Adherence to methotrexate and associated factors considering social desirability in patients with rheumatoid arthritis: a multicenter cross-sectional study.

BACKGROUND: Assessing medication adherence in rheumatoid arthritis (RA) is clinically significant as low adherence is associated with high disease activity. Self-reported medication adherence surveys have been shown to have problems with overestimation of adherence due to social desirability bias. However, no MTX adherence studies adjusted for social desirability have been conducted to date. This study aimed to evaluate adherence to MTX and perform an investigatory search for factors associated with MTX adherence including social desirability. METHODS: This cross-sectional multicenter study was conducted among adult RA patients consuming oral MTX for ≥ 3 months. We examined the distribution of MTX adherence, according to the eight-item Morisky Medication Adherence Scale (MMAS-8). Social desirability was using the Social Desirability Scale (SDS). Furthermore, an exploratory factor analysis involving social desirability was examined to identify factors associated with MTX adherence using linear regression analysis. To deal with missing values, we used multiple imputations with chained equations methods. RESULTS: A total of 165 RA patients were enrolled. The median age was 64 years, and 86.1% were women. Based on the MMAS-8, low, medium, and high adherences were noted in 12.1%, 60.0%, and 27.9% of participants, respectively. High social desirability (coefficient, 0.14; 95% confidence interval [CI], 0.05-0.23; p < 0.05) and high age (coefficient per 10 years, 0.16; 95% CI, 0.01-0.03; p < 0.05) were associated with high MTX adherence, whereas full-time work was negatively associated with high MTX adherence (coefficient, -0.50; 95% CI, -0.95--0.05; p < 0.05). CONCLUSIONS: A large proportion of patients with RA do not take MTX as prescribed. High social desirability, high educational level, and non-full-time work may be associated with high MTX adherence. Physicians should confirm MTX adherence before switching or adding disease-modifying anti-rheumatic drugs in cases of uncontrolled disease activity.

[The Abdominal Ultrasonographic Appearance of Acute Phlegmonous Gastritis].

Phlegmonous gastritis (PG) is a nonspecific suppurative inflammation disease arising from the submucosal layer, and extending to the full thickness of the stomach. We herein report on a case of acute PG which was diagnosed with abdominal ultrasonography. A 64-year-old man presented at a hospital after having recently undergone pacemaker implantation for the treatment of complete atrioventricular block. He was admitted as an emergency due to a fever of 39 degrees C. He showed anorexia, epigastralgia, vomiting of coffee-ground emesis on the second hospital day, and abdominal ultrasonography (AUS) performed on the third hospital day showed the disappearance of the normal laminated structure and hypoechoic thickening of the stomach walls. Upper gastrointestinal endoscopy revealed significant hyperplasia of the stomach walls, an erythrogenic mucosa, and poor extension. On the fourth hospital day, computed tomography revealed concentric thickening of the stomach walls. Streptococcus pyogenes was cultured from his blood sample. Based on those findings, the patient was diagnosed as having acute phlegmonous gastritis. His clinical symptoms improved and the abnormal ultrasonographic examination findings thereafter returned to normal following the administration of antibiotics. PG should therefore be included in the differential diagnosis when encountering patients with acute abdomen. We experienced a rare case of acute phlegmonous gastritis and AUS was useful for making an early diagnosis.

A Delayed Cerebral Vasospasm with Infarction Is Secondary to Listeria monocytogenes Meningitis: MRI and MRA Are Diagnostically Useful.

Among patients with bacterial meningitis, a cerebral vasospasm typically occurs during the acute phase. We experienced a case of delayed cerebral vasospasm with infarction that was secondary to Listeria monocytogenes meningitis. An 82-year-old woman with Listeria monocytogenes meningitis, whose symptoms had been improving after the initiation of antibacterial therapy, fell into a coma on day 15 and developed generalized seizure. Magnetic resonance imaging (MRI) and MR angiography (MRA) indicated a cerebral vasospasm with multiple infarctions. The risk of vascular complications following acute bacterial meningitis requires close follow-up to identify neurological changes and a low threshold for vascular evaluation. In such cases, MRI and MRA have diagnostic utility.

Therapeutic Efficacy of Leukocytapheresis in a Pregnant Woman with Refractory Adult-onset Still's Disease.

