start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=1
article-no=
start-page=e000772
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220927
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Association of one-point glucocorticoid-free status with chronic damage and disease duration in systemic lupus erythematosus: a cross-sectional study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Objective It is still unclear how glucocorticoids (GCs) affect the long-term clinical course of patients with SLE. The objective of this study is to explore the factors associated with GC-free treatment status.
Methods Using data from the lupus registry of nationwide institutions, GC dose at registration was compared between short, middle and long disease durations of <5, 5–20 and ≥20 years, respectively. After excluding patients who never used GC, we evaluated the relationship between GC-free status and chronic damage using Systemic Lupus International Collaborating Clinics Damage Index.
Results GC doses at enrolment of the 1019 patients were as follows: GC-free in 101 (10%); 0
Conclusion Even in the patients with long disease duration, one-point GC-free treatment status might be related to no chronic damage accrual.
en-copyright=
kn-copyright=
en-aut-name=SadaKen-ei
en-aut-sei=Sada
en-aut-mei=Ken-ei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=KatayamaYu
en-aut-sei=Katayama
en-aut-mei=Yu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=AsanoYosuke
en-aut-sei=Asano
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=HayashiKeigo
en-aut-sei=Hayashi
en-aut-mei=Keigo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=MiyawakiYoshia
en-aut-sei=Miyawaki
en-aut-mei=Yoshia
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=OhashiKeiji
en-aut-sei=Ohashi
en-aut-mei=Keiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=KatsuyamaEri
en-aut-sei=Katsuyama
en-aut-mei=Eri
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=KatsuyamaTakayuki
en-aut-sei=Katsuyama
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=Takano-NarazakiMariko
en-aut-sei=Takano-Narazaki
en-aut-mei=Mariko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=MatsumotoYoshinori
en-aut-sei=Matsumoto
en-aut-mei=Yoshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=YoshimiRyusuke
en-aut-sei=Yoshimi
en-aut-mei=Ryusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=ShimojimaYasuhiro
en-aut-sei=Shimojima
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=OhnoShigeru
en-aut-sei=Ohno
en-aut-mei=Shigeru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=KajiyamaHiroshi
en-aut-sei=Kajiyama
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=IchinoseKunihiro
en-aut-sei=Ichinose
en-aut-mei=Kunihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=SatoShuzo
en-aut-sei=Sato
en-aut-mei=Shuzo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=FujiwaraMichio
en-aut-sei=Fujiwara
en-aut-mei=Michio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=YajimaNobuyuki
en-aut-sei=Yajima
en-aut-mei=Nobuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine
kn-affil=
affil-num=12
en-affil=Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine
kn-affil=
affil-num=13
en-affil=Center for Rheumatic Diseases, Yokohama City University Medical Center
kn-affil=
affil-num=14
en-affil=Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University
kn-affil=
affil-num=15
en-affil=Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences
kn-affil=
affil-num=16
en-affil=Department of Rheumatology, Fukushima Medical University School of Medicine
kn-affil=
affil-num=17
en-affil=Department of Rheumatology, Yokohama Rosai Hospital
kn-affil=
affil-num=18
en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine
kn-affil=
en-keyword=systemic lupus erythematosus
kn-keyword=systemic lupus erythematosus
en-keyword=glucocorticoids
kn-keyword=glucocorticoids
en-keyword=outcome assessment
kn-keyword=outcome assessment
en-keyword=health care
kn-keyword=health care
en-keyword=epidemiology
kn-keyword=epidemiology
END
start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=11
article-no=
start-page=e003134
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=202111
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=TIGIT/CD155 axis mediates resistance to immunotherapy in patients with melanoma with the inflamed tumor microenvironment
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background
Patients with cancer benefit from treatment with immune checkpoint inhibitors (ICIs), and those with an inflamed tumor microenvironment (TME) and/or high tumor mutation burden (TMB), particularly, tend to respond to ICIs; however, some patients fail, whereas others acquire resistance after initial response despite the inflamed TME and/or high TMB. We assessed the detailed biological mechanisms of resistance to ICIs such as programmed death 1 and/or cytotoxic T-lymphocyte-associated protein 4 blockade therapies using clinical samples.
Methods
We established four pairs of autologous tumor cell lines and tumor-infiltrating lymphocytes (TILs) from patients with melanoma treated with ICIs. These tumor cell lines and TILs were subjected to comprehensive analyses and in vitro functional assays. We assessed tumor volume and TILs in vivo mouse models to validate identified mechanism. Furthermore, we analyzed additional clinical samples from another large melanoma cohort.
Results
Two patients were super-responders, and the others acquired resistance: the first patient had a non-inflamed TME and acquired resistance due to the loss of the beta-2 microglobulin gene, and the other acquired resistance despite having inflamed TME and extremely high TMB which are reportedly predictive biomarkers. Tumor cell line and paired TIL analyses showed high CD155, TIGIT ligand, and TIGIT expression in the tumor cell line and tumor-infiltrating T cells, respectively. TIGIT blockade or CD155-deletion activated T cells in a functional assay using an autologous cell line and paired TILs from this patient. CD155 expression increased in surviving tumor cells after coculturing with TILs from a responder, which suppressed TIGIT+ T-cell activation. Consistently, TIGIT blockade or CD155-deletion could aid in overcoming resistance to ICIs in vivo mouse models. In clinical samples, CD155 was related to resistance to ICIs in patients with melanoma with an inflamed TME, including both primary and acquired resistance.
