R. Wakiya

AB0527 S100 proteins are novel biomarkers for the efficacy of hcq treatment to skin lesion in systemic lupus erythematosus

Background Systemic lupus erythematosus(SLE) is deeply associated with not only acquired immunity but also innate immunity throughout toll like receptors(TLRs) signalling. Among many TLRs, TLR7 and TLR9 were reported to be closely associated with IFN-α production which contributed the pathogenesis of SLE. On the other hand, several reports demonstrated that S100A8 and S100A9 proteins which was known as one of damage-associated molecular patterns(DAMPs), were associated with disease activity of lupus nephritis. These proteins were also shown to reflect the treatment response by immunosuppressive therapy for SLE.1 2 However, there is no report about the effect of hydroxychloroquine(HCQ) on S100A8 and S100A9 proteins expression. Objectives To find a new biomarker of treatment with HCQ, we focused on expression of S100A8 and S100A9 proteins in SLE. Methods We enrolled all SLE patients treated with HCQ in the absence of additional immunosuppressive therapy more than 3 months in our institute from Jan 2016 to Dec 2017 Serum levels of S100A8 and S100A9 proteins were measured by ELISA(CircuLex ELISA Kit, MBL) at the screening, 3 months and 6 months after HCQ administration. Disease activity of SLE was measured using the SLENA-SLEDAI 2011 Cutaneous disease activity was evaluated by Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Immunological activity was examined by the levels of complement (C3, C4, CH50), anti-dsDNA anti-body and counting blood cell. Results 61 patients were enrolled in this study. HCQ was administered 48 cases with usual dose(based on ideal weight), 15 cases with low dose than usual dose (table 1).Abstract AB0527 – Table 1 HCQ dose Usual dose (n=46) Low dose (n=15) P Age, years, mean±SD 40±12 46±9 0.07 Female, no.(%) 43 (93) 13 (87) 0.40 Disease duration, years 13±10 11±8 0.61 skin lesion 40 (87) 14 (93) 0.48 renal lesion 19 (41) 0 (0) <0.001 SLEDAI score 3.9±2.2 2.7±1.8 0.06 anti-dsDNA, IU/ml 15±17 9.9±3.1 0.91 C3, mg/dl 79±24 87±26 0.32 C4, mg/dl 16.1±7.6 19.2±9.2 0.30 CH50, U/ml 33.6±9.6 37.3±7.4 0.30 CLASI activity 3.6±3.2 2.6±2.8 0.11 PrednisoneDose, mg/day 41 (89)5.6±3.1 15 (100)8.1±5.1 0.11 CLASI was improved by the treatment with HCQ independent of HCQ dose. However, the effect of HCQ on SLENA-SLEDAI and immunological biomarker was shown in the patients treated with usual dose HCQ, not shown in those treated with low dose HCQ. On the other hand, serum levels of S100A8 and S100A9 proteins were significantly elevated in SLE patients with renal lesion(p=0.02). These proteins were significantly decreased by the treatment with HCQ regardless of the HCQ dose(p<0.0001). The changes of serum S100A8 and S100A9 proteins during HCQ treatment(for 3 months) were significantly associated with changes of CLASI(figure 1).Abstract AB0527 – Figure 1 S100A8 and S100A9 proteins associated with CLASI score. Compared with SLE patients of 50% and less rate of change of CLASI activity, those of more than 50% rate of change of CLASI activity significantly decreased serum levels of S100A8 and S100A9 proteins after administration of HCQ. There were no SLE patients whose skin lesion got worse during HCQ treatment in this study. Conclusions HCQ reduced the expression of serum S100A8 and S100A9 proteins, which reflected SLE disease activity especially in skin lesion. The measurement of S100A8 and S100A9 proteins is novel predictive biomarker for the efficacy of HCQ treatment on skin lesion in SLE patients. References [1] Tyden H, et al. Pro-inflammatory S100 proteins are associated with glomerulonephritis and anti-dsDNA antibodies in systemic lupus erythematosus. Lupus2017;(26):139–149. [2] Tantivitayakul P, et al. Elevated expressions of myeloid-related proteins-8 and -14 are danger biomarkers for lupus nephritis. Lupus 2016;(25):38–45. Disclosure of Interest None declared

THU0209 Lymphocyte subsets in biopsy specimen are associated with spontaneous regression of lymphoproliferative disorders in rheumatoid arthritis patients treated with methotrexate

