Masuyuki Nawata's scientific contributionswhile working at Juntendo University (Tokyo, Japan) and other institutions

Publications (22)

Publications citing this author (344)

    • Epitope mapping studies using SLE patient sera [15,16] have revealed that nearly the full-length protein is required for antibody binding [17] suggesting that the critical epitope is conformational and/or discontinuous [16]. Autoantibodies targeting PCNA occur in b5% of SLE patients and have been reported to be a specific biomarker for this disease [8,181920 (reviewed in [1]).
    [Show abstract] [Hide abstract] ABSTRACT: Autoantibodies targeting the proliferating cell nuclear antigen (PCNA) were first described over 30 years ago and are historically most commonly associated with systemic lupus erythematosus (SLE). The primary antigenic target is a 34 kDa protein that is part of the DNA polymerase delta multi-protein complex. A number of diagnostic platforms have incorporated PCNA into their diagnostic assays and algorithms. However, little is known about the clinical utility of autoantibodies to PCNA, especially with novel detection systems. This review will focus on the history of the discovery of the PCNA autoantigen and the current status of the diagnostic significance of anti-PCNA and suggest future studies that are required to strengthen our understanding of their clinical utility.
    Full-text · Article · Feb 2012
    • Direct destruction of adrenocortical cells by virus infection , immune mediated destruction by cross-reacting T cells or non-specific enhancement of antigen presentation has been suggested to be the underlying pathogenic mechanisms [35]. CMV infection is one of the most common viral infections throughout the world and has been associated with a number of autoimmune diseases , including systemic lupus erythematosus (SLE), T1D, vasculitis and Sjögren's syndrome [16, 21, 36, 37]. Even though a healthy immune system controls CMV infection, the virus can never be eliminated by immune effector mechanisms or antiviral drugs.
    [Show abstract] [Hide abstract] ABSTRACT: Autoimmune Addison’s disease (AAD) is caused by multiple genetic and environmental factors. Variants of genes encoding immunologically important proteins such as the HLA molecules are strongly associated with AAD, but any environmental risk factors have yet to be defined. We hypothesized that primary or reactivating infections with cytomegalovirus (CMV) could represent an environmental risk factor in AAD, and that CMV specific CD8 + T cell responses may be dysregulated, possibly leading to a suboptimal control of CMV. In particular, the objective was to assess the HLA-B8 restricted CD8 + T cell response to CMV since this HLA class I variant is a genetic risk factor for AAD. To examine the CD8 + T cell response in detail, we analyzed the HLA-A2 and HLA-B8 restricted responses in AAD patients and healthy controls seropositive for CMV antibodies using HLA multimer technology, IFN-γ ELISpot and a CD107a based degranulation assay. No differences between patients and controls were found in functions or frequencies of CMV-specific T cells, regardless if the analyses were performed ex vivo or after in vitro stimulation and expansion. However, individual patients showed signs of reactivating CMV infection correlating with poor CD8 + T cell responses to the virus, and a concomitant upregulation of interferon regulated genes in peripheral blood cells. Several recently diagnosed AAD patients also showed serological signs of ongoing primary CMV infection. CMV infection does not appear to be a major environmental risk factor in AAD, but may represent a precipitating factor in individual patients.
    Full-text · Article · Dec 2016
    • Hemophagocytic syndrome is a life-threatening hyperinflammatory syndrome where there is phagocytosis of red blood cells, leukocytes, platelets, and their precursors in the bone marrow and other tissues. It may be secondary to autoimmune diseases; however, its association with APS is extremely rare[77].
    [Show abstract] [Hide abstract] ABSTRACT: The association between antiphospholipid antibod-ies (aPL) and clinical problems goes beyond what is stated in the antiphospholipid syndrome (APS) classification criteria, namely thrombosis and pregnancy morbidity, and thrombocy-topenia is the most common non-criteria hematologic manifestation of aPL with a frequency ranging from 20 to 50 %. Thrombocytopenia is rarely severe, and hemorrhage is far less common than thrombosis. However, when anticoagulation is considered, it may constitute a clinical problem with increased bleeding risk. Furthermore, thrombocytopenia represents a risk factor for thrombosis in aPL-positive patients. Therefore, it is important to understand the pathogenesis and the clinical associations of thrombocytopenia to build the right medical approach in aPL-positive patients. In this paper, we review the literature on aPL/APS-associated thrombocytopenia and briefly discuss the other conditions that can result in thrombocyto-penia as they have commonalities with APS and their recognition is important to establish the most appropriate treatment strategy.
