Shinsuke Yasuda

Hokkaido University Graduate School of Medicine · Division of Rheumatology, Endocrinology and Nephrology

Background Idiopathic inflammatory myopathy (IIM) includes heterogeneous phenotypes such as polymyositis (PM), dermatomyositis (DM), and antisynthetase syndrome. The underlying mechanisms of muscle damage remain poorly understood. Objectives The aim of this study was to investigate the transcriptome and immunophenotypic features of muscle biopsies...

Objective To assess cost-effectiveness of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) in rheumatoid arthritis. Methods We conducted 3 analyses: a lifetime analysis with a cohort model (study A) and 2 short-term analyses (studies B and C). Study A evaluated the incremental cost-effectiveness ratio (ICER) per...

Objective: No evidence has shown the efficacy of Sodium Risedronate (Risedronate) for glucocorticoid-induced osteoporosis (GIO) in patients with Rheumatoid arthritis (RA). The aim of this study was to explore the effectiveness and safety of Risedronate for GIO complicated with RA. Methods: This was a six-month randomized, double-blind, placebo-cont...

Objective Optineurin (OPTN) is an autophagy adaptor/receptor that acts as an intrinsic negative regulator of osteoclast differentiation. RANKL expressed by rheumatoid arthritis synovial fibroblasts (RASFs) is primarily responsible for the development of bone erosions in patients with RA. The aim of the present study was to explore the role of OPTN...

Objective This study aimed to explore the risk factors for ‘severe’ neuropsychiatric (NP) flare in patients with systemic lupus erythematosus (SLE). Methods This retrospective study comprised newly diagnosed 184 adult SLE patients who visited Hokkaido University Hospital between 2006 and 2017. In this study, severe NP flare was defined as the occu...

IntroductionAntiresorptive agent-related osteonecrosis of the jaw (ARONJ) is a rare but serious complication in patients receiving antiresorprtive agents (AR). However, the incidence of ARONJ after tooth extraction in patients with autoimmune disease (AID) remains unclear. The present study aimed to clarify the high-risk population of ARONJ in pati...

Objective: Rapidly progressive interstitial lung disease (RPILD) is a major cause of death in patients with DM. Although clinically amyopathic DM (CADM) represents risk for RPILD, the incidence rate of RPILD in patients with CADM varies widely. Whole-body (WB) MRI can reveal involvement of systemic muscle and myofascia. The objective of this study...

Objectives: We evaluated long-term control of rheumatoid arthritis (RA) in Japanese paid workers (PWs) and house workers (HWs) treated with subcutaneous tocilizumab (TCZ-SC) and explored factors affecting response to TCZ-SC regarding work productivity. Methods: This study collected data from patients with RA in the TCZ-SC +/− conventional synthetic...

Objective The objective of this study was to clarify the efficacy and safety of factor Xa inhibitors for antiphospholipid syndrome patients in real world utilization. Methods This is a retrospective cohort study comprised of all consecutive patients with antiphospholipid syndrome in our department over a period of 28 years. Patients treated with f...

Objectives We aimed to evaluate the obstetric complications and the risk factors for these events in pregnant women with rheumatic diseases (RDs). Methods A single-center retrospective study of women with RDs at Hokkaido University Hospital between 2007 and 2016 was conducted. Clinical features and maternal and fetal outcomes were retrospectively...

We aimed to investigate the involvement of macroautophagy/autophagy in autoimmunity in rheumatoid arthritis (RA) through citrullination of VIM (vimentin) and its interaction with MHC class II in synovial fibroblasts (SFs). The cell surface expression of MHC class II and B7 costimulatory molecules on SFs was analyzed by flow cytometry after treatmen...

Objectives: Pulmonary hypertension (PH) in patients with CTD is a heterogeneous condition affected by left heart disease, chronic lung disease and thromboembolism as well as pulmonary vascular disease. Recent studies using cardiac magnetic resonance (CMR) have shown that right ventricular dysfunction is predictive for mortality in patients with PH...

Early intervention in pulmonary arterial hypertension associated with systemic sclerosis (SSc) may improve its prognosis. We aimed to establish an algorithm to detect mean pulmonary artery pressure (mPAP) > 20 mmHg using non-invasive examinations in SSc patients by modifying the DETECT algorithm. This study included SSc patients who underwent right...

