Relationship Between the Lipidome Profile and Disease Activity in Patients with Rheumatoid Arthritis.

Lipid mediators have been suggested to play important roles in the pathogenesis of rheumatoid arthritis (RA). Lipidomics has recently allowed for the comprehensive analysis of lipids and has revealed the potential of lipids as biomarkers for the early diagnosis of RA and prediction of therapeutic responses. However, the relationship between disease activity and the lipid profile in RA remains unclear. In the present study, we performed a plasma lipidomic analysis of 278 patients with RA during treatment and examined relationships with disease activity using the Disease Activity Score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR). In all patients, five lipids positively correlated and seven lipids negatively correlated with DAS28-ESR. Stearic acid [FA(18:0)] (r = -0.45) and palmitic acid [FA(16:0)] (r = -0.38) showed strong negative correlations. After adjustments for age, body mass index (BMI), and medications, stearic acid, palmitic acid, bilirubin, and lysophosphatidylcholines negatively correlated with disease activity. Stearic acid inhibited osteoclast differentiation from peripheral blood monocytes in in vitro experiments, suggesting its contribution to RA disease activity by affecting bone metabolism. These results indicate that the lipid profile correlates with the disease activity of RA and also that some lipids may be involved in the pathogenesis of RA.

A case of subarachnoid and intracerebral hemorrhages complicated by trichosporonosis.

Background: Trichosporonosis has an extremely poor prognosis. In this report, we describe a case of subarachnoid hemorrhage and intracerebral hemorrhage due to a fungal aneurysm caused by Trichosporon. Case Description: A 71-year-old woman who experienced subcortical hemorrhage developed a subarachnoid hemorrhage. Endovascular parent artery occlusion was performed for a fungal aneurysm in the left posterior cerebral artery caused by Trichosporon. After surgery, voriconazole and liposomal amphotericin B were administered. The patient died of massive left putamen hemorrhage. Conclusion: Effective treatment for intracranial hemorrhage due to trichosporonosis has not yet been established and an accumulation of cases is required.

Efficacy of mycophenolate mofetil in Japanese patients with systemic lupus erythematosus.

OBJECTIVES: To assess the renal and non-renal efficacy of mycophenolate mofetil (MMF) in Japanese patients with systemic lupus erythematosus (SLE). METHODS: We conducted a retrospective study to assess the renal and non-renal efficacies of MMF in Japanese patients with systemic lupus erythematosus (SLE). We analyzed 14 patients with lupus nephritis (LN) who were given MMF, and 13 patients who received monthly intravenous cyclophosphamide (IVCY) as induction therapy, and a further 19 patients without LN who were treated with MMF, and 13 patients who took tacrolimus (TAC) to reduce glucocorticoid dosages. We assessed the therapeutic effects of each therapeutic regime on renal and non-renal disease manifestations over a six-month period after treatment initiation. RESULTS: Median urine protein to creatinine ratios in the MMF and IVCY groups significantly decreased from 2.2 to 0.7 g/gCr and from 3.3 to 0.5 g/gCr, respectively. Significant improvements in serum immunological variables (serum complements C3 and C4 and the anti-double stranded DNA antibody) and reductions in the SLE disease activity index (SLEDAI) and daily prednisolone dosages were observed in each group with LN. MMF and TAC significantly improved SLEDAI and serum immunological variables and reduced daily prednisolone dosages in patients without LN. CONCLUSION: The present results demonstrated that MMF might be an effective treatment for renal and non-renal manifestations in Japanese patients with SLE and has potential as a good therapeutic alternative and steroid-sparing agent.

The growth factor midkine may play a pathophysiological role in rheumatoid arthritis.

OBJECTIVES: Midkine (MK) is involved in cell proliferation, differentiation, migration, and survival. In this study, we measured serum MK levels in rheumatoid arthritis (RA) and investigated the correlation of serum MK with RA disease activity. Expression and effect of MK in RA synovial tissue were also examined. METHODS: Serum MK and production of inflammatory mediators by rheumatoid synovial fibroblasts (RSFs) were measured by enzyme-linked immunosorbent assay. MK expression in synovial tissue was examined by immunohistochemistry. MK receptor expression was analyzed by RT-PCR and Western blotting. RESULTS: RA patients had a significantly higher serum MK level than healthy controls. In RA patients, the MK level was correlated with DAS28-ESR, disability index of the Health Assessment Questionnaire, and rheumatoid factor level. The serum MK level tended to be decreased by anti-TNF therapy. MK was expressed by synovial lining cells in RA synovial tissues and it enhanced the production of IL-6, IL-8, and CCL2 by RSFs. RSFs expressed LDL receptor-related protein 1, candidate receptor for MK. CONCLUSIONS: The serum MK level could be a marker of disease activity in RA and an indicator of a poor prognosis. MK may have a role in the pathogenesis of RA via induction of inflammatory mediators.