This is the first report of the efficacy of leukocytapheresis (LCAP) in a patient with refractory adult onset Still's disease (AOSD) during pregnancy. A 32-year-old Chinese pregnant woman with AOSD who had been treated with prednisolone failed to achieve disease stabilization. The patient's disease was successfully controlled with the initiation of LCAP. Subsequently, she gave birth via Caesarean section to a 1,878 g baby boy at 34 weeks of gestation while maintaining remission. We conclude that LCAP is an alternative treatment in pregnant patients with refractory AOSD, particularly in those concerned about potential teratogenic and other adverse effects.

Depression is improved when low-dose tacrolimus is given to rheumatoid arthritis patients showing an inadequate response to biologic agents.

PURPOSE: Depression in rheumatoid arthritis (RA) patients is more severe than in healthy people. Herein, we report improved depression in RA patients using biologic agents. We examined whether depression was improved by tacrolimus combination therapy when biologic agents were ineffective. METHOD: The study included 13 RA patients who used biologic agents. The following methods were used before the initiation of tacrolimus combination therapy and at 14 and 30 weeks after treatment initiation: the Zung self-rating depression scale (SDS) to evaluate depression state, disease activity score 28/erythrocyte sedimentation rate (DAS28), tender joint counts, swollen joint counts, a patient global assessment to evaluate RA disease activity, and the modified health assessment questionnaire (mHAQ) to evaluate quality of life. RESULTS: The SDS scores before the initiation of tacrolimus combination therapy and at 14 and 30 weeks after treatment initiation were 45.2 ± 10.6, 44.8 ± 12.8, and 41.6 ± 11.2 (p = 0.047), respectively, indicating significant improvement. The DAS28 was 5.0 ± 1.3 prior to treatment, 3.8 ± 1.3 at 14 weeks, and 3.5 ± 0.9 at 30 weeks, demonstrating significant improvement at both 14 and 30 weeks (p < 0.001). The mHAQ score changed from 0.60 ± 0.45 at baseline to 0.54 ± 0.52 and 0.38 ± 0.43 at 14 and 30 weeks, respectively. The mHAQ score was significantly lower at 30 weeks when compared to baseline (p = 0.013). CONCLUSION: Tacrolimus combination therapy does not directly improve depression in RA patients, but it is possible that the observed improvement in depression accompanies the improvement in the secondary failure of RA.

Elevated serum levels of macrophage migration inhibitory factor and their significant correlation with rheumatoid vasculitis disease activity.

Macrophage migration inhibitory factor (MIF) is recognized to be an important mediator in several inflammatory disorders, including rheumatoid arthritis (RA) and vasculitis. To evaluate the role of MIF in rheumatoid vasculitis (RV), we determined serum levels of MIF by enzyme-linked immunosorbent assay in RA patients with and without vasculitis and assessed their relationship to disease activity. Serum was obtained from 95 RA patients during active disease states [49 without vasculitis, 35 with extra-articular manifestations without histologically proven vasculitis, and 11 with histologically proven vasculitis] and from 22 healthy individuals. Vasculitis disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). MIF levels were significantly higher in RA patients than in controls. Moreover, MIF levels were significantly higher in RA patients with vasculitis than in those without vasculitic complications. In all RA patients, a statistically significant positive correlation was observed between serum MIF levels and each of the following: serum levels of C-reactive protein, rheumatoid factor, and thrombomodulin; and the erythrocyte sedimentation rate. In the RV group, the elevation of MIF levels correlated with the BVAS. Our findings suggest that MIF may serve as an additional serologic inflammatory marker of disease activity in RV, and it may be implicated in the pathogenesis of RV.

Involvement of CX3CL1/CX3CR1 axis in etanercept therapy for patients with active rheumatoid arthritis.

OBJECTIVE: To examine the relationship between serum chemokine levels and patient responsiveness in rheumatoid arthritis (RA) patients to etanercept (ETN) and the influence of ETN administration on serum chemokine levels. METHODS: Serum levels of the chemokines CX3CL1, CXCL8, CXCL10, and CCL3 were quantified prior to (at baseline) and after 14 weeks of treatment with ETN in 20 patients using enzyme-linked immunosorbent assay. Disease status was assessed using the Disease Activity Score (DAS28). The response to ETN was classified according to the European League Against Rheumatism (EULAR) response criteria. RESULTS: By 14 weeks, ETN produced a significant overall reduction in DAS28 among the 20 patients with RA; eight patients achieved a good response, and 10 patients achieved a moderate response based on EULAR response criteria. A significant reduction in CX3CL1 was observed in the responsive group, although ETN treatment had no significant effect on the serum levels of the other three chemokines. In addition, the messenger ribonucleic acid expression of CX3CR1 in peripheral blood mononuclear cells and the cell-surface expression of CX3CR1 protein in peripheral blood CD8+CD3+ T cells were both decreased after ETN treatment. CONCLUSIONS: Our results suggest that the CX3CL1 and CX3CR1 in patients with active RA may be sensitive to antitumor necrosis factor-α therapy and confirm that CX3CL1/CX3CR1 axis plays a crucial role in the pathogenesis of RA.

