Satoko Arai

Dokkyo Medical University, Totigi, Tochigi, Japan

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Publications (13)51.1 Total impact

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    ABSTRACT: Background Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an important hematopoietic growth factor, particularly for differentiation of alveolar macrophage, and immune modulator including inflammation. Neutralizing autoantibodies against GM-CSF antibodies cause pulmonary alveolar proteinosis (PAP). We have previously reported a SLE patient with anti-GM-CSF antibody (Ab) and PAP (Lupus 2013;22, 1060). However, it remains unknown whether there exist autoantibodies against GM-CSF in connective tissue disease (CTD) patients without PAP. Objectives To determine whether anti-GMF autoantibody is detected in sera from CTD patients. If so, to determine whether the antibody has neutralizing activity and to clarify the clinical features of patients with the antibody. Methods Subjects were 245 CTD patients (SLE; 63, DM/PM; 49, RA; 106, vasculitis; 27) and 34 healthy controls. A EIA system to detect anti-GM-CSF Abs was developed; GM-CSF was coated on the plate that was then blocked with BSA, diluted serum with PBS was added, and after washing the Ab was detected by anti-IgG Ab. To avoid non-specific binding, the optic density (OD) of the Ab was calculated as follows; OD (GM-CSF coated well) -OD (GM-CSF negative well). The neutralizing activity of the Ab was examined through inhibition of CD11b expression on neutrophils by GM-CSF; neutrophils were incubated in media with GM-CSF (5ng/ml) and serum from the subjects, and CD11b expression was examined using flowcytometry. Association of clinical features with the Ab was assessed by reviewing medical records. Results Anti-GM-CSF Ab was detected in 60% of CTD (frequencies of positivity: SLE; 70%, DM/PM; 57%, RA; 57%, vasculitis 55%) (Fig.1). PAP was not found in all cases except one SLE that has been reported previously. Neutralizing activity was not detected except the case of SLE with PAP. Pulmonary involvements including interstitial lung disease, bronchial disease and pleuritis was frequently found in RA patients positive for the Abs compared to negative patients (positive 47%, vs negative 18%; p<0.001). Similarly, pulmonary involvements were found in SLE patients with the Abs (positive 25%, vs negative 5%; p=0. 04). In DM/PM, no differences were found in frequencies of of pulmonary involvements between the Ab positive and negative groups, because more than 80% of the patients had lung involvements.Therapy decreased titers of the Ab in SLE and RA. Conclusions Non-neutralising Autoantibody against GM-CSF was frequently detected in CTD patients, particularly those with pulmonary involvements. These findings suggest that the autoantibody, which might work as carrier protein of GM-CSF, plays roles in the development of CTDs, especially pulmonary involvements in RA and SLE. Disclosure of Interest None declared
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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    Kazuhiro Kurasawa · Satoko Arai

    Preview · Article · Nov 2014
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    ABSTRACT: Background IgG4 related disease (IgG4RD) is a multi-organ affecting disease characterized by fibro-sclerosing lesions with IgG4+ cell infiltration. Serum IgG4 elevation is a critical clue for diagnosis of IgG4RD. However, there are patients of non-IgG4RDs whose IgG4 levels are elevated. Clinical features of these patients have not been fully elucidated. Objectives To clarify clinical features of patients with serumIgG4 elevation, particularly, to determine whether IgG4 RD is a distinctive disease in patients with IgG4 elevation and whether there is a subset of non-IgG4RDs which have strong similarity to IgG4RD. Methods For determination of the prevalence of patients with serum IgG4 elevation, consecutive 185 patients who admitted our department during 2 months were enrolled. For clarification of clinical features of patients with IgG4 elevation (IgG4>135mg/dl), 68 cases with IgG4 elevation were selected from consecutive 350 patients receiving IgG4 test in clinical practice at our hospital and their medical records were reviewed retrospectively. IgG4RD was diagnosed by comprehensive diagnostic criteria for IgG4-related disease (Mod Rheumatol.22:21-30; 2012). Cluster analysis according to organ involvements was