Background Patients with rheumatoid arthritis (RA) have a high risk for lymphoproliferative disorders (LPDs). An LPD in a patient treated with methotrexate (MTX) is known as MTX-associated LPD (MTX-LPD), which is classified among immunodeficiency-associated lymphoproliferative disorders (ID-LPD) as “other iatrogenic ID-LPD” in the 2008 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues (1). We previously reported that MTX is an independent risk factor for LPD onset in Japanese patients with RA (2). In MTX-LPD, MTX withdrawal can result in spontaneous regression of LPD. In addition, limited evidence indicates that Epstein–Barr virus infection is related to spontaneous regression of MTX-LPD. No biomarker has been identified that predicts spontaneous regression of MTX-LPD. Objectives To identify a biomarker that predicts spontaneous regression of MTX-LPD in RA patients. Methods We enrolled RA patients from Kagawa Prefecture, Japan, who developed MTX-LPD during the period from June 2010 through December 2016. RA was diagnosed in accordance with the American College of Rheumatology 1987 classification criteria and was treated with disease-modifying antirheumatic drugs, including MTX. The patients were divided into two groups: those followed-up after discontinuation of MTX alone (MTX withdrawal group) and those who received chemotherapy at 1 month or later after MTX discontinuation (chemotherapy group). The following variables were compared between groups: change in peripheral lymphocyte subsets after MTX discontinuation, serum soluble interleukin-2 receptor, and lymphocyte subsets and Epstein–Barr virus–encoded RNAs in a biopsy specimen from a lesion. Results We enrolled 43 MTX-LPD patients (29 in the withdrawal group and 14 in the chemotherapy group). From among these groups, we selected 32 patients for analysis of changes in peripheral lymphocyte subsets (23 in the withdrawal group and 9 in the chemotherapy group) and 22 for analysis of lymphocyte subsets in a lesion specimen (11 each in the withdrawal group and chemotherapy group). Peripheral lymphocyte counts were significantly higher after MTX discontinuation in the withdrawal group. Analysis of lymphocyte subsets from lesion specimens revealed significantly higher CD8-positive lymphocyte counts in the chemotherapy group than in the withdrawal group. Conclusions Lymphocyte count differed before and after MTX discontinuation, and a higher CD8-positive lymphocyte count in a lesion specimen was associated with spontaneous regression of MTX-LPD. These findings may help identify a predictive marker for MTX-LPD treatment and management. References Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press, Lyon, 2008. Association of higher methotrexate dose with lymphoproliferative disorders onset in rheumatoid arthritis patients. Kameda T, Dobashi H, Miyatake N, Inoo M, Onishi I, Kurata N, Mitsunaka H, Kawakami K, Fukumoto T, Susaki K, Izumikawa M, Nakashima S, Shimada H, Takeuchi Y, Haba R, Mano S, Onishi H, Imataki O, Matsunaga T. Arthritis Care Res (Hoboken). 2014 Sep;66(9):1302–9. Disclosure of Interest None declared

FRI0609 Usefulness of FDG-PET/CT imaging and serological biomarkers to predict relapse in IGG4-related disease

Background IgG4-RD shows relapses frequently. It is important to search to the factors to predict relapse. Recent research has shown the usefulness of FDG-PET/CT for IgG4-RD because it is more sensitive than conventional imaging to detect organ involvement of the disease. It has been suggested that FDG-PET/CT is also useful for monitoring therapeutic response of IgG4-RD. Objectives We investigate the usefulness of FDG-PET/CT imaging and serological biomarkers to predict relapse in IgG4-RD. Methods We analyzed 24 patients with IgG4-RD treated for more than 1 year between 2008 and 2016 in our facility. The diagnosis for IgG4-RD was based on comprehensive diagnostic criteria for IgG4-RD. All cases underwent FDG-PET/CT at least once, and laboratory data were collected from their medical records retrospectively. Levels of serum C-reactive protein (CRP), eosinophil/leukocyte ratio, serum IgG, IgG4, IgA, IgM, IgE, sIL2-R and serum compliment were investigated. Results The patients had a mean age of 67.9 years (range: 50–87 years). In the cases with high FDG uptake on FDG-PET/CT, they had a greater number of organ involvements, higher serum IgG and sIL-2R levels. Eight patients experienced relapses following treatment. Higher serum IgG predicted relapses of IgG4-RD. FDG-PET/CT findings at baseline were not associated with relapse. FDG-PET/CT was performed in 13 patients after initiation of treatment and 4 patients had a relapse. There were no significant reduction of abnormal FDG uptake in 6 patients, and 4 of 6 patients relapsed. Conclusions In this study, we examined the factors to predict relapse in IgG4-RD. Patients with higher serum IgG were regarded as a risk of relapse, but FDG-PET/CT findings at baseline were not associated with relapse. FDG-PET/CT reexamined after initiation of treatment is useful to predict relapse of IgG4-RD. References Umehara H, Okazaki K, Masaki Y, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol. 2012 Feb;22(1):21–30. Nakatani K. Utility of FDG PET/CT in IgG4-related systemic disease Clin Radiol. 2012 Apr;67(4):297–305. Zhang J, Chen H, Ma Y, et al. Characterizing IgG4-related disease with 18F-FDG PET/CT: a prospective cohort study. Eur J. Nucl Med Mol Imaging. 2014;41:1624–1634. Disclosure of Interest None declared

