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.
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 (SLE-DAI) 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, antidouble-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.
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.
MIP-1alpha expression within inflamed joints appears to be regulated not only by inflammatory cytokines but also by the physical interaction of activated leucocytes and FLS, and plays a crucial role in the progression and maintenance of RA synovitis.
We evaluated the occurrence of cytomegalovirus (CMV) infection and the background characteristics in twenty-three hospitalized patients with inflammatory connective tissue diseases including systemic lupus erythematosus, polymyositis/dermatomyositis, rheumatoid vasculitis, microscopic polyangitis, and Takayasu's arteritis. Cytomegalovirus antigenemia was demonstrated in 10 of 23 evaluable patients. Five of ten patients with CMV antigenemia developed symptomatic CMV disease (all cases of fever, two cases of liver involvement, two cases of interstitial pneumonia, and one case of unknown organ involvement), whereas the remaining five patients were asymptomatic. Most of CMV antigenemia-positive patients had been administered intravenous steroid pulse, or in combination with immunosuppressive agents intravenously or orally because of refractory disease activity. Particularly, in patients who received intravenous methylprednisolone pulse in combination with additional intravenous cyclophosphamide pulse, the incidence of CMV antigenemia was markedly higher (four out of four). Four of ten CMV antigenemia-positive patients simultaneously showed detection of Pneumocystis jiroveci in induced sputum by PCR, increase in level of serum beta-D-glucan and the finding of geographical ground-glass opacities on chest computed tomography. These findings suggested that patients with connective tissue diseases under intensive immunosuppressive therapies (intravenous steroid pulse in combination with additional intravenous cyclophosphamide pulse in particular) are highly susceptible to CMV infection and disease, and that patients complicated by CMV antigenemia are susceptible to combined opportunistic infection such as Pneumocystis pneumonia.
We evaluated the occurrence of cytomegalovirus (CMV) infection and the background characteristics in twenty-three hospitalized patients with inflammatory connective tissue diseases including systemic lupus erythematosus, polymyositis/dermatomyositis, rheumatoid vasculitis, microscopic polyangitis, and Takayasu's arteritis. Cytomegalovirus antigenemia was demonstrated in 10 of 23 evaluable patients. Five of ten patients with CMV antigenemia developed symptomatic CMV disease (all cases of fever, two cases of liver involvement, two cases of interstitial pneumonia, and one case of unknown organ involvement), whereas the remaining five patients were asymptomatic. Most of CMV antigenemia-positive patients had been administered intravenous steroid pulse, or in combination with immunosuppressive agents intravenously or orally because of refractory disease activity. Particularly, in patients who received intravenous methylprednisolone pulse in combination with additional intravenous cyclophosphamide pulse, the incidence of CMV antigenemia was markedly higher (four out of four). Four of ten CMV antigenemia-positive patients simultaneously showed detection of Pneumocystis jiroveci in induced sputum by PCR, increase in level of serum beta-D-glucan and the finding of geographical ground-glass opacities on chest computed tomography. These findings suggested that patients with connective tissue diseases under intensive immunosuppressive therapies (intravenous steroid pulse in combination with additional intravenous cyclophosphamide pulse in particular) are highly susceptible to CMV infection and disease, and that patients complicated by CMV antigenemia are susceptible to combined opportunistic infection such as Pneumocystis pneumonia.
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.
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