Dermatomyositis complicated with hemorrhagic shock of the iliopsoas muscle on both sides and the thigh muscle.

A 65-year-old Japanese woman, diagnosed with dermatomyositis with myopathy and characteristic skin lesion, was intravenously administered methylprednisolone 500 mg per day for 3 days, followed by prednisolone 60 mg po per day. Four days later, she went into shock. Computed tomography of the abdomen showed hematoma in the iliopsoas muscle on both sides and a thigh muscle. Intravenously administered heparin was stopped, and 4 U of packed cells and 4 U of fresh frozen plasma were transfused. The patient subsequently developed pulmonary edema requiring assisted ventilation, and made a successful recovery, returning home after a short period of intensive rehabilitation.

Effects of low-dose mizoribine pulse therapy in combination with methotrexate in rheumatoid arthritis patients with an insufficient response to methotrexate.

The aim was to determine the efficacy of low-dose intermittent pulse administration of mizoribine (MZR), a purine synthesis inhibitor, in combination with methotrexate (MTX) to control the symptoms of rheumatoid arthritis (RA) in patients with an insufficient clinical response to MTX alone. Twenty-seven patients with active RA, despite treatment with MTX, were enrolled and given MZR in combination with MTX and continued for 24 weeks. The primary endpoint was assessment of clinical improvements using the European League against Rheumatism (EULAR) criteria. Administering MZR to RA patients with an insufficient response to MTX produced significant improvements in the Disease Activity Score 28 (DAS28) after 8-24 weeks. In addition, after 24 weeks, 60.0% and 8.0% of patients had achieved moderate and good responses, respectively, and there were significant reductions in Modified Health Assessment Questionnaire and serum matrix metalloproteinase-3 levels. The present preliminary study suggests that low-dose MZR in combination with MTX is well tolerated and provides both clinical and economic benefits.

Correlation of CX3CL1 and CX3CR1 levels with response to infliximab therapy in patients with rheumatoid arthritis.

OBJECTIVE: To examine the relation between serum chemokine levels and patient responsiveness to infliximab, and the influence of infliximab administration on serum chemokine levels. METHODS: Serum levels of the chemokines CX3CL1, CXCL8, CCL3, and CXCL10 were quantified prior to (at baseline) and after 30 weeks of treatment with infliximab in 20 patients using enzyme-linked immunosorbent assays. Disease status was assessed using the Disease Activity Score (DAS28). The response to infliximab was classified according to the European League Against Rheumatism (EULAR) response criteria. RESULTS: By 30 weeks, infliximab produced a significant overall reduction in DAS28 among the 20 patients with RA, although only 12 achieved a good to moderate response based on EULAR response criteria. A significant reduction in CX3CL1 was seen in the responsive group, although infliximab treatment had no significant effect on the serum levels of the other 3 chemokines. Comparison of patients with lower (<2000 pg/ml) and higher (>or=2000 pg/ml) basal CX3CL1 levels revealed that DAS28, erythrocyte sedimentation rate, C-reactive protein, and CX3CL1 levels were all significantly diminished by infliximab in RA patients with lower basal CX3CL1 levels, but not in those with higher basal levels. In addition, cell-surface expression of CX3CR1 protein in peripheral blood CD8+CD3+ T cells and mRNA expression of CX3CR1 in lymphocytes were both significantly downregulated after infliximab treatment in the responsive group. CONCLUSION: Our results suggest that the CX3CL1-CX3CR1 system in patients with active RA may be sensitive to anti-tumor necrosis factor-alpha therapy, and confirm that CX3CL1 plays a crucial role in the pathogenesis of RA.

Increased serum levels of macrophage migration inhibitory factor (MIF) in patients with microscopic polyangiitis.