Conclusions
The TIGIT/CD155 axis mediates resistance to ICIs in patients with melanoma with an inflamed TME, promoting the development of TIGIT blockade therapies in such patients with cancer.
en-copyright=
kn-copyright=
en-aut-name=KawashimaShusuke
en-aut-sei=Kawashima
en-aut-mei=Shusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=InozumeTakashi
en-aut-sei=Inozume
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KawazuMasahito
en-aut-sei=Kawazu
en-aut-mei=Masahito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=UenoToshihide
en-aut-sei=Ueno
en-aut-mei=Toshihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=NagasakiJoji
en-aut-sei=Nagasaki
en-aut-mei=Joji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TanjiEtsuko
en-aut-sei=Tanji
en-aut-mei=Etsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=HonobeAkiko
en-aut-sei=Honobe
en-aut-mei=Akiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=OhnumaTakehiro
en-aut-sei=Ohnuma
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KawamuraTatsuyoshi
en-aut-sei=Kawamura
en-aut-mei=Tatsuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=UmedaYoshiyasu
en-aut-sei=Umeda
en-aut-mei=Yoshiyasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=NakamuraYasuhiro
en-aut-sei=Nakamura
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=KawasakiTomonori
en-aut-sei=Kawasaki
en-aut-mei=Tomonori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=KiniwaYukiko
en-aut-sei=Kiniwa
en-aut-mei=Yukiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=YamasakiOsamu
en-aut-sei=Yamasaki
en-aut-mei=Osamu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=FukushimaSatoshi
en-aut-sei=Fukushima
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=IkeharaYuzuru
en-aut-sei=Ikehara
en-aut-mei=Yuzuru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=ManoHiroyuki
en-aut-sei=Mano
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=SuzukiYutaka
en-aut-sei=Suzuki
en-aut-mei=Yutaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=NishikawaHiroyoshi
en-aut-sei=Nishikawa
en-aut-mei=Hiroyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=MatsueHiroyuki
en-aut-sei=Matsue
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
en-aut-name=TogashiYosuke
en-aut-sei=Togashi
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=
affil-num=1
en-affil=Research Institute, Chiba Cancer Center
kn-affil=
affil-num=2
en-affil=Research Institute, Chiba Cancer Center
kn-affil=
affil-num=3
en-affil=Research Institute, Chiba Cancer Center
kn-affil=
affil-num=4
en-affil=Division of Cellular Signaling, National Cancer Center Research Institute
kn-affil=
affil-num=5
en-affil=Research Institute, Chiba Cancer Center
kn-affil=
affil-num=6
en-affil=Research Institute, Chiba Cancer Center
kn-affil=
affil-num=7
en-affil=Department of Dermatology, University of Yamanashi
kn-affil=
affil-num=8
en-affil=Department of Dermatology, University of Yamanashi
kn-affil=
affil-num=9
en-affil=Department of Dermatology, University of Yamanashi
kn-affil=
affil-num=10
en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center
kn-affil=
affil-num=11
en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center
kn-affil=
affil-num=12
en-affil=Department of Pathology, Saitama Medical University International Medical Center
kn-affil=
affil-num=13
en-affil=Department of Dermatology, Shinshu University School of Medicine
kn-affil=
affil-num=14
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University
kn-affil=
affil-num=16
en-affil=Department of Molecular and Tumor Pathology, Chiba University Graduate School of Medicine
kn-affil=
affil-num=17
en-affil=Division of Cellular Signaling, National Cancer Center Research Institute
kn-affil=
affil-num=18
en-affil=Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo
kn-affil=
affil-num=19
en-affil=Division of Cancer Immunology, Research Institute/Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center
kn-affil=
affil-num=20
en-affil=Department of Dermatology, Chiba University Graduate School of Medicine
kn-affil=
affil-num=21
en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=10
article-no=
start-page=e244861
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=202110
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Idiopathic combined adrenocorticotropin and growth hormone deficiency mimicking chronic fatigue syndrome
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A 42-year-old man who had suffered from severe fatigue for 5 years was diagnosed as having chronic fatigue syndrome (CFS) and fibromyalgia. Endocrinological workup using combined anterior pituitary function tests showed that the patient had adrenocorticotropin hormone (ACTH) deficiency, with a normal pituitary MRI. Treatment with a physiologic dose of oral hydrocortisone replacement physically ameliorated his general fatigue. A secondary workup using a growth hormone-releasing peptide-2 test revealed that he also had growth hormone (GH) deficiency, and GH replacement therapy was started. His muscle pain and depression were improved by the therapy. Here, we present a rare case of combined deficiency of ACTH and GH in a middle-aged man with severe general fatigue. This case report aims to raise awareness of combined deficiency of ACTH and GH as a differential diagnosis of CFS and its mimics.
en-copyright=
kn-copyright=
en-aut-name=TokumasuKazuki
en-aut-sei=Tokumasu
en-aut-mei=Kazuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OchiKanako
en-aut-sei=Ochi
en-aut-mei=Kanako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=OtsukaFumio
en-aut-sei=Otsuka
en-aut-mei=Fumio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
affil-num=1
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Center for Education in Medicine and Health Sciences, Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END