Objective: Warfarin is regarded as the standard treatment for preventing thrombotic events in APS, but the recurrence rate is still high. Dual antiplatelet therapy (DAPT) has been shown to be effective for the prevention of acute coronary syndrome or stroke. The objective of this study was to evaluate the efficacy of DAPT for the prevention of thr...

Background Rapidly progressive interstitial lung disease (RPILD) is a major cause of death in patients with dermatomyositis (DM). Early diagnosis and aggressive immunosuppressive therapy are required in RPILD to improve the prognosis. Clinically amyopathic dermatomyositis (CADM) and anti-melanoma differentiation-associated gene 5 antibody are known...

Background Rheumatoid arthritis (RA) is a major cause of work disability, sickness-related absence from work, presenteeism, and loss of productivity. The decrease in work productivity that results from persistent pain, impaired mobility and function, and reduced quality of life (QOL) has important personal, societal, and economic consequences[1]. T...

Objective: Idiopathic osteonecrosis of the femoral head (ION) is a common complication of SLE associated with CS therapy. Although the pathogenesis of ION involves local bone ischaemia favoured by thrombophilia, the involvement of aPL in lupus ION remains to be elucidated. We have previously reported the aPL score (aPL-S) as a quantitative marker...

Recurrent pregnancy loss (RPL) is often considered idiopathic, however excessive complement activation has been observed in pregnancy related manifestations. Anti-C1q antibodies (anti-C1q) are associated with the activation of complement pathway in lupus patients, while it remains unclear in RPL. Firstly, we showed that both the prevalence and titr...

Rationale: Neutrophil extracellular traps (NETs) are immune defence systems that release extracellular chromatin and myeloid granules including myeloperoxidase (MPO) to kill pathogens. An experimental animal study recently demonstrated that disordered NETs induced by propylthiouracil (PTU) could contribute to the production of MPO anti-neutrophil...

Background/Objective Antiphospholipid antibodies (aPL) are pathogenic autoantibodies in antiphospholipid syndrome (APS). This study aimed to clarify the mechanism of aPL production. Methods T cell and B cell subsets were evaluated in peripheral blood mononuclear cells (PBMCs) of 26 primary APS (PAPS), 19 systemic lupus erythematosus‐associated APS...

Objectives. To analyze the effects of tocilizumab on peripheral B-cell subpopulation and its ability to produce anti-cyclic citrullinated peptide (CCP) antibody in patients with rheumatoid arthritis (RA). Methods. Thirteen consecutive RA patients initiated with tocilizumab were enrolled in our prospective study. Anti-CCP antibody titers and clinica...

Objectives: Thrombocytopenia is frequently observed in antiphospholipid antibody (aPL) carriers. Due to the paradoxical risks of thrombosis and hemorrhage, the management of aPL-associated thrombocytopenia (APAT) is often deductive. We aimed to investigate the efficacy and safety of therapeutic approaches for APAT through a systematic review. Metho...

Rationale: An association between inflammatory myopathy and malignancy has been recognized particularly in patients positive for anti-transcription intermediary factor 1γ (TIF1γ) antibody. We report a case of anti-TIF1γ antibody positive dermatomyositis (DM) associated with thymic carcinoma which radiographically mimicked benign tumor. Patient co...

Background Anti‐DNA/N‐methyl‐D‐aspartate receptor 2 (NR2) antibodies (anti‐DNA/NR2 antibodies) are a subset of anti‐DNA autoantibodies that cross‐react with the extracellular domain of the GluN2A/GluN2B subunits of NR2. These antibodies induce apoptosis of hippocampus neurons and psychiatric disorder in mice and humans. Neuropsychiatric system lupu...

Objectives Rheumatoid arthritis (RA) is an autoimmune polyarthritis, in which fibroblast-like synoviocytes (FLS) play a key role in cartilage and bone destruction through tumour-like proliferation and invasiveness. Considering still unsatisfactory remission rate in RA even under treatment with biological disease-modifying antirheumatic drugs, novel...

To date, numerous genetic and epigenetic studies have been performed and provided a crucial step forward in our understanding of the pathogenesis of rheumatic diseases. However, most of the recent advances in the treatment of rheumatic diseases including biological therapies are not based on or even discrepant from these genetic and epigenetic find...