OBJECTIVE: To test the hypothesis that macrophage migration inhibitory factor (MIF) is involved in the disease activity of systemic vasculitis. METHODS: Patients with systemic vasculitis were divided into three groups based on the size of the affected vessels. Microscopic polyangiitis (MPA) was considered as small vessel vasculitis (SVV), polyarteritis nodosa as medium-sized vessel vasculitis (MVV), and giant cell arteritis and Takayasu arteritis as large vessel vasculitis (LVV). Sera from patients with systemic vasculitis and healthy individuals were collected, and MIF levels were measured using an enzyme-linked immunosorbent assay. Disease activity of vasculitis was assessed using the Birmingham Vasculitis Activity Score (BVAS). RESULTS: Serum MIF levels were significantly higher in the vasculitis patients than in healthy individuals. Among the vasculitis patients, MIF levels were significantly higher in patients in the SVV group (median; 4161.7 pg/ml) than in the other groups (MVV; 1443.2 pg/ml and LVV; 1576.7 pg/ml). In patients with MPA, a positive correlation was observed between serum MIF levels and CRP levels and disease activity (BVAS). Notably, serum MIF levels were significantly diminished after clinical improvement. CONCLUSIONS: Our findings suggest that MIF may have an important role in small vessel vasculopathy and serve as a useful serologic marker of MPA disease activity.

Clinical features of hemophagocytic syndrome in patients with dermatomyositis.

OBJECTIVE: To investigate the clinical features of patients with dermatomyositis (DM) complicated by hemophagocytic syndrome (HPS). METHODS: Twenty-four patients diagnosed with DM and treated at our hospital between January 2002 and April 2007 were enrolled for study. Serum levels of various parameters including cytokines were determined during the active disease states. RESULTS: Levels of serum ferritin, creatine kinase, and immune complexes were all significantly higher in all patients with HPS than in those without HPS. Levels of soluble interleukin-2 receptor, macrophage colony stimulating factor, and the chemokine CX3CL1 were significantly elevated in DM patients with HPS. CONCLUSION: Our findings suggest that mechanisms related to both circulating immune complexes and circulating cytokines are involved in the pathogenesis of HPS complicating DM.

Effect of the H2 receptor antagonist nizatidine on xerostomia in patients with primary Sjögren's syndrome.

In Sjögren's syndrome (SS), oral dryness (xerostomia) is frequently the most bothersome symptom. An H2 histamine receptor antagonist is often administered to SS patients to treat associated superficial gastritis. The aim of the present study was to assess the ability of nizatidine, an H2 receptor antagonist, to also relieve xerostomia in patients with primary SS. Twenty-seven patients with primary SS were randomly assigned to receive nizatidine (n=14, 300 mg a day) or another H2 blocker, famotidine (n=13, 40 mg a day; control), were followed for eight weeks, and were asked for both subjective and objective assessments of oral dryness using a visual analog scale (VAS; 1-100 mm) and the Saxon's test, respectively. Patients receiving oral nizatidine, but not famotidine, obtained significant objective relief from their xerostomia (Saxon's test; baseline, 0.57 g/2 min; after eight weeks, 0.90 g/2 min, P<0.05). VAS scores indicated that nizatidine also provides mild improvement (20% improvement over baseline) of xerostomia-related clinical conditions, including mouth dryness and difficulty in chewing, tasting and swallowing food. Both drugs were generally well tolerated, without adverse effects. The present preliminary study suggests that nizatidine may represent a new option for the treatment of xerostomia in SS.

Tacrolimus-induced lung injury in a rheumatoid arthritis patient with interstitial pneumonitis.

A 74-year-old woman was experiencing rheumatoid arthritis complicated with interstitial pneumonitis (IP), and tacrolimus treatment was started. She presented with dyspnea. Chest X-ray and computed tomography (CT) showed ground-glass opacity and IP. Although tacrolimus was stopped, she died of respiratory failure. At autopsy, both the upper and lower lung fields showed usual IP and the organizing stage of diffuse alveolar damage. The former is common, but the latter is uncommon, suggesting tacrolimus may cause severe alveolar damage.

Synergistic induction of CX3CL1 by TNF alpha and IFN gamma in osteoblasts from rheumatoid arthritis: involvement of NF-kappa B and STAT-1 signaling pathways.