AB0294 Lymphocyte Recovery after Methotrexate Discontinuation Relate To Spontaneous Regression of Mtx-Lpd in Ra Patients

Background Rheumatoid arthritis (RA) patients have a high risk of onset of lymphoproliferative disorders (LPD). Especially, LPD develop in patients treated with methotrexate (MTX) is known as MTX-associated LPD (MTX-LPD). MTX-LPD is classified among the “immunodeficiency-associated lymphoproliferative disorders (ID-LPD)” as an “other iatrogenic ID-LPD” in the 2008 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (1). We previously reported that MTX is an independent risk factor for LPD onset in Japanese RA patients (2). Characteristic of MTX-LPD is that MTX withdrawal possibly results in spontaneous regression of the LPD. Furthermore, there are some reports that the Epstein-Barr virus (EBV) infection is related to spontaneous regression of MTX-LPD. However, enough evidence about the relation with EBV infection and spontaneous regression of MTX-LPD is not presented. In addition, biomarker predicting a spontaneous regression of MTX-LPD has not been clarified. Objectives We examined the clinical characteristics of MTX-LPD in Japanese RA patients and attempted to determine the predictive marker for spontaneous regression of MTX-LPD. Methods We enrolled 33 RA patients who developed MTX-LPD from Kagawa Prefecture, Japan between June 2010 and December 2015. Patients were diagnosed according to American College of Rheumatology 1987 classification criteria, and treated with disease modifying antirheumatic drugs (DMARDs) including MTX. We divided into patients who were followed-up after the discontinuation of MTX alone (MTX withdrawal group) and patients who were performed chemotherapy after one month or more of the MTX discontinuation (chemotherapy group). The following differences between the two groups were examined: 1) serum LDH; 2) serum CRP; 3) sIL-2 receptor; 4) lymphocyte counts before and after MTX discontinuation; 5) hemoglobin; 6) histological findings related to LPD; 7) EBV association; 8) number of LPD lesions and 9) outcome. Results There were 28 patients in the MTX withdrawal group and 5 patients in the chemotherapy group. Laboratory data such as LDH, CRP, sIL-2R, lymphocyte counts and hemoglobin showed no significant difference in two groups. Furthermore, there is no difference between two groups about EBV infection and number of LPD lesions. However, significant differences were found in the change ratio of lymphocyte between the two groups. Conclusions We revealed that the change of lymphocyte before and after the MTX discontinuation relate to spontaneous regression of the MTX-LPD. This data suggest that the recover of lymphocyte after the MTX discontinuation may become a predictive marker for MTX-LPD treatment strategy. References Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press, Lyon, 2008. Association of higher methotrexate dose with lymphoproliferative disorders onset in rheumatoid arthritis patients. Kameda T, Dobashi H, Miyatake N, Inoo M, Onishi I, Kurata N, Mitsunaka H, Kawakami K, Fukumoto T, Susaki K, Izumikawa M, Nakashima S, Shimada H, Takeuchi Y, Haba R, Mano S, Onishi H, Imataki O, Matsunaga T. Arthritis Care Res (Hoboken). 2014 Sep;66(9):1302–9. Disclosure of Interest None declared