Background: Following the onset of rheumatoid arthritis (RA), patients experience a functional decline caused by various joint symptoms which affects their activities of daily living and can lead to reduced work productivity. We evaluated the effect of a 52-week treatment with tocilizumab by subcutaneous injection (TCZ-SC) among biologic-naive Jap...

Objective T cells from SLE patients have reduced protein levels of RasGRP1, a guanine nucleotide exchange factor for Ras, and increased transcript of alternatively spliced (AS) forms lacking exon 11. Serine/arginine‐rich splicing factor 1 (SRSF1) binds pre‐mRNA to regulate AS forms of several genes, including CD3ζ in SLE T cells. This study aimed t...

Background Subclinical and overt lung diseases associated with rheumatoid arthritis (RA-LD) are present in 30%–50% of the patients. Early and effective intervention improved joint prognosis in RA. By contrast, lung complications are still the primary contributors to premature deaths in patients with RA. Lung complication in RA can be due to a varie...

Background Antiphospholipid antibodies (aPL) as pathogenic autoantibodies in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are supported by a number of clinical, ex vivo and animal studies. Nevertheless, aPL are not eliminated by corticosteroid administration or immunosuppression. Novel therapy targeting aPL production is c...

Background Adult-onset Still’s disease (AOSD) is a systemic inflammatory disorder generally responsive to corticosteroid therapy, whereas refractory AOSD is often encountered that not controlled by corticosteroid monotherapy. In such cases, methotrexate and biologics including TNF-α, IL-1, or IL-6 inhibitors are used.¹ However, more treatment optio...

Background: Premature atherosclerosis is one of the major complications of systemic lupus erythematosus (SLE). Recently, the biological linkage between atherosclerosis and osteoporosis has garnered much attention. The aim of this study is to explore correlation between the development of atherosclerosis and anti-osteoporotic treatment. Methods:...

Introduction: Although complement activation has been proposed as a possible thrombophilic mechanism in antiphospholipid syndrome (APS), the origin of complement activation in APS remains unclear. Here, we focused on complement regulatory factors (CRF), which control the complement system to prevent damage to host tissue. We evaluated the function...

Objectives: To elucidate the efficacy and safety of autologous haematopoietic stem cell transplantation (HSCT) for Japanese patients with systemic sclerosis (SSc). Methods: A phase II clinical trial included SSc patients diagnosed within the last three years having at least one of the following clinical features: diffuse skin sclerosis with modi...

Objectives: Presepsin (PSEP: soluble CD14 subtype) is produced from bacteria-stimulated monocytes or neutrophils, thus recognized as a biomarker of sepsis. Aberrant functions in monocyte or neutrophils are increasingly recognized in systemic lupus erythematosus (SLE). We investigated whether plasma PSEP reflects disease activity in patients with SL...

Objectives: The aim of this study was to clarify the consequences of Mx1, one of the IFN-inducible proteins, in the peripheral blood as well as in renal tissues in patients with systemic lupus erythematosus (SLE). Patients and methods: Mx1 protein concentrations in (PBMCs) from 18 SLE patients mostly in their stable disease status, 11 IgA nephropat...

Objective: DWEYS-IgG cross-reactive with DNA and the N-methyl-D-aspartate receptor subunits GluN2A/GluN2B has been associated with neuropsychiatric systemic lupus erythematosus (NPSLE). DWEYS-IgG has not been investigated in demyelinating NPSLE (dNPSLE) or in another demyelinating disorder, Neuromyelitis Optica Spectrum Disorder (NMOSD), which is...

We investigated the serum haptoglobin levels in patients with pulmonary arterial hypertension (PAH) based on the hypothesis that haptoglobin levels would reflect subclinical hemolysis due to microangiopathy in pulmonary arterioles. This cross-sectional study included 3 groups of patients attending Hokkaido University Hospital: PAH, chronic thromboe...

Purpose of review: Antiphospholipid syndrome (APS) is a clinical disorder characterised by thrombosis and/or pregnancy morbidity in the persistence of antiphospholipid (aPL) antibodies that are pathogenic and have pro-coagulant activities. Thrombosis in APS tends to recur and require prophylaxis; however, the stereotypical treatment for APS patien...

Background: Thrombocytopenia is a non-criteria clinical manifestation of antiphospholipid syndrome (APS). However, it remains to be elucidated whether thrombocytopenia increases thrombotic risk in antiphospholipid antibody (aPL) carriers. Objectives: To investigate the impact of platelet count in terms of predicting thrombotic events in aPL carr...