performed through Ward's method. Results Prevalence of serum IgG4 elevation in general inpatients was 9/1850 (4.9%). Only 1 of 9 was IgG4RD. Among 68 cases with IgG4 elevation who received IgG4 test in clinical practice, IgG4RD was 41%. Cluster analysis according to organ involvements revealed 5 clusters; cluster1: multiple sclerosing lesions with salivary, orbital and retroperitoneal lesions, 2: sclerosing lesions with autoimmune pancreatitis, 3: pulmonary inflammation, 4 varieties of inflammatory diseases including connective tissue diseases, and 5: pleuritis. Cluster 1 and 2 were divided from other ones at 1st node. IgG4RD existed only cluster 1 and 2. In addition to sclerosing lesions, non-sclerosing lesions were found in 13% of cluster 1, 43% of cluster 2, 33% of IgG4RD and 70% of non-IgG4RDs. Non-sclerosing lesions were developed as organ limited inflammation in most cases of IgG4RD and non-IgG4RDs, which was contrast to sclerosing lesions in IgG4RD affecting multi-organs. Among non-sclerosing lesions, IgG4+ cells were observed. Pathological examination of non-sclerosing lesions revealed IgG4+ cell inflammation in 4/5 in IgG4RD and 8/21 in I non-IgG4RDs. The lesions in non-IgG4RDs were indistinguishable from those in IgG4RD. Patients of non-IgG4RDs with IgG4+ cells had similar clinical features to IgG4RD including high IgG4 levels, low CRP levels and good response to glucocorticoid in addition to pathological findings. Conclusions IgG4RD is a minor, but a distinctive disease in patients with serum IgG4elevation, characterized by sclerosing lesions affecting multiple organs. IgG4RD causes non-sclerosing lesions with IgG4+ cells as well as sclerosing ones. Among non-IgG4RDs, there are patients with IgG4 + non-sclerosing lesions indistinguishable from those of IgG4RD and they had similar clinical features to IgG4RD. It might be necessary to provide a position to these cases in “the extended spectrum of IgG4RD” defined as having IgG4+ cell inflammation and serum IgG4 elevation. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4032
    No preview · Article · Jun 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background Organizing pneumonia (OP), different name: bronchiolitis obliterans with organizing pneumonia (BOOP), is a form of interstitial lung diseases characterized by presence of buds of granulation tissue in bronchiole and alveoli. Radiographic feature of OP is diffuse alveolar opacities which are similar to bacterial pneumonia and tumors. There are two types of OP; cryptogenic OP and secondary OP. Secondary OP is associated with many entities such as infection, drugs and connective tissue diseases including RA. However, clinical features of OP in patients with RA remain unclear Objectives To clarify clinical features of OP associated with RA, particularly, to determine whether the development of OP is related to disease activity of arthritis. Methods To determine prevalence of OP, we reviewed medical records of consecutive 499 RA patients who visited our hospital in Dec 2010. For analysis of clinical features of OP, we analyzed medical records of 24 RA patients with OP; 19 extracted by the above screening and additional 5 who admitted our hospital because of OP in 2011-12. OP was diagnosed by pathological findings or typical pulmonary imaging with clinical features (migration pulmonary infiltrates/ no response to antibiotics and good response to glucocorticoid). Results Among 499 RA patients, patients with history of OP were 19 (3.8%) cases, while prevalence of interstitial pneumonia and with bronchoectasia/bronchiolitis were 13.0% and 6.0%, respectively. Among 24 patients, male was8 and female was 16. Age of the onset of OP was 60.5 ± 9.6 year (mean ± sd). RA preceded OP in 16 patients (67%), while OP developed simultaneously with RA in 3 patients, and occurred before the onset of RA in 3 cases. The interval between the onset of RA and OP was 11.6 ± 12.8 years. Positivity of RF and anti-CCP antibody were found in 18/24 and 14/17, respectively. At the onset of OP, 18 patients were treated for RA, 11 and 7 of them received MTX and d TNF inhibotors, respectively. The disease activity of RA was high in 4, moderate in4, low in 9, and CR in 1 case. Only 3 patients showed exacerbation of arthritis. Respiratory symptoms and fever were found in 14 and 18 out of 24 OP patients. All patients revealed alveolar opacities, multiple lung lesions were found in half of the cases, and spontaneous resolution of the lung infiltrates was found in 9 cases. antibiotics weres ineffective for OP and glucocorticoid dramatically improved OP. Relapse of OP was found in 5 patients without exacerbation of arthritis. Conclusions OP is not a rare pulmonary complication in RA which develops in 4% in RA. OP develops in patients whose disease activity was controlled or in those treated with TNF inhibitors, successfully. These findings suggest that OP in RA might be TNF- independent and have different pathogenesis from arthritis. Disclosure of Interest None Declared