AB0922 FDG-PET/CT Is A Valuable Tool for Relapsing Polychondritis

Background Relapsing polychondritis (RP) is a comparatively rare inflammatory disorder t in which recurrent episodes of inflammation occur in the external ear, nose, and joints. Although the pathogenesis of RP is unclear, it is believed to involve autoimmune mechanism such as autoantibody to type II collagen. Clinically, diagnosis in early stages of RP is difficult because of few typical physical findings. Furthermore, airway involvement is the most important complication of RP, and is associated with significant morbidity and mortality. Therefore it is important to diagnosis and treat RP in early stages. On the other hand, fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has been an established in a field of oncology. Recently, FDG-PET/CT is used as diagnostic tool for inflammatory disorder such as infection or collagen vascular disease. Objectives We investigate the features and the usefulness of FDG-PET/CT in the diagnosis of RP. Methods We enrolled the five RP patients (M/F: 1/4) who fulfilled the RP criteria by Damiani and Levine, and treated in our facility between 2005 and 2015. All patients had undergone FDG-PET/CT before treatment. Inflammatory lesion was evaluated by using the maximum standardized uptake value (SUV max). Furthermore, we performed follow-up FDG-PET/CT due to evaluate the efficacy of treatment for RP. Results FDG-PET/CT findings revealed abnormal FDG accumulation in the cartilages for all five patients. The lesions of abnormal FDG accumulation were tracheal/bronchial in 3 cases, auricular cartilage in 2 cases. The mean SUV max in tracheal/bronchial was 4.84 and in auricular cartilage was 2.53. All RP patients received glucocorticoid (GC) treatment. 3 patients were performed methylprednisolone-pulse therapy. All RP patients had well responce to initial GC treatment. However three patients were refractory for GC treatment. In these patients, one treated with methotrexate combined with GC and another 2 cases cyclophosphamide. The follow-up FDG-PET/CT was undergone in 2 patients. These findings revealed that FDG accumulation was significantly decreased or disappeared. Conclusions In RP patients, FDG-PET/CT is useful for the early diagnosis. Additionally, we suggest that FDG-PET/CT is valuable for monitoring response to treatment. References Jinlin Wang et al. Ann Nucl. Med. (2014)28:276–284 Yamashita H et al. Rheumatology 2014 Aug;53(8):1482–90 Disclosure of Interest None declared

THU0286 The Efficacy and The Long-Term Prognosis of Rituximab for Refractory Thrombotic Microangiopathy Associated with Connective Tissue Diseases

Background Recently, it has been described in many reports that B cell has important roles in connective tissue disease (CTD). Rituximab (RTX), anti-CD20 monoclonal antibody is widely known as effective for patients with several autoimmune hematological disorders including thrombotic microangiopathy (TMA) through not only B cell depletion but reducing antigen-presenting cell function, complement hyperactivation, release of inflammatory cytokines and abnormal auto-reactive T cell response through co-stimulatory signals.1) TMA is developed in CTD occasionally. CTD-TMA especially with normal activity of von Willebrand factor cleaving protease, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member-13 (ADAMTS-13) is often resistant for plasma exchange (PE) conducted for thrombotic thrombocytopenic purpura with ADAMTS-13 inhibitor and lack of ADAMTS-13 activity as a first-line treatment.2) It has been reported that the autoantibodies other than ADAMTS-13 inhibitor, complement hyperactivation, and excessive inflammatory cytokines production associated with refractory TMA.3) Objectives We investigate the efficacy and the long-term prognosis of RTX treatment for refractory TMA associated with CTD. Methods We enrolled 7 CTD-TMA patients (SLE; 3, SS; 2, MCTD; 1, DM; 1) with refractory to PE treatment between 2006 and 2015. We examined the ADAMTS-13 activity, its inhibitor and ultra-large von Willebrand factor multimers (UL-VWFMs) at TMA onset. RTX was given 375mg/m2 per a dose. We defined complete response (CR) as platelet counts >150×109/l for more than 3 consecutive days, with normal levels of serum LDH and an absence of TMA-related symptoms. We considered CR continued more than 30 days after RTX treatment as remission. In addition, we investigated as follow subjects; duration from initial RTX treatment to CR, duration of sustained CR, relapse and adverse events. Results No abnormality of ADAMTS-13 activity was observed 6 patients. The thrombocytopenia was improved immediately within 2–3 weeks after the initiation of RTX and hemolytic anemia and neuropsychiatric manifestations were improved following after the recovery of thrombocytopenia, respectively. 6 patients could achieve CR. They who achieved CR all have sustained long-term remission by only 1 or 2 doses of RTX administration and there was no relapse. RTX was partial response for 1 patient with insufficient recovery of thrombocytopenia but detectable serum haptoglobin and she was reported with controllable bacterial pneumonia. Conclusions We suggest that RTX treatment has efficacy with high response rate and long-term remission for the refractory CTD-TMA patients. Moreover, RTX treatment can be the first-line treatment for CTD-TMA. References Roberto Stasi. Rituximab in autoimmune hematologic disease: not just a matter of B cells. Semin Hematol. 2010; 47: 170–179. Tomomi Matsuyama, Masataka Kuwana, Masanori Matsumoto, et.al. Heterogeneous pathogenic processes of thrombotic microangiopathies in patients with connective tissue diseases. Thromb Haemost. 2009; 102: 371–378. Marina Noris, Federica Mescia, Giuseppe Remuzzi. STEC-HUS, atypical HUS and TTP are all diseases of complement activation. Nat. Rev. Nephrol. 2012; 8: 622–633. Disclosure of Interest None declared

