THU0585 LYMPHADENOPATHY IN IGG4-RELATED DISEASE IS ASSOCIATED WITH DISEASE ACTIVITY AND EOSINOPHILIA
Authors: Satoshi Takanashi, Jun Kikuchi, Takanori Sasaki, Mitsuhiro Akiyama, Yuko Kaneko, Hidekata Yasuoka, Katsuya Suzuki, Kunio Sugahara, Tsutomu Takeuchi
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> IgG4-related disease (IgG4-RD) is an immune-mediated systemic disease characterized by the enlargement of multiple organs. IgG4-RD frequently involves the pancreas, lacrimal glands, salivary glands, bile duct, kidneys, lungs, and retroperitoneum, but can potentially affect any organs. Lymphadenopathy is often seen in patients with IgG4-RD along with other organ involvements, but the significance of the exist of lymphadenopathy in IgG4-RD is unclear. <h3>Objectives</h3> The aim of this study is to clarify the characteristics of patients with IgG4-RD who have lymphadenopathy. <h3>Methods</h3> We conducted cluster analysis with clinical data in consecutive 85 patients with untreated active IgG4-RD in our institute. We divided the patients into two groups who had lymphadenopathy or not (lymph group and non-lymph group), and compared clinical characteristics between the two groups. We counted the areas of swollen lymph nodes and performed correlation analysis with clinical characteristics. We also comprehensively screened serum protein concentrations in IgG4-RD patients (n=15) and healthy controls (n=5) by using high-throughput proteomic analysis, and differentially expressed proteins were extracted. We compared the concentrations of serum proteins which were extracted between lymph group and non-lymph group. <h3>Results</h3> Among 85 patients with IgG4-RD, 44 (52%) were male. Median age was 63 years old. Forty-seven (55%) patients were lymph group. Cluster analysis revealed that lymphadenopathy was in a cluster with serum IgG4, IgG4/IgG, IgG4-RD responder index (IgG4-RD RI), soluble interleukin-2 receptor (sIL-2R), eosinophilia, erythrocyte sedimentation rate (ESR), lung involvement, hemoglobin, albumin, C3 and C4. In lymph group, serum IgG4, IgG4/IgG, IgG4-RD RI, eosinophilia, sIL-2R and ESR were significantly higher than non-lymph group (Figure). Spearman's correlation analysis revealed that areas of the swollen lymph nodes were positively correlated with serum IgG4, IgG4/IgG, sIL-2R, eosinophilia. Proteomics analysis revealed that 68 proteins were significantly higher in IgG4-RD (p&lt;0.05). Among them, proteins related to adhesion of immune cells, fibrosis, formation of lymph node and eosinophil activation such as integrinα1β1, CCL18, CCL19 and eotaxin3 were higher in lymph group (p=0.03, p=0.03, p=0.06 and p=0.06, respectively) <h3>Conclusion</h3> Lymphadenopathy in IgG4-RD is associated with disease activity and eosinophilia. Proteomics analysis can provide some clues for elucidating the significance of lymphadenopathy in IgG4-RD. <h3>References</h3> [1] Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med2012;366:539–51. [2] Bookhout CE, Rollins-Raval MA. Immunoglobulin G4-Related Lymphadenopathy. Surg Pathol Clin. 2016;9:117-29. <h3>Disclosure of Interests</h3> Satoshi Takanashi: None declared, Jun Kikuchi: None declared, Takanori Sasaki: None declared, Mitsuhiro Akiyama: None declared, Yuko Kaneko Grant/research support from: Abbvie, Eisai, Speakers bureau: AbbVie, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Jansen, Kissei, Pfizer, Sanofi, Takeda, Tanabe-Mitsubishi, UCB, Hidekata Yasuoka: None declared, Katsuya Suzuki: None declared, Kunio Sugahara: None declared, Tsutomu Takeuchi Grant/research support from: Astellas Pharma Inc, Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., AbbVie GK, Asahikasei Pharma Corp., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Eisai Co., Ltd., AYUMI Pharmaceutical Corporation, Nipponkayaku Co. Ltd., Novartis Pharma K.K., Grant/research support from: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Grant/research support from: Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahi Kasei Pharma Corp., Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., Janssen Pharmaceutical K.K., Celltrion Inc., Nipponkayaku Co. Ltd., and UCB Japan, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Abbivie GK, Nipponkayaku Co.Ltd, Janssen Pharmaceutical K.K., Astellas Pharma Inc., Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Taisho Toyama Pharmaceutical Co. Ltd., GlaxoSmithKline K.K., UCB Japan Co. Ltd., Consultant for: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Asahi Kasei Medical K.K., AbbVie GK, Daiichi Sankyo Co., Ltd., Bristol Myers Squibb, and Nipponkayaku Co. Ltd., Speakers bureau: Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahi Kasei Pharma Corp., Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., Janssen Pharmaceutical K.K., Celltrion Inc., Nipponkayaku Co. Ltd., and UCB Japan, Speakers bureau: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Speakers bureau: AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Astellas Pharma Inc, Diaichi Sankyo Co. Ltd., Eisai Co. Ltd., Sanofi K.K., Teijin Pharma Ltd., Takeda Pharmaceutical Co. Ltd., Novartis Pharma K.K.