The objective of this study is to identify the effects of statins and risk factors for thrombosis in patients with new onset of systemic lupus erythematosus (SLE) with or without antiphospholipid antibodies (aPL). Consecutive patients with SLE without history of thrombotic events were retrospectively enrolled from April 1997 to February 2014. The d...

Background In recurrent pregnancy loss (RPL), the pathogenesis of the majority of cases remains to be explained. Antiphospholipid, syndrome (APS) is one of the disorder responsible for causing RPL and its overwhelmed complement activation recognized as a major pathogenic mechanism. Autoantibodies against complement component 1q subcomponent (aC1q)...

Background Pulmonary arterial hypertension (PAH) is of great clinical significance as a life-threatening complication of connective tissue diseases (CTD). Pulmonary artery thrombotic microangiopathy (PATM) is an important pathophysiology of PAH. The concept of PATM refers to localized thrombotic microangiopathy to be defined histologically and shou...

Background Systemic lupus erythematosus (SLE) patients are prone to develop idiopathic osteonecrosis (ION) compared to other connective tissue disease patients or healthy subjects. ION has been shown to occur as a result of ischemia, however, the involvement of antiphospholipid antibodies (aPL) in its pathophysiology remains to be elucidated. In th...

Background and Aims Our group introduced a quantitative marker of antiphospholipid antibodies (aPL) ‘‘antiphospholipid score (aPL-S)’’, which well reflected the risk of developing thrombosis (Otomo K, et al. Arthritis Rheum 2012). Idiopathic osteonecrosis (ION) has been shown to occur as a result of ischemia, however, the involvement of aPL in its...

Background and aims Ras activation as well as MAP kinase (MAPK) phosphorylation is known in the synovial tissues from patients with rheumatoid arthritis (RA). RasGRP4 is a guanine nucleotide exchange factor for small GTPase Ras and is expressed predominantly in the mast cells, monocytes and neutrophils. We previously identified ectopic expression o...

Background and aims Anti-DNA/NR2 antibodies are a subset of anti DNA autoantibodies that cross-react with the extracellular domain of the GluN2A/GluN2B subunits of the N-methyl-d-aspartate receptor 2 (NR2), which induce apoptosis of hippocampus neurons and psychiatric disorder in mice and humans. Neuropsychiatric SLE (NPSLE) can develop after initi...

Pulmonary arterial hypertension (PAH) associated with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MTCD), in contrast to other types of PAH, may respond to immunosuppressive therapy. Most PAH cases with an immunosuppressant response were in the early stages of the disease (WHO functional class III or less). The present cas...

Objectives: To preliminarily evaluate the feasibility of maintenance therapy with reduced dose of intravenous abatacept (ABT) to 250mg/body/month after achieving remission or low disease activity (LDA). Patients and Methods: RA patients treated with ABT at 13 sites were enrolled in this prospective interventional pilot study during the period betwe...

Objectives To investigate the clinical impact of 1-year certolizumab pegol (CZP) therapy added to the first year of 2-year methotrexate (MTX) therapy, compared with 2-year therapy with MTX alone. Methods MTX-naïve patients with early rheumatoid arthritis (RA) with poor prognostic factors were eligible to enter Certolizumab-Optimal Prevention of jo...

Objectives: To evaluate the scoring of whole-body magnetic resonance imaging (WBMRI) for efficacy assessment in rheumatoid arthritis (RA) patients receiving biological disease-modifying anti-rheumatic drugs (bDMARDs). Methods: Thirty consecutive RA patients receiving bDMARDs were included in this retrospective study. Contrast WBMRI was performed be...

Small vessel vasculitis is a rare comorbidity of Takayasu arteritis (TA). This type of systemic vasculitis can be life-threatening. We present here a case involving small, medium-sized, and large vessels, and presumably microvessels. The patient, a 30-year-old woman, presented with saddle nose (Figure 1A), scleritis, and multiple skin ulcers in he...

Mean pulmonary arterial pressure of 21 to 24 mmHg, called borderline pulmonary arterial pressure (BoPAP), may represent a pre-pulmonary arterial hypertension (PAH) condition but has not so far been indicated for specific PAH therapy. Despite the recent progress in PAH-targeted therapy, the prognosis of patients with systemic sclerosis (SSc)-associa...