Efficacy of Vitamin K2 for Glucocorticoid-induced Osteoporosis in Patients with Systemic Autoimmune Diseases.

Objective Vitamin K2 (menatetrenone) is an effective treatment for patients with postmenopausal osteoporosis. We herein performed a subanalysis of patients with systemic autoimmune diseases undergoing glucocorticoid therapy in our previous prospective study. Methods Sixty patients were categorized into a group with vitamin K2 treatment (n=20, Group A) and a group without vitamin K2 treatment (n=40, Group B). All patients were treated with bisphosphonates. Results Serum levels of osteocalcin and undercarboxylated osteocalcin decreased significantly after the start of glucocorticoid therapy in both groups, while the serum osteocalcin level was significantly higher in Group A than Group B during the third (p=0.0250) and fourth weeks (p=0.0155). The serum level of the N-terminal peptide of type I procollagen, a bone formation marker, decreased during glucocorticoid therapy, but was significantly higher in Group A than Group B during the fourth week (p=0.0400). The bone mineral density and fracture rate showed no significant differences between the two groups. Conclusion Although vitamin K2 improves bone turnover markers in patients with osteoporosis on glucocorticoid therapy, it has no significant effect on the bone mineral density and fracture rate after 1.5 years of treatment.

Systemic lupus erythematosus complicated by recurrent pneumothorax: Case report and literature review.

Pneumothorax is a rare pleuropulmonary manifestation of systemic lupus erythematosus. We encountered a 37-year-old Japanese woman who had systemic lupus erythematosus complicated by recurrent pneumothorax during treatment for recurrent serositis with glucocorticoid therapy. She was admitted for the third episode of lupus peritonitis in December 2005. Intravenous cyclophoshamide and increased dose of oral prednisolone were administered. In early January 2006, hemoptysis was observed and bronchofiberscopy revealed hemorrhage from the left lower lobe. After intravenous methylprednisolone pulse therapy and oral cyclosporine therapy were added, pleurisy and pulmonary hemorrhage improved. On February 22nd, she suddenly developed pneumothorax on the right side, followed by pneumothorax on the left side after 2 days. This pneumothorax on the left side did not improve despite chest tube drainage for over one month. She underwent thoracoscopic partial lobectomy of lower lobe of the left lung, and her symptoms improved. Review of the literature identified 10 case reports of systemic lupus erythematosus complicated by pneumothorax. All of the patients including our case had underlying pulmonary lesions, and 9/11 patients had pleurisy. Besides 10/11 patients received glucocorticoid therapy before the occurrence of pneumothorax. Tissue fragility caused by these factors might contribute to the complication of pneumothorax in patients with systemic lupus erythematosus.

Exacerbation of adult-onset Still's disease, possibly related to elevation of serum tumor necrosis factor-alpha after etanercept administration.

Adult-onset Still's disease (AOSD) is a systemic inflammatory disease of unknown etiology. A 44-year-old male patient presented with AOSD complicated by macrophage activation syndrome after etanercept therapy. His serum tumor necrosis factor-α (TNF-α) level was increased dramatically after etanercept therapy. The clinical course of this case suggests that the increased TNF-α level by etanercept administration might cause macrophage activation syndrome in this case.

Pharmacokinetic study and Fcgamma receptor gene analysis in two patients with rheumatoid arthritis controlled by low-dose infliximab.

The main aim of this study is to investigate the pharmacokinetics of infliximab and Fcgamma receptor (FcgammaR) polymorphism in two patients with rheumatoid arthritis (RA) who were well controlled by low-dose infliximab. A 57-year-old woman (Patient 1) and a 67-year-old woman (Patient 2) had active RA despite methotrexate and prednisolone treatments. They improved after the addition of infliximab (3 mg/kg), but developed pneumonia and sepsis, respectively. Although the infliximab doses were reduced to 1.5 mg/kg and 1 mg/kg, respectively, clinical improvements were maintained. Blood samples were obtained at 1 h after infliximab administration and at eight weeks (just before the next dose). The elimination half-life was determined by the serum concentration of infliximab. We also analyzed the polymorphisms of FcgammaRIIA, FcgammaRIIIA, and FcgammaRIIIB for the genomic DNA samples from the two patients and three controls. Amplification of the FcgammaR-genomic regions in allotype-specific polymerase chain reactions was used to distinguish the genotypes. Decresed clearance of infliximab was proven by a pharmacokinetic study of these patients under low-dose infliximab therapy. 131H/H (FcgammaRIIA) and 176F/F (FcgammaRIIIA) were detected in both patients. NA1/NA2 and NA2/NA2 (FcgammaRIIIB) were detected in Patients 1 and 2, respectively. These patients were well controlled over the long term by low-dose infliximab. The mechanism of the reduced clearance of infliximab might possibly be explained in part by the FcgammaR polymorphisms.