To explore the regulation of CX3CL1 in inflammatory bone diseases, CX3CL1 expression by osteoblasts (OB) was examined. Human OB isolated from rheumatoid arthritis (RA) patients, osteoarthritis patients, and normal individuals were incubated in the presence of cytokines. Soluble CX3CL1 levels were determined with an enzyme-linked immunosorbent assay. Expression of CX3CL1 mRNA was examined using quantitative real-time polymerase chain reaction. Although tumor necrosis factor (TNF)-α or interferon (IFN)-γ alone RA OB induced negligible CX3CL1 secretion, the combination of TNF-α and IFN-γ induced dramatic increases in both soluble CX3CL1 protein and mRNA transcripts. This synergistic effect was more pronounced in OB from RA than in OB from either osteoarthritis or normal individuals. The expression of CX3CL1 was markedly reduced by specific inhibitors of the nuclear factor-κB (NF-κB) or STAT-1 transcription factor. These findings suggest that osteoblasts are an important cellular source of CX3CL1 and may play roles in inflammatory bone/joint diseases.

Chemokines in systemic lupus erythematosus involving the central nervous system.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multi-organ damage and neuropsychiatric complications (NPSLE) associated with increased morbidity and mortality. The pathogenesis of NPSLE is not yet fully understood, but focal symptoms are thought to most likely result from vascular lesions, whereas diffuse manifestations are more likely related to autoantibody- or cytokine-mediated impairment of neuronal function. Recent progress also has provided evidence that levels of several cytokines/chemokines are upregulated in the central nervous systems of NPSLE patients during active disease and downregulated by treatment. In particular, chemokines appear to play significant roles in both inflammatory and immunological processes in the brain. For instance, we recently showed that levels of the soluble form of the chemokine CX3CL1 are elevated in the cerebrospinal fluid of patients with active NPSLE. In this review, we will discuss the involvement of chemokines in the pathogenesis of NPSLE and their significance as a useful laboratory parameter indicative of active neuropsychiatric disease.

Expression of angiopoietin-1 in osteoblasts and its inhibition by tumor necrosis factor-alpha and interferon-gamma.

Angiogenesis is a crucial component of bone remodeling under both normal and pathophysiological conditions. Among the various mediators that regulate the angiogenic process is the angiopoietin (Ang) family of growth factors. Ang-1 stabilizes new blood vessels by recruiting surrounding mesenchymal cells and promoting their differentiation into vascular smooth muscle cells, whereas Ang-2 is a natural antagonist of Ang-1 and can inhibit angiogenesis. The expression of Ang-1 and Ang-2 in human osteoblasts (hOBs) isolated from rheumatoid arthritis (RA) and osteoarthritis (OA) patients and from healthy individuals has been examined. After incubation in the presence or absence of tumor necrosis factor-alpha (TNF-alpha) and/or interferon-gamma (IFN-gamma), the culture supernatants were assayed for Ang using an enzyme-linked immunosorbent assay. In addition, expression of Ang protein and mRNA was examined using immunohistochemical techniques and quantitative real-time polymerase chain reaction, respectively. It was found that hOBs expressed Ang-1 but not Ang-2 protein, and cultured hOBs from RA and OA patients and from healthy individuals all spontaneously secreted significant amounts of Ang-1 in the absence of any stimulation. Although stimulation with TNF-alpha or IFN-gamma had little or no effect on Ang-1 secretion, costimulation with IFN-gamma plus TNF-alpha dose- and time-dependently diminished secretion of Ang-1 from hOBs. This inhibitory effect was mediated in part by nuclear factor-kappa B via upregulated expression of inducible nitric oxide synthase and enhanced synthesis of nitric oxide. Taken together, these findings suggest that OBs are an important cellular source of Ang-1 and may modulate bone remodeling through regulation of angiogenesis.

Increased serum levels of soluble fractalkine (CX3CL1) correlate with disease activity in rheumatoid vasculitis.