    Full-text · Article · Mar 2015
    • The increase in hygiene could reduce infections that are either pathogenic or protective in SLE. Known triggers of lupus development include parvovirus B-19[8], rubella virus[9], Epstein-Barr virus and cytomegalovirus (CMV)[7,[10][11][12][13][14][15]. Infectious agents that have been shown to be protective against SLE, on the other hand, include Helicobacter pylori, hepatitis B virus (HBV), Toxoplasma gondii, malaria parasites such as Plasmodium berghei and Plasmodium chabaudi and more recently described, helminths.
    Chapter · May 2017 · Journal of Cellular and Molecular Medicine
    • By using a single CCP as the antigen in an ELISA test, anti-CCP antibody is as sensitive as and more specific than RF in early rheumatoid arthritis11121314. However, the sensitivity and specificity described in the different studies are dependent on the cutoff titre chosen for test positivity, the characteristics of the arthritis population in which the test is used, and the gold standard chosen for RA; they vary from 30 to 70% and from 91 to 99%, respectively [15, 16]. Anti-Sa antibodies are another member of the family of antibodies directed to citrullinated proteins and were originally identified in a French Canadian patient with RA, and this reactivity was found to be highly specific for RA [17].
    [Show abstract] [Hide abstract] ABSTRACT: Conventional tests are not always helpful in making a diagnosis of rheumatoid arthritis (RA). This study aimed to comprehensively and quantitatively summarize the evidence on the accuracy of anti-mutated citrullinated vimentin (MCV) assay in the diagnosis of RA. A comprehensive meta-review of data on the accuracy of MCV concentrations in the diagnosis of RA were carried out from 16 published studies. Furthermore, receiver operating characteristic curves were used to summarize the overall test performance. The summary estimates for MCV in the diagnosis of RA were: sensitivity 0.77 [95% confidence interval (CI) 0.75-0.78], specificity 0.89 (95% CI 0.87-0.90), positive likelihood ratio (LR+) 7.24 (95% CI 5.60-9.36), negative likelihood ratio (LR-) 0.28 (95% CI 0.23-0.34) and diagnostic odds ratio 29.66 (95% CI 21.09-41.71). The area under the summary receiver operating characteristic curves was 0.92. Data from meta-analysis suggest the accuracy of MCV assay in the diagnosis of RA is high, but ultimately clinician must consider the results of MCV tests combing with other conventional examinations and the clinical feature.
    Article · Mar 2010
    • In addition to the correlation analyses with well-known biomarkers, PA28γ serum levels were compared with anti-PA28γ autoantibody levels. These autoantibodies were detected in several autoimmune disorders including SLE and SS [41]. Our results indicate a significant connection between PA28γ protein levels and anti-PA28γ autoantibody levels even in RA sera.
    [Show abstract] [Hide abstract] ABSTRACT: PA28gamma (also known as Ki, REG gamma, PMSE3), a member of the ubiquitin-and ATP-independent proteasome activator family 11S, has been proved to show proteasome-dependent and -independent effects on several proteins including tumor suppressor p53, cyclin-dependent kinase inhibitor p21 and steroid receptor co-activator 3 (SCR-3). Interestingly, PA28gamma is overexpressed in pathological tissue of various cancers affecting e. g. breast, bowl and thyroids. Furthermore, anti-PA28gamma autoantibodies have been linked to several autoimmune disorders. The aim of this study was to develop and evaluate a novel and sensitive PA28gamma sandwich ELISA for the quantification of PA28gamma serum levels in patients with cancer and autoimmune diseases for diagnostic and prognostic purposes. PA28gamma-specific polyclonal antibodies and recombinant His-tagged PA28gamma were purified and used to develop a sandwich ELISA for the detection of circulating PA28gamma. With this new assay, PA28gamma serum levels of patients with various cancers, rheumatoid arthritis (RA), Sjogren's syndrome (SS), adult-onset Still's disease (AOSD) and different connective-tissue diseases (CTD) were compared with healthy control subjects. Anti-PA28gamma autoantibodies were additionally confirmed using a newly developed microbead assay. The developed PA28gamma sandwich ELISA showed a high specificity with a detection limit of 3 ng/ml. A significant up-regulation of circulating PA28gamma was detected in the sera of patients with cancer, RA, SS and CTD. A significant correlation was observed dependent on age as well as anti-PA28gamma autoantibody levels with circulating PA28gamma protein levels. Furthermore, PA28gamma serum levels showed a correlation with disease activity in patients with RA under treatment with the T-cell directed biological compound abatacept according to disease activity score 28 (DAS28) and erythrocyte sedimentation rate (ESR). The application of PA28gamma as a novel biomarker for diagnostic purposes of a specific disease is limited, since elevated levels were observed in different disorders. However, the correlation with disease activity in patients with RA suggests a prognostic value, which needs to be addressed by further studies. Therefore our results show that PA28gamma is a useful marker which should be included in studies related to novel treatments, e.g. abatacept.