Objective: To verify predictive validity of simplified disease activity index (SDAI) remission for subsequent functional and structural outcomes in real-world clinical settings under a treat-to-target strategy (T2T). Methods: In this multicentre, prospective cohort study, T2T was implemented in rheumatoid arthritis patients with moderate-to-high...

Valosin containing protein (p97) is a chaperone implicated in a large number of biological processes including endoplasmic reticulum (ER)-associated protein degradation and autophagy. Silencing of p97 in rheumatoid arthritis (RA) synovial fibroblasts (RASFs) increased the amount of polyubiquitinated proteins, whereas silencing of its interaction pa...

Antiphospholipid antibodies (aPLs) can vary both immunologically and functionally, thus it is important to effectively and correctly identify their presence when diagnosing antiphospholipid syndrome. Furthermore, since many immunological/functional tests are necessary to measure aPLs, complete examinations are often not performed in many cases due...

Objectives: Pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc) has a poor prognosis compared to PAH associated with other connective tissue diseases (CTD). The objective of this study was to examine the difference in hemodynamic state between SSc-PAH and other CTD-PAH by performing cardiac magnetic resonance (CMR) imagi...

The involvement of complement activation in the pathophysiology of antiphospholipid syndrome (APS) was first reported in murine models of antiphospholipid antibody (aPL)-related pregnancy morbidities. We previously reported that complement activation is prevalent and may function as a source of procoagulant cell activation in the sera of APS patien...

Background Thrombocytopenia is a non-criteria manifestation of antiphospholipid syndrome (APS). Antiphospholipid antibodies (aPL) have been shown to activate platelet through multiple mechanisms. In patients with idiopathic/immune thrombocytopenia, aPL have been shown to increase the risk of thrombosis. Conversely, it remains unclear whether thromb...

Treatment of organ involvements accompanied by systemic autoimmune diseases is still challenging for clinicians, reminding the existence of unmet needs. Among them, lupus nephritis (LN), neuropsychiatric lupus, interstitial lung diseases (ILD) complicated with polymyositis/dermatomyositis (PM/DM) or systemic sclerosis (SSc) are the most severe cond...

Objective: To investigate the prevalence and significance of the autoantibodies against complement component 1 q subcomponent (C1q) in patients with APS. Methods: In all, 40 consecutive primary APS patients, 42 patients with non-SLE CTDs and 20 SLE patients negative for aPL were enrolled in this retrospective analysis. Refractory APS was defined...

Objective: The objective of this paper is to elucidate the not yet known plasma molecule candidates involved in the induction of tissue factor (TF) expression mediated by β2GPI-dependent anticardiolipin antibody (aCL/β2GPI) on monocytes. Methods: Human serum incubated with FLAG-β2GPI was applied for affinity chromatography with anti- FLAG antibo...

In patients with systemic lupus erythematosus (SLE), neuropsychiatric (NP) symptoms sometimes occur after administration of corticosteroids, making differential diagnosis between NPSLE and steroid-induced psychosis challenging for clinicians. The aim of this study was to clarify the characteristics of post-steroid NP disease (PSNP) in patients with...

Objective: Phosphatidylserine-dependent, also called aPS-PT, recognizes the phosphatidylserine-prothrombin complex, which is associated with APS. We have previously reported that aPS-PT induces tissue factor (TF) expression on monocytes through the p38 mitogen-activated protein kinase pathway. However, the cell surface interaction between prothrom...

The objective of this study was to directly compare the safety of tocilizumab (TCZ) and TNF inhibitors (TNFIs) in rheumatoid arthritis (RA) patients in clinical practice. This prospective cohort study included RA patients starting TCZ [TCZ group, n = 302, 224.68 patient-years (PY)] or TNFIs [TNFI group, n = 304, 231.01 PY] from 2008 to 2011 in the...

To conduct a national survey of systemic lupus erythematosus (SLE) patients treated with mycophenolate mofetil (MMF). Based on current information on the use of MMF, we aimed to evaluate its efficacy and safety for childhood-onset (c-) SLE. We evaluated 115 patients by questionnaire on MMF use for c-SLE in medical facilities specializing in pediatr...

Antiphospholipid antibodies (aPLs) are a group of heterogenous antibodies with immunological and functional variations that are detected in the sera of patients with antiphospholipid syndrome (APS). Detection of these antibodies in an efficient and accurate manner remains a significant issue. It requires numerous immunological and functional tests,...