AB0197 Evaluation of Serum IL-10 and IP-10 Levels Is Useful as Prognostic Biomarkers for Selection of IL-6R Antibody (TCZ) Prior To Tumor Necrosis Factor (TNF) Inhibitor in Rheumatoid Arthritis Treatment

Background Biomarkers of response to treatment in rheumatoid arthritis (RA) are sorely needed given the large inter-individual variability in efficacy of the available drugs. However, there is few reported to distinguish between responses to the different biologics (Bio) 1). Some authors think it will be difficult to obtain good predictive biomarkers for the efficacy of Bio before administration. Consequently, it is important that we identify the novel biomarker to predict the efficacy of these agents before the administration of Bio. Objectives To identify a serum biomarker for prediction of the response to Bio in patients with RA, we investigated whether serum cytokine level before treatment with Bio may represent useful prognostic biomarkers for TNF inhibitor (GLM) or IL-6R antibody (TCZ) treatment in bio-naïve RA. Methods To identify a serum biomarker for prediction of the response to Bio in patients with RA, we performed serum cytokines analysis in RA patients before and after Bio treatment with TCZ and GLM. At the first, we enrolled 10 responder and 10 poor-responder RA patients treated with Bio. 29 cytokines levels before treatment were measured using MILLIPLEX MAP Human Cytokine/Chemokine®. According to analysis of these 29 cytokines, IL-17, IL-6, IL-10 and IP-10 were eliminated as candidates for novel biomarker to predict the effectiveness of RA treatment. Then we enrolled 41 bio-naïve RA patients before administration of TCZ (n=27) or GLM (n=14). We measured these four serum cytokines before and after treatment with each Bio using ELISA. At baseline and 24 weeks after Bio-therapy with TCZ or GLM, we assessed DAS28 and measured serum levels of IL-17, IL-6, IL-10 and IP-10 using commercial ELISA kits. Responders and non-responders were defined as patients who had clinical remission (CR; DAS28 <2.6) and non-CR (DAS28 >2.6) at 24 week after administration of Bio. Wilcoxon two samples test was performed to compare cytokine levels. Results Mean age was 57.6±15.9, 70.6±14.7 years old and mean disease duration was 77.1±86.2, 114.0±142.6 months in TCZ and GLM patients, respectively. Disease activity of RA was 4.78±0.98 and 4.23±0.76 with DAS28 in TCZ and GLM patients, respectively. In CR group of TCZ (n=19), the serum IP-10 and IL-10 levels decreased compared with non-CR group by ELISA, significantly (P<0.05). As for RA patients treated with TCZ, IP-10 levels were significantly higher in responders. As for RA patients treated with GLM, responders showed a trend toward higher levels of baseline IL-10 compared to non- responders, while IP-10, IL-17 and IL-6 differences did not reach statistical significance. Conclusions In our study, the serum levels of IP-10 and IL-10 before Bio administration appeared to be associated with favorable responses to TCZ. Furthermore, these cytokines including IP-10 were not associated to response of GLM treatment. It is suggested that bio-naïve RA with low serum IP-10 levels might be treated with TCZ better than TNFi (GLM). References Gibbons LJ, Hyrich KL. Biologic therapy for rheumatoid arthritis: clinical efficacy and predictors of response. BioDrugs. 2009; 23(2): 111–24. Acknowledgement None. Disclosure of Interest None declared