    No preview · Article · Jan 2014 · Annals of the Rheumatic Diseases

  • No preview · Article · Sep 2013 · Modern Rheumatology
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    ABSTRACT: Objective: The aim of this study is to determine whether serum KL-6 and surfactant protein D (SP-D) levels predict the prognosis of patients with interstitial pneumonia (IP) in cases of polymyositis (PM) and dermatomyositis (DM). Patients and methods: Fifty consecutive patients with PM (n = 17) or DM (n = 33) and active IP, 6 of whom died of respiratory failure, were enrolled in this study. Serum KL-6 and SP-D levels were measured every 2-4 weeks. Medical records were reviewed retrospectively. Univariate analyses and multivariate analyses with a logistic regression model were conducted. Results: Serum KL-6 and SP-D levels were elevated in patients with active IP. At the time of diagnosis of active IP, the serum KL-6 level was within the normal range in 28 % of patients and the SP-D level was within the normal range in 46 % of patients. Serum KL-6 level increased up to 3 months after starting treatment and then decreased gradually to baseline, whereas SP-D level peaked within the first 4 weeks after treatment and decreased rapidly to normal levels. Patients with poor prognosis showed increases in KL-6 and SP-D levels during the first 4 weeks after treatment, which was confirmed by uni- and multivariate analyses. Comparing the marker levels at 2-4 weeks after treatment with those at 0 weeks, an increase in the ratio over 1.70 for KL-6 and over 1.75 for SP-D, and an increase in KL-6 over 850 U/ml during the first 4 weeks after treatment, were poor prognostic factors. Conclusions: Increases in serum KL-6 and SP-D levels during the first 4 weeks after starting therapy, but not their levels at any one time point, predict poor prognosis in patients with PM/DM. When marked increases of KL-6 and SP-D levels during the first 4 weeks are found or are predicted by serial measurement of the markers, patients have risks of poor prognosis and additional therapy should be considered.
    No preview · Article · Sep 2012 · Modern Rheumatology
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    ABSTRACT: To evaluate the usefulness of F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging in the management of patients with inflammatory myopathy. We examined whether FDG-PET scanning detects myositis or extramuscular lesions in patients with polymyositis (PM) and dermatomyositis (DM). FDG-PET imaging was performed in 24 patients with active inflammatory myopathy (PM, 11; DM, 13). The images were read by radiologists in a blinded manner. FDG uptake into muscles was judged positive when the intensity of muscles was higher than or equal to that of the liver. As controls, FDG imaging findings of patients with a lung mass and without muscle diseases were used. To investigate associations between FDG-PET findings and clinical/laboratory findings, the patients' medical records were reviewed retrospectively. Increased FDG uptake in muscles was found in 8 of 24 (33%) patients. In 67 of 69 (97%) controls without muscle diseases, no muscle FDG uptake was detected. The sensitivity of FDG-PET to detect myositis was lower than that of electromyogram (EMG), magnetic resonance imaging, and muscle biopsy. There were no significant differences in clinical manifestations between patients with and without increased FDG uptake in muscles, although patients with FDG muscle uptake had a tendency to have extended myositis with endomysial cell infiltration. FDG-PET detected neoplasms in patients with associated malignancy. FDG uptake in lungs was found in 7 of 18 patients with interstitial lung disease. FDG-PET imaging has limited usefulness for the evaluation of myositis in patients with PM/DM because of its low sensitivity, although it might be useful for detection of malignancy in these patients.