OBJECTIVE: To determine levels of soluble fractalkine (sFkn) in rheumatoid arthritis (RA) patients with and without rheumatoid vasculitis (RV), and to assess the relationship of sFkn levels to disease activity. METHODS: Serum was obtained from 98 RA patients (54 without vasculitis, 36 with extraarticular manifestations but without histologically proven vasculitis, and 8 with histologically proven vasculitis) and from 38 healthy individuals. Levels of sFkn were measured by enzyme-linked immunosorbent assay. Expression of Fkn and CX(3)CR1 was quantified by real-time polymerase chain reaction. Vasculitis disease activity was assessed using the Birmingham Vasculitis Activity Score and the Vasculitis Activity Index. RESULTS: Serum sFkn levels were significantly higher in patients with RA than in controls and were significantly higher in RA patients with RV than in those without vasculitic complications. Statistically significant correlations were observed between serum sFkn levels in RA patients and levels of C-reactive protein, rheumatoid factor, immune complex, and complement. In the RV group, sFkn levels also correlated with disease activity. Immunohistochemical analysis indicated that Fkn levels were associated mainly with endothelial cells in vasculitic arteries. In addition, expression of CX(3)CR1 messenger RNA was significantly greater in peripheral blood mononuclear cells from patients with active RV than in those from other RA patients or controls. Notably, serum sFkn levels were significantly diminished following successful treatment and clinical improvement. CONCLUSION: These findings suggest that Fkn and CX(3)CR1 play crucial roles in the pathogenesis of RV and that sFkn may serve as a serologic inflammatory marker of disease activity in RA patients with vasculitis.

Neutrophil-derived cytokines: potential therapeutic targets in inflammation.

Polymorphonuclear neutrophils (PMNs) are usually thought of as the leukocyte population involved in acute inflammatory responses, acting as a first line of defense against invading microorganisms. These terminally differentiated cells are generally not thought of as an important source of de novo synthesis of polypeptide mediators. Recent progress has shown, however, that PMNs are able to synthesize cytokines in response to a variety of inflammatory stimuli and during certain pathological conditions. The expression profiles of PMN-derived cytokines are similar with those of monocytes/macrophages, major professional phagocytes. Like monocytes, PMNs are able to secrete proinflammatory cytokines [e.g., tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta], both CC and CXC chemokines [e.g., IL-8, interferon-inducible protein 10 (IP-10) and macrophage inflammatory protein (MIP)-1alpha], and angiogenic factors [e.g., vascular endothelial growth factor (VEGF)]. The secretion of cytokines by activated PMNs is regulated by immunoregulatory cytokines such as interferon (IFN)-gamma, IL-4, IL-10 and IL-13. In addition to acute inflammatory responses, PMNs and PMN-derived cytokines appear to be involved in the pathogenesis of such chronic inflammatory disorders as rheumatoid arthritis, inflammatory bowel diseases and mycobacterial infections. Conceivably, these findings place PMNs at a pivotal position where they regulate and orchestrate not only acute inflammatory responses but also chronic inflammation and immune regulation. As such, inhibition of PMN-derived cytokines is viewed as a potentially useful strategy for therapeutic immunointervention.

Elevated levels of soluble fractalkine in active systemic lupus erythematosus: potential involvement in neuropsychiatric manifestations.

OBJECTIVE: To determine levels of the soluble form of the chemokine fractalkine (sFkn) and its receptor, CX(3)CR1, in patients with systemic lupus erythematosus (SLE) with neuropsychiatric involvement (NPSLE) and in SLE patients without neuropsychiatric involvement, and to assess their relationship with disease activity and organ damage. METHODS: Levels of sFkn in serum and cerebrospinal fluid (CSF) were measured by enzyme-linked immunosorbent assay. Expression of Fkn and CX(3)CR1 was quantified using real-time polymerase chain reaction. Surface expression of CX(3)CR1 on peripheral blood mononuclear cells (PBMCs) was determined by flow cytometry. Disease activity and organ damage were assessed using the SLE Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index, respectively. RESULTS: Serum sFkn levels were significantly higher in patients with SLE than in patients with rheumatoid arthritis (RA) or healthy controls. In addition, significant correlations between serum sFkn levels and the SLEDAI, the SLICC/ACR Damage Index, anti-double-stranded DNA and anti-Sm antibody titers, immune complex levels (C1q), and serum complement levels (CH50) were observed. Expression of CX(3)CR1 was significantly greater in PBMCs from patients with active SLE than in those from RA patients or healthy controls. Levels of sFkn were also significantly higher in CSF from untreated patients with newly diagnosed NPSLE than in SLE patients without neuropsychiatric involvement; treatment reduced both serum and CSF levels of sFkn in patients with SLE. CONCLUSION: Soluble Fkn and CX(3)CR1 may play key roles in the pathogenesis of SLE, including the neuropsychiatric involvement. Soluble Fkn is also a serologic marker of disease activity and organ damage in patients with SLE, and its measurement in CSF may be useful for the diagnosis of NPSLE and followup of patients with NPSLE.