THU0410 The Efficacy of Rituximab for Refractory Thrombotic Microangiopathy (TMA) Associated with Connective Tissue Diseases Regardless of Adamts-13 Activity Levels

Background Thrombotic microangiopathy (TMA) is characterized by microvascular thrombosis with thrombocytopenia, haemolytic anemia, and red blood cell fragmentation. TMA is often reported to develop under various clinical conditions such as malignant hypertension, stem cell transplantation, pregnancy, drug-induced, and connective tissue diseases (CTD). TMA is associated with deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member-13 (ADAMTS-13) induced by its inhibitor. Excessive production of ultra-large von Willebrand factor multimers (UL-VWFMs) also induced TMA. Plasma exchange (PE) is the standard treatment for TMA patients, and PE treatment can reduce mortality from 90% to less than 20% 1). However, some cases without the deficiency of ADAMTS-13 activity are resistant to PE treatment in TMA associated with CTD (CTD-TMA) 2). Recently, rituximab (RTX), anti-CD20 monoclonal antibody, is known as effective treatment for patients with refractory CTD-TMA. RTX is considered to affect on immune response by not only depleting B cells but modulating antigen-presenting cell function and release of inflammatory or immunomodulatory cytokines, and normalizing the abnormal auto-reactive T-cell response through co-stimulatory signals 3). Objectives We investigate the efficacy and safety of RTX treatment (two doses of RTX, 375 mg/m2 once per week) for CTD-TMA with refractory to PE treatment. Methods We enrolled six CTD-TMA patients with refractory to PE treatment. We examined the ADAMTS-13 activity, its inhibitor and UL-VWFMs at TMA onset.In addition, we investigated as follow subjects; efficacy of RTX treatment, duration from initial RTX treatment to complete remission (CR), duration of sustained CR, relapse and adverse events. Results Five patients were female and one was male with average age of 41.5 years. CTD included three systemic lupus erythematosus, two Sjögrens syndrome and one mixed connective tissue disease. No abnormality of ADAMTS-13 activity was observed in five patients. ADAMTS-13 inhibitor was also not detected these five patients. UL-VWFMs were detected with two patients with neither deficiency of ADAMTS-13 activity nor presence of its inhibitor. In all patients, the cytopenia such as anemia and thrombocytopenia was improved immediately after the initial RTX administration. In addition, five of six patients could achieve CR within two weeks, and they have sustained in CR for at least 24 weeks. After 24 weeks, one of five patients who achieved CR relapsed, but she could achieve 2nd-CR after RTX re-treatment.Refractory CTD-TMA was controlled with RTX treatment, and serious complications were not occurred. Conclusions We suggest that RTX treatment could be expected the efficacy and safety for the refractory CTD-TMA patients regardless of ADAMTS-13 activity levels. It is possible that RTX treatment might be first line treatment strategy for CTD-TMA patients. References Sadler JE. Von Willebrand factor, ADAMTS-13, and thrombotic thrombocytopenic purpura. Blood 2008; 112(1): 11-18. T Matsuyama. Heterogeneous pathogenic processes of thrombotic microangiopathies in patients with connective tissue diseases. Thromb Haemost 2009; 102: 371-378. Stasi R. Rituximab in autoimmune hematologic disease:not just a matter of B cells. Semin Hematol 2010; 47: 170-179. Disclosure of Interest None declared

FRI0056 Serum IL-10 and IP-10 Levels is an Important Predictor of Response to Tocilizumab in Bio-Naïve RA Patients

