Distinct clinical outcomes based on multiple serum cytokine and chemokine profiles rather than autoantibody profiles and ultrasound findings in rheumatoid arthritis: a prospective ultrasound cohort study
Objectives To evaluate the potential of clinical factors, ultrasound findings, serum autoantibodies, and serum cytokine and chemokine profiles as predictors of clinical outcomes in rheumatoid arthritis (RA).Patients and methods We included 200 patients with RA treated with biological and targeted sy...
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2025-01-01
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| author | Yukitaka Ueki Tom W J Huizinga René E M Toes Shoichi Fukui Tomoki Origuchi Takahiro Maeda Atsushi Kawakami Tomohiro Koga Naoki Matsuoka Toshihiko Hidaka Naoki Iwamoto Mami Tamai Shin-ya Kawashiri Akitomo Okada Ayako Nishino Tamami Yoshitama Takahisa Suzuki Toshimasa Shimizu Shimpei Morimoto Tomomi Tsuru Karin A J van Schie Masahiro Ayano Remi Sumiyoshi Yushiro Endo Tohru Michitsuji Kaori Furukawa Masataka Umeda Nobutaka Eiraku Hiroaki Hamada |
| author_facet | Yukitaka Ueki Tom W J Huizinga René E M Toes Shoichi Fukui Tomoki Origuchi Takahiro Maeda Atsushi Kawakami Tomohiro Koga Naoki Matsuoka Toshihiko Hidaka Naoki Iwamoto Mami Tamai Shin-ya Kawashiri Akitomo Okada Ayako Nishino Tamami Yoshitama Takahisa Suzuki Toshimasa Shimizu Shimpei Morimoto Tomomi Tsuru Karin A J van Schie Masahiro Ayano Remi Sumiyoshi Yushiro Endo Tohru Michitsuji Kaori Furukawa Masataka Umeda Nobutaka Eiraku Hiroaki Hamada |
| author_sort | Yukitaka Ueki |
| collection | DOAJ |
| description | Objectives To evaluate the potential of clinical factors, ultrasound findings, serum autoantibodies, and serum cytokine and chemokine profiles as predictors of clinical outcomes in rheumatoid arthritis (RA).Patients and methods We included 200 patients with RA treated with biological and targeted synthetic disease-modifying antirheumatic drugs in a prospective multicentre ultrasound cohort study. Their serum levels of multiple cytokines and chemokines, rheumatoid factors, and serum autoantibodies (anti-cyclic citrullinated peptide-2 (anti-CCP2) and anti-carbamylated protein antibodies) were measured at baseline, 3 months and 12 months.Results Dimensionality reduction using 38 cytokines and chemokines demonstrated four distinct clusters that differed significantly regarding the frequencies of remission defined by clinical composite measures and ultrasound evaluations. Prominent differences in IL-1β, IL-5, IL-7, IL-10, IFNγ, GRO, IP-10, MCP-1 and MIP-1β characterised the between-cluster differences. Two distinct groups made of four clusters showed a significant difference in IgM-anti-CCP2 positivity. The least absolute shrinkage and selection operator regression of 38 cytokines and chemokines for Clinical Disease Activity Index (CDAI) remission at 12 months resulted in the selection of MIP-1β. Logistic regression using baseline levels of anti-citrullinated protein antibody, IgM-anti-CCP2 positivity, the CDAI, the total power Doppler score, the cluster by cytokines and chemokines, MIP-1β, methotrexate dose and mechanisms of action revealed that cluster by cytokines and chemokines was the sole significant factor for CDAI remission at 12 months.Conclusions Specific patterns of cytokines and chemokines—no other clinical factors and autoantibody profiles—were important to distinguish patients with RA achieving remission at 12 months.Trial registration number UMIN000012524. |
| format | Article |
| id | doaj-art-7b940481a86e457a8b1afaafe7a6e344 |
| institution | Kabale University |
| issn | 2056-5933 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMJ Publishing Group |
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| spelling | doaj-art-7b940481a86e457a8b1afaafe7a6e3442025-01-27T09:25:09ZengBMJ Publishing GroupRMD Open2056-59332025-01-0111110.1136/rmdopen-2024-005163Distinct clinical outcomes based on multiple serum cytokine and chemokine profiles rather than autoantibody profiles and ultrasound findings in rheumatoid arthritis: a prospective ultrasound cohort studyYukitaka Ueki0Tom W J Huizinga1René E M Toes2Shoichi Fukui3Tomoki Origuchi4Takahiro Maeda5Atsushi Kawakami6Tomohiro Koga7Naoki Matsuoka8Toshihiko Hidaka9Naoki Iwamoto10Mami Tamai11Shin-ya Kawashiri12Akitomo Okada13Ayako Nishino14Tamami Yoshitama15Takahisa Suzuki16Toshimasa Shimizu17Shimpei Morimoto18Tomomi Tsuru19Karin A J van Schie20Masahiro Ayano21Remi Sumiyoshi22Yushiro Endo23Tohru Michitsuji24Kaori Furukawa25Masataka Umeda26Nobutaka Eiraku27Hiroaki Hamada28Kyushu Multicenter Rheumatoid Arthritis Ultrasound Prospective Observational Cohort Study Group, Nagasaki, Japan1 Department of Rheumatology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands1 Department of Rheumatology, Leiden University Medical Center, Leiden, Zuid-Holland, The NetherlandsDepartment of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanNagasaki University, Department of Immunology and Rheumatology, Unit of Advanced Preventive Medical Sciences, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of General Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan2 Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanNagasaki University, Department of Immunology and Rheumatology, Unit of Advanced Preventive Medical Sciences, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan6Nagasaki Medical Hospital of Rheumatology, Nagasaki, Japan3 Institute of