    No preview · Article · Jul 2012 · The Journal of Rheumatology
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    ABSTRACT: OBJECTIVES: Trimethoprim-sulphamethoxazole (TMP-STX), an agent used for prophylaxis against pneumocystis pneumonia (PCP) in immunocompromised hosts, causes serious adverse effects (AEs) in some patients. The objective of this study was to identify the risk factors for AEs caused by TMP-STX in connective tissue disease (CTD) patients and to describe the clinical features of the AEs. METHODS: The medical records of 539 patients (CTDs 312, pulmonary diseases 227) receiving TMP-STX for prophylaxis against PCP were reviewed retrospectively. Patients with human immunodeficiency virus were excluded. Univariate and multivariate analyses were conducted to identify the risk factors. RESULTS: Adverse events caused by TMP-STX occurred in 22 of 312 (7.05 %) CTD patients, while only six of 227 (2.64 %) pulmonary disease patients developed AEs. The incidence of AEs was significantly higher in systemic lupus erythematosus (SLE) (11.0 %) and mixed connective tissue disease (MCTD) (33.3 %) patients than in other CTD patients. AEs occurred in 25 % of patients with anti-RNP antibody. Univariate analysis revealed that SLE, MCTD, and anti-RNP antibody were risk factors for AEs in CTD patients. Further multivariate analyses demonstrated that only anti-RNP antibody positivity was a risk factor for AEs. Systemic inflammation, including fever, was a characteristic manifestation of the AEs in CTD patients, particularly those with anti-RNP antibody. CONCLUSIONS: Positivity for anti-RNP antibody is a risk factor for AEs caused by TMP-STX in CTD patients. Systemic inflammation, including fever, might be a characteristic feature of the AEs in CTD patients, particularly those with anti-RNP antibody.
    No preview · Article · Mar 2012 · Modern Rheumatology
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    ABSTRACT: Reactivation of cytomegalovirus (CMV) occurs during intensive immunosuppressive therapies. However, the influence of CMV reactivation on prognosis in patients with immunosuppressive therapies for collagen-vascular diseases (CVD) is not fully understood. To determine whether CMV reactivation affects the prognosis of patients with CVD and to identify risk factors of CMV reactivation, we reviewed, retrospectively, the medical records of 109 CVD patients who were treated with glucocorticoid (prednisolone ≥20 mg/day) and were tested for CMV antigen (CMV-Ag). CMV-Ag was detected in 34 of the 109 patients. First-time CMV-Ag detection was within 50 days from the start of intensive immunosuppressive therapy in 82% of the patients. Common manifestations at first-time CMV-Ag detection were fever, arthralgia, and rash, although 52.9% of the patients were asymptomatic. The risk factors for CMV reactivation were old age (>65 years) and high-dose glucocorticoids (PSL ≥50 mg). During the 4-year study period, 18% of patients with positive CMV-Ag and 5% of those without CMV-Ag died. Patients with CMV-Ag (max CMV number ≥5/10(5) WBC) had a significantly poorer prognosis. Multivariate analysis confirmed CMV reactivation as an independent poor prognostic factor in CVD patients. Causes of death were exacerbation of pre-existing interstitial pneumonia and infection other than CMV. Our results demonstrate that CMV reactivation, particularly with a high CMV-Ag number, is a poor prognostic factor in CVD patients. Patients with older age and high-dose glucocorticoids have a high risk of CMV reactivation.