Background The efficacy of biologics is different on respective RA patients. Therefore we have to select the best one among all biologics for each RA patient. On the other hand, there is few report about good predictive biomarker for the efficacy of biologics before administration1,2. Consequently, it is important that we identify the novel biomarker to predict the efficacy of these agents before the administration of biologics. In our facility, we investigated the serum cytokines of responder or poor responder RA patients treated with Tocilizumab (TCZ). Thirty-three serum cytokine levels before TCZ administration were measured using MILLIPLEX MAP Human Cytokine/Chemokine®. In these serum cytokines, we extracted IL-17, IL-6, IL-10, IL-13 and IP-10 as novel biomarker to predict the effectiveness of TCZ. Objectives We focused on serum cytokines such as IL-17, IL-6, IL-10, IL-13 and IP-10 in Bio-naïve RA patients treated with TCZ, and reveal characteristics of biomarkers to predict the efficacy of this biologics. Methods We enrolled 27 bio-naïve RA patients before TCZ administration. We measured these five serum cytokines using ELISA. We divided these 27 bio-naïve RA patients into clinical remission (CR; DAS28 ESR <2.6) and non-CR (DAS28 ESR >2.6) group at week 24, and compared these cytokines in two groups. Results Mean age was 57.6±15.9 years old and mean disease duration was 77.1±86.2 months. Disease activity of RA before TCZ administration was 4.48±0.87 and 5.01±1.26 with DAS28 ESR in CR (n=19) and non-CR (n=8), respectively. There was no difference in patient profile between two groups. In CR group, the serum IL-10 and IP-10 levels increased compared with non-CR group by ELISA, significantly (P<0.05). There is no difference between two groups in the levels of IL-17, IL-6 and IL-13. Conclusions In our study, the serum levels of IL-10 and IP-10 before TCZ administration were different between CR and non-CR at week 24 with Bio-naïve RA patients. We suggest that serum IL-10 and IP-10 levels could predict the efficacy of TCZ on bio-naïve RA patients. References Gibbons LJ, Hyrich KL. Biologic therapy for rheumatoid arthritis: clinical efficacy and predictors of response. BioDrugs. 2009; 23(2): 111-24. Chen DY, Chen YM, Chen HH, Hsieh CW, Lin CC, Lan JL. Increasing levels of circulating Th17 cells and interleukin-17 in rheumatoid arthritis patients with an inadequate response to anti-TNF-α therapy. Arthritis Res Ther. 2011 Jul 30; 13 (4): R126. Disclosure of Interest None declared

SAT0535 Usefulness of FDG-PET Imaging and Serological Biomarkers in Lymphadenopathy of IgG4-Related Disease

Background IgG4-related disease (IgG4-RD) is not rare and clinically important disease. It is very difficult to confirm the diagnosis because IgG4 positive lymphocyte infiltrates various organs such as pancreas, salivary glands, retroperitoneum, and kidney. Especially, lymphadenopathy is a common symptom in IgG4-RD patients. In addition, some cases have only lymphadenopathy in IgG4-RD. On the other hand, we presented that FDG-PET/CT was useful to improve a diagnosis rate in our facility. However, it is difficult for the rheumatologist to distinguish lymphadenopathy from other benign disorders such as viral infection and sarcoidosis using FDG-PET/CT only. Objectives We examine the tool to distinguish for the case of lymphadenopathy suspected IgG4-RD. Methods We enrolled 26 cases with suspected IgG4-RD in our facility between Jan. 2008 and Dec. 2014. Furthermore, we classified these 26 cases into IgG4-RD (IgG4- RD group) and other benign disorders (non IgG4-RD group). The diagnosis for IgG4-RD was based on comprehensive diagnostic criteria for IgG4-RD. We investigated the serum IgG4 levels, sIL2-R levels and maximum standardized uptake value (SUVmax) of abnormal lymph node accumulation by FDG-PET/CT. We retrospectively examined the relations of these three values. Results Lymphadenopathy were detected in 19 of 26 cases (IgG4-RD definite: 8, IgG4-RD possible: 5, IgG4-RD probable: 1, infectious disease: 2, SLE: 1, EGPA: 1, Castleman disease: 1). In IgG4-RD group, serum IgG4 level elevated and serum sIL-2R levels decreased in comparison with non IgG4-RD group respectively. There is no difference between two groups in SUVmax. Conclusions In our study, we examined the differentiation of lymphadenopathy. We proved that it was difficult to distinguish IgG4-RD from other benign disorders for lymphadenopathy only by FDG-PET/CT. We suggested that combination of serum IgG4 and sIL-2R levels is useful for diagnosis of IgG4-RD with lymphadenopathy. References Umehara H, Okazaki K, Masaki Y, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol. 2012 Feb;22(1):21-30. Nakatani K. Utility of FDG PET/CT in IgG4-related systemic disease Clin Radiol. 2012 Apr;67(4):297-305. Disclosure of Interest None declared