI]) for all-cause (AC) and cardiovascular mortality was seen for overweight (AC 0.8 [95% CI 0.8, 0.9]) and obese groups (AC 0.8 [95% CI 0.7, 0.8]), with and without comorbidity adjustment. Underweight was associated with increased mortality risk (AC 1.9 [95% CI 1.7, 2.3]). By contrast, obesity produced profound changes in clinical variables. Compared with normal weight, the odds ratio in the obese group was 4.8 for diabetes mellitus, 3.4 for hypertension, 1.3 for myocardial infarction, 1.4 for joint replacement, and 1.9 for work disability. Total semiannual direct medical costs were $1,683 greater, annual household income $6,481 less, pain scores 1.1 units higher, Health Assessment Questionnaire 0.28 higher, and EuroQol utility 0.7 units lower in the obese. CONCLUSION: Overweight and obesity reduce the RR of all-cause and cardiovascular mortality across different age groups and durations of RA. By contrast, overweight and obesity are associated with substantial increased risks of comorbidity, total joint replacement, greater pain, medical costs, and decreased quality of life.
22794936 [Increased cardiovascular risk and premature atherosclerosis in rheumatoid arthritis]. 2012 Aug Patients with rheumatoid arthritis (RA) are at increased risk of mortality compared with the general population. Evidence suggests that this increased mortality can largely be attributed to increased cardiovascular (CV) death. In a prospective study, 34 patients with RA were compared with age- and sex-matched controls. RESULTS: We found a lower C-HDL, apolipoprotein A1 and B in patients with RA. However, CT/C-HDL and C-LDL/C-HDL were significantly higher than control patients. The intima-media thickness was significantly higher in patients with RA (0.759 mm vs 0.558 mm; P<0.001). CONCLUSION: Increased attention to cardiovascular risk in RA will be necessary to reduce the excess CV mortality and morbidity in RA patients. It appears that the excess risk that is observed in the RA population can be explained, in part, by promotion of CV disease through increased systemic inflammation associated with RA.
21388353 Expression of activating and inhibitory leukocyte immunoglobulin-like receptors in rheumat 2011 Apr Rheumatoid arthritis (RA) is a heterogeneous chronic inflammatory joint disease characterized by excessive activation of inflammatory cells of which the underlying mechanisms are not fully elucidated. Perturbed expression and function of immune regulatory molecules called leukocyte immunoglobulin-like receptors (LILRs) may contribute to uncontrolled inflammation. LILRs primarily expressed on the surface of leukocytes are emerging as critical regulators of the threshold and amplitude of leukocyte activation. Inhibitory LILRs (LILRBs) contain cytoplasmic tails with immunoreceptor tyrosine-based inhibitory motifs that provide negative signals. Activating LILRs (LILRAs) have short cytoplasmic domains lacking signaling motifs but transmit activating signals by linking to immunoreceptor tyrosine-based activation motifs of the FcR γ-chain. Here we show that activating LILRA2, A5 and inhibitory LILRB2, B3 were abundantly expressed in synovial tissue of > 75% RA patients. Expression of LILRA2, A5, and B3 significantly correlated to disease activity. In contrast, LILRA1 and B4 were expressed in a subset of patients and no B1 or B5 expression was detected. LILRA2 and A5 were mainly expressed by synovial macrophages and endothelial cells but not lymphocytes, whereas B2 and B3 were expressed by macrophages and lymphocytes. Increase in the number of macrophages expressing activating LILRs and macrophages and lymphocytes expressing inhibitory LILRs suggest a crosstalk between these cells that may regulate the levels of cellular activation and disease severity, while differences in expression pattern may contribute to disease heterogeneity.