A 56-year-old woman with systemic lupus erythematosus had bacteremia due to multidrug-resistant Pseudomonas aeruginosa (MDRP). She was initially treated with imipenem-cilastatin, tobramycin, and aztreonam; however, MDRP was still detected intermittently in her plasma. Multidrug-susceptibility tests demonstrated that MDRP was susceptible only to col...

To evaluate efficacy and safety of combination therapy using certolizumab pegol (CZP) and methotrexate (MTX) as first-line treatment for MTX-naive, early rheumatoid arthritis (RA) with poor prognostic factors, compared with MTX alone. MTX-naive, early RA patients with ≤12 months persistent disease, high anti-cyclic citrullinated peptide, and either...

Background Valosin containing protein (p97/VCP) is an ATPase implicated in the degradation of ubiquitin-labelled proteins through the proteasome. We recently described a resistance to apoptotic cell death induced by proteasome inhibition and a hypersensitivity to autophagy-associated cell death under conditions of severe endoplasmic reticulum (ER)...

Background Pulmonary arterial hypertension (PAH) is of great clinical significance in connective tissue diseases (CTD) because of its high mortality. In particular, prognosis of PAH associated with systemic sclerosis (PAH-SSc) is extremely poor compared with PAH associated with other CTD (PAH-non-SSc). The reason, however, remains to be elucidated....

Mycophenolate mofetil (MMF) is used for one of the standard induction/maintenance protocols for lupus nephritis (LN). However, MMF has not been approved for treating LN in any country, resulting in world-wide off-label use of this immunosuppressant. In order to clarify the real-world use of MMF as a treatment for LN in Japan, Japan College of Rheum...

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombosis and/or pregnancy complications. β2-glycoprotein I (β2GPI) complexed with phospholipid is recognized as a major target for autoantibodies in APS; however, less than half of the patients with clinical manifestations of APS possess autoantibodies against the complexe...

Pulmonary infections (PI) are leading causes of death in patients with connective tissue diseases (CTD). The PREVENT study (Pulmonary infections in patients receiving immunosuppressive treatment for CTD) assessed risk of PI in patients with active CTD in the contemporary era of advanced immunosuppressive therapy. In patients who started corticoster...

Background: Thromboses and pregnancy morbidities are major pathologies of antiphospholipid syndrome (APS). In general, rheumatologists or hematologists see APS thrombosis patients, and they often give advices for the treatments of APS-related pregnancy morbidities, such as measurements and interpretations of antiphospholipid antibodies(aPL). Obje...

Objective: Connective tissue disease-associated interstitial pneumonia (CTD-IP) significantly affects the mortality of patients with CTD. The purpose of the present study is to identify causes and risk factors for death during hospitalization for immunosuppressive treatment of CTD-IP. Methods: A multicenter, retrospective study was conducted tha...

To investigate changes in the risk for serious infections (SIs) over time in Japanese rheumatoid arthritis (RA) patients treated with tumor necrosis factor inhibitors (TNFIs). This prospective cohort study included Japanese RA patients who began treatment with a TNFI from 2005 to 2007 (2005 group, n = 716, 634.2 patient years [PY]) and from 2008 to...

Interstitial lung disease (ILD) in patients with polymyositis (PM) and dermatomyositis (DM) is often resistant to treatment and life threatening, being recognized as one of the severest complication in these autoimmune disorders. Patients with clinically amyopathic dermatomyositis (CADM) or those with anti-CADM140/MDA5 antibody are especially prone...

Objective Ras guanine nucleotide-releasing protein 4 (RasGRP-4) is a calcium-regulated guanine nucleotide exchange factor and diacylglycerol/phorbol ester receptor not normally expressed in fibroblasts. While RasGRP-4-null mice are resistant to arthritis induced by anti-glucose-6-phosphate isomerase autoantibodies, the relevance of these findings t...

β2-glycoprotein I (β2GPI) is an important autoantigen in patients with antiphospholipid syndrome (APS), an autoimmune disorder characterized by thrombosis and pregnancy morbidity. β2GPI is able to bind to anionic phospholipid via the lysine cluster and hydrophobic loop in the domain V Cys281-Cys288 region. It also binds annexin II, oxLDL, and apopt...