    No preview · Article · Sep 2011 · Modern Rheumatology
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    ABSTRACT: A 58-year old Japanese woman who had been diagnosed with and managed for systemic sclerosis (SSc) with pulmonary arterial hypertension died suddenly. However, the autopsy revealed marked right ventricular dilatation, and the myocardium had been replaced by fatty tissue. These findings were consistent with arrhythmogenic right ventricular dysplasia (ARVD). A literature search identified nine cases of SSc with ARVD in Japan, including this case; this number is significantly higher than the value estimated from the prevalences of ARVD and SSc in Japan, suggesting an association between these two rare diseases.
    No preview · Article · Jun 2011 · Modern Rheumatology
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    ABSTRACT: Autoantibody against platelet-derived growth factor receptors (PDGFRs) has been reported in scleroderma (SSc). However, it remains unknown whether anti-PDGFRs antibody exists in collagen vascular diseases other than SSc. To answer the question, we developed an ELISA system and examined sera from patients with SLE (n = 75), SSc (n = 31), RA (n = 25) and control individuals. We also reviewed medical records to clarify clinical features of patients with anti-PDGFRα antibody. To examine the functions of anti-PDGFRα antibody in patients, fibroblasts were cultured and stimulated in the presence of purified IgG from patients, and their cell numbers were counted. Anti-PDGFRα antibody was detected in 29% of patients with SLE and in 21% of patients with SSc. Anti-PDGFRα antibody was found in 36% with active SLE, but in 10% in an inactive phase. Immunosuppressive therapy decreased the titer of the antibody. Patients with anti-PDGFRα antibody frequently developed a rash and hematological abnormalities, particular hemolytic anemia. Moreover, anti-PDGFRα antibody in SLE failed to demonstrate agonistic or antagonistic activities on PDGFR signaling. These findings indicate that nonfunctional anti-PDGFRα autoantibody exists in patients with SLE as well as those with scleroderma, and that the antibody could be a marker of disease activity and may be a marker of a subgroup of SLE.
    No preview · Article · Oct 2010 · Modern Rheumatology
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    ABSTRACT: To be clear the clinical characteristics in Tochigi, we analyzed patients with HIV infection in our department. Patients with HIV infection between July 2002 and June 2009 were 34 subjects (Man: Woman 27: 7, Japanese: Foreigner 29: 5), and mean age was 44.2 years old. In reason of HIV infection for men, men who were infected by sexual intercourse with indefinite women were 40.7% and men who were infected by sexual intercourse with men were 37.0%. Women who were infected by their partners were 57.1%. 64.7% of patients were recognized HIV infection by showing AIDS. 79.4% of patients already had complications indicating AIDS, when they came to our hospital, and 55.9 % of patients had pneumocystis jiroveci pneumonia. In 97.1 % of patients, the number of CD4 positive cells were under 350/μl. In conclusion, around 70% of patients were recognized HIV infection before they become AIDS in Japan. But, a large majority of patients in our department were with becoming AIDS or just before AIDS. We need to develop the system of early intervention for HIV infection.
    No preview · Article · Mar 2010
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    ABSTRACT: We report the case of a patient with systemic lupus erythematosus (SLE) who first revealed hemophagocytic syndrome (HPS), which was treated successfully with glucocorticoid and intravenous cyclophosphamide. The patient then demonstrated refractory thrombotic thrombocytopenic purpura (TTP) with normal a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)-13 activity that responded well to rituximab. After rituximab treatment, the patient showed a flare of HPS that was controlled by additional intravenous cyclophosphamide treatment. This case showed that TTP with normal ADAMTS-13 activity is B-cell dependent and indicated that B-cell depletion might exacerbate some autoimmune conditions in SLE.
    No preview · Article · Sep 2009 · Modern Rheumatology