Rheumatology, Zenjinkai Shimin-no-Mori Hospital, Miyazaki, JapanDepartment of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan4 Department of Immunology and Rheumatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan4 Department of Immunology and Rheumatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan5Department of Rheumatology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, JapanUnit of Translational Medicine, Department of Immunology and Rheumatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, JapanYoshitama rheumatology clinic, Kirishima, Japan1 Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanNagasaki University, Department of Immunology and Rheumatology, Unit of Advanced Preventive Medical Sciences, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Nagasaki, Japan4 PS Clinic, Fukuoka, JapanRheumatology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Medicine and Biosystemic Science, Kyushu University, Fukuoka, JapanDepartment of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanNagasaki University, Department of Immunology and Rheumatology, Unit of Advanced Preventive Medical Sciences, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanKyushu Multicenter Rheumatoid Arthritis Ultrasound Prospective Observational Cohort Study Group, Nagasaki, JapanKyushu Multicenter Rheumatoid Arthritis Ultrasound Prospective Observational Cohort Study Group, Nagasaki, JapanObjectives To evaluate the potential of clinical factors, ultrasound findings, serum autoantibodies, and serum cytokine and chemokine profiles as predictors of clinical outcomes in rheumatoid arthritis (RA).Patients and methods We included 200 patients with RA treated with biological and targeted synthetic disease-modifying antirheumatic drugs in a prospective multicentre ultrasound cohort study. Their serum levels of multiple cytokines and chemokines, rheumatoid factors, and serum autoantibodies (anti-cyclic citrullinated peptide-2 (anti-CCP2) and anti-carbamylated protein antibodies) were measured at baseline, 3 months and 12 months.Results Dimensionality reduction using 38 cytokines and chemokines demonstrated four distinct clusters that differed significantly regarding the frequencies of remission defined by clinical composite measures and ultrasound evaluations. Prominent differences in IL-1β, IL-5, IL-7, IL-10, IFNγ, GRO, IP-10, MCP-1 and MIP-1β characterised the between-cluster differences. Two distinct groups made of four clusters showed a significant difference in IgM-anti-CCP2 positivity. The least absolute shrinkage and selection operator regression of 38 cytokines and chemokines for Clinical Disease Activity Index (CDAI) remission at 12 months resulted in the selection of MIP-1β. Logistic regression using baseline levels of anti-citrullinated protein antibody, IgM-anti-CCP2 positivity, the CDAI, the total power Doppler score, the cluster by cytokines and chemokines, MIP-1β, methotrexate dose and mechanisms of action revealed that cluster by cytokines and chemokines was the sole significant factor for CDAI remission at 12 months.Conclusions Specific patterns of cytokines and chemokines—no other clinical factors and autoantibody profiles—were important to distinguish patients with RA achieving remission at 12 months.Trial registration number UMIN000012524.https://rmdopen.bmj.com/content/11/1/e005163.full |
| spellingShingle | Yukitaka Ueki Tom W J Huizinga René E M Toes Shoichi Fukui Tomoki Origuchi Takahiro Maeda Atsushi Kawakami Tomohiro Koga Naoki Matsuoka Toshihiko Hidaka Naoki Iwamoto Mami Tamai Shin-ya Kawashiri Akitomo Okada Ayako Nishino Tamami Yoshitama Takahisa Suzuki Toshimasa Shimizu Shimpei Morimoto Tomomi Tsuru Karin A J van Schie Masahiro Ayano Remi Sumiyoshi Yushiro Endo Tohru Michitsuji Kaori Furukawa Masataka Umeda Nobutaka Eiraku Hiroaki Hamada Distinct clinical outcomes based on multiple serum cytokine and chemokine profiles rather than autoantibody profiles and ultrasound findings in rheumatoid arthritis: a prospective ultrasound cohort study RMD Open |
| title | Distinct clinical outcomes based on multiple serum cytokine and chemokine profiles rather than autoantibody profiles and ultrasound findings in rheumatoid arthritis: a prospective ultrasound cohort study |
| title_full | Distinct clinical outcomes based on multiple serum cytokine and chemokine profiles rather than autoantibody profiles and ultrasound findings in rheumatoid arthritis: a prospective ultrasound cohort study |
| title_fullStr | Distinct clinical outcomes based on multiple serum cytokine and chemokine profiles rather than autoantibody profiles and ultrasound findings in rheumatoid arthritis: a prospective ultrasound cohort study |
| title_full_unstemmed | Distinct clinical outcomes based on multiple serum cytokine and chemokine profiles rather than autoantibody profiles and ultrasound findings in rheumatoid arthritis: a prospective ultrasound cohort study |
| title_short | Distinct clinical outcomes based on multiple serum cytokine and chemokine profiles rather than autoantibody profiles and ultrasound findings in rheumatoid arthritis: a prospective ultrasound cohort study |
| title_sort | distinct clinical outcomes based on multiple serum cytokine and chemokine profiles rather than autoantibody profiles and ultrasound findings in rheumatoid arthritis a prospective ultrasound cohort study |
| url | https://rmdopen.bmj.com/content/11/1/e005163.full |
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