    Full-text · Article · Dec 2014
    • In the SLE patients, it is reported that the clinical use of glucocorticoid or other immunosuppressants, multiple antibiotics and steroidinduced diabetes always contributed to the dysfunction of immune response . And the dysfunction of immune cells including T cell, B cell and dendritic cell was demonstrated to promote SLE patients more susceptible for the occurrence of IFI (Nambiar et al., 2002; Nevzorova et al., 2006; Ramanujam et al., 2004; Reefman et al., 2007; Seta et al., 2002; Takeuchi, 2002; Traustadottir et al., 2002). Therefore, it is believed that the imbalancement of immune response of host be capable of increasing the risk for the incidence of IFI (Petri and Genovese, 1992).
    [Show abstract] [Hide abstract] ABSTRACT: Invasive fungal infection (IFI) is a life-threatening infection occurring most often in patients with systemic lupus erythematosus (SLE) and few data has been reported in SLE patients particularly in China. This present study was aimed to determine IFI prevalence, associated risk factors and patterns of infection in Chinese SLE patients. A retrospective study was conducted in a single institute of Northern China from July 2004 and October 2010. Demographic characteristics, clinical and laboratory data, and mycological examinations were collected. Among 1534 patients included, 20 (1.6%) were diagnosed with IFI, of whom there were 18 females and 2 males with the average age of 35.4 ± 15.1 years old. Involved sites included nine lungs, six central nervous system and five disseminated cases. 6 of 20 IFIs cases (30%) were non-survivors including 2 lungs, 2 central nervous system and 2 disseminated cases. Compared with survivors, non-survivors had significantly higher equivalent prednisone doses, elevated level of serum C reactive protein (CRP), higher erythrocyte sedimentation rate (ESR), higher thrombocytopenia rate and higher systemic lupus erythematosus disease activity index (SLEDAI) score. These results strongly demonstrated that prednisone doses, CRP, ESR, thrombocytopenia and SLEDAI could be associated risk factors in the prognosis of SLE patients with IFI.
    Full-text · Article · Jun 2012
    • GAPDH is a classical glycolytic enzyme involved in energy production, but it is also implicated in numerous important cellular pathways including receptor-mediated cell signalling, transcriptional and post-transcriptional gene regulation , maintenance of DNA integrity, oxidative stress response and apoptosis [99]. In patients with SLE, GAPDH was found to interact with proliferating cell nuclear antigen, a known autoantigen targeted by antibodies, indicating its possible role in autoimmune responses induction against proliferating cell nuclear antigen complexes in SLE [100]. In addition, alpha-enolase was identified as a candidate antigen in proliferative LN forms [11] and was upregulated in SLE PBMCs compared with healthy controls [24].
    [Show abstract] [Hide abstract] ABSTRACT: Advances in mass spectrometry technologies have created new opportunities for discovering novel protein biomarkers in systemic lupus erythematosus (SLE). We performed a systematic review of published reports on proteomic biomarkers identified in SLE patients using mass spectrometry-based proteomics and highlight their potential disease association and clinical utility. Two electronic databases, MEDLINE and EMBASE, were systematically searched up to July 2015. The methodological quality of studies included in the review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Twenty-five studies were included in the review, identifying 241 SLE candidate proteomic biomarkers related to various aspects of the disease including disease diagnosis and activity or pinpointing specific organ involvement. Furthermore, 13 of the 25 studies validated their results for a selected number of biomarkers in an independent cohort, resulting in the validation of 28 candidate biomarkers. It is noteworthy that 11 candidate biomarkers were identified in more than one study. A significant number of potential proteomic biomarkers that are related to a number of aspects of SLE have been identified using mass spectrometry proteomic approaches. However, further studies are required to assess the utility of these biomarkers in routine clinical practice.
    Full-text · Article · Nov 2016
    • For some recurrence and toxic treatment cases, CTX may not be successful. Naoto Tamura reported that the use of Rituximab MabThera (CD20 mouse chimeric monoclonal antibody) to consume beta cells was valuable for recurrence cases, and this drug can reduce the titer of ANCA; moreover, hormone dosage is reduced without any side effects[18]. Surgical treatment should be performed with caution because the symptoms may worsen after myringotomy and mastoidotympanectomy. Up to 25 recently reported cases were successfully treated by drugs without surgery[4].
    [Show abstract] [Hide abstract] ABSTRACT: Wegener's granulomatosis (WG) is an autoimmune disease characterized by necrotizing granulomatous vasculitis. The causes of WG are unclear, and all body systems can be affected by this disease. The diversity of WG indications often causes misdiagnosis. This paper reports a type of rapid WG case, in which otitis media emerged and developed into unilateral facial paralysis, as well as caused many organ lesions in the nose, heart, liver, and kidney.
    Full-text · Article · Jan 2016 · Journal of Cellular and Molecular Medicine