1.Monitoring checkpoint inhibitors: predictive biomarkers in immunotherapy.
Min ZHANG ; Jingwen YANG ; Wenjing HUA ; Zhong LI ; Zenghui XU ; Qijun QIAN
Frontiers of Medicine 2019;13(1):32-44
Immunotherapy has become the fourth cancer therapy after surgery, chemotherapy, and radiotherapy. In particular, immune checkpoint inhibitors are proved to be unprecedentedly in increasing the overall survival rates of patients with refractory cancers, such as advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. However, inhibitor therapies are only effective in a small proportion of patients with problems, such as side effects and high costs. Therefore, doctors urgently need reliable predictive biomarkers for checkpoint inhibitor therapies to choose the optimal therapies. Here, we review the biomarkers that can serve as potential predictors of the outcomes of immune checkpoint inhibitor treatment, including tumor-specific profiles and tumor microenvironment evaluation and other factors.
Autoantibodies
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blood
;
immunology
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Biomarkers, Tumor
;
blood
;
immunology
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Humans
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Immunotherapy
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Neoplasms
;
blood
;
therapy
;
Tumor Microenvironment
2.Clinical Characteristics of Autoimmune Disease with Dual Seropositive Antibodies of Leucine-rich Glioma Inactivated 1 and Contactin-associated Protein 2.
Li Ling DONG ; Hong Zhi GUAN ; Yan HUANG ; Hong Lin HAO ; Jing Wen NIU ; Qing LIU ; Qiang LU ; Dan XU ; Jun Yi ZHANG ; Li Xin ZHOU ; Li Ri JIN ; Hai Tao REN ; Yi Cheng ZHU ; Bin PENG ; Li Ying CUI ; Xiang Qin ZHOU
Acta Academiae Medicinae Sinicae 2019;41(3):344-350
Objective To explore the clinical characteristics of autoimmune disease with dual seropositive antibodies of leucine-rich glioma inactivated 1(LGI1)and contactin-associated protein 2(Caspr2).Methods The clinical data of seven patients with dual seropositive LGI1 and Caspr2 antibodies who were admitted to the Neurology Department of Peking Union Medical College Hospital from July 2014 to December 2017 were retrospectively analyzed.Results Central,peripheral and autonomic nervous systems were all involved in the seven cases;100%(7/7)presented with insomnia,myokymia,neuropahic pain and hyperhydrosis;71%(5/7)showed memory decline or psychiatric and behavioral symptoms;57%(4/7)had urinary hesitation or constipation;and 43%(3/7)had seizure.Electromyography showed 100%(6/6) of the patients had prolonged afterdischarges following normal M waves and/or abnormal spontaneous firing.Electroencephalography revealed slow waves or basic rhythm slowing in 71%(5/7)of patients.Electrocardiography showed sinus tachycardia,axis deviation,and prolonged QT intervals in 71%(5/7)of patients.One patient died from arrhythmia before immunotherapy.One died from pulmonary infection after immunotherapy.Improvement with immunotherapy was documented in the other five cases.No relapse was noted during the 1-2-year follow-up.Conclusions Autoimmune disease with dual seropositive antibodies of LGI1 and Caspr2 can diffusely affect the central,peripheral,and autonomic nervous systems.The possibility of this disease should be considered in patients with acute and subacute onset of neuropsychiatric symptoms,especially in patients with accompanying insomnia,myokymia,and hyperhydrosis.
Autoantibodies
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blood
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Autoimmune Diseases
;
immunology
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Humans
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Membrane Proteins
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immunology
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Nerve Tissue Proteins
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immunology
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Proteins
;
immunology
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Retrospective Studies
3.Clinical characteristic of 74 cases of malignant tumor in rheumatoid arthritis.
Yu Hua WANG ; Guo Hua ZHANG ; Ling Ling ZHANG ; Jun Li LUO ; Lan GAO ; Mian Song ZHAO
Journal of Peking University(Health Sciences) 2018;50(6):986-990
OBJECTIVE:
To investigate the clinical characteristics of rheumatoid arthritis (RA) patients with malignant tumor.
METHODS:
Retrospective summary was made of 1 562 in patients of RA from January 2011 to June 2017. In the study, 74 RA patients with malignant tumor were reviewed and analyzed, and the general conditions, tumor types, RA and tumor onset sequence, and the medication situation were analyzed.
RESULTS:
The incidence of malignant tumor in the patients with rheumatoid arthritis in our center was 4.16%. The 74 patients were complicated with malignant tumor, of whom 53 were female, and 21 male. The age of RA at presentation was (52.6±17.8) years. The average disease duration of malignant tumor was (63.4 ± 12.7) years. The onset time of rheumatoid arthritis was earlier than that of malignant tumors in 51 cases (51/74), with an average of (17.2±14.2) years between 2 and 60 years. The incidence of malignant tumor was earlier than that of rheumatoid arthritis in 16 cases (16/74), with an average of (6.2±5.9) years between 1 and 21 years, of which 10 cases were sex hormone related tumors. Seven cases (7/74) were diagnosed with RA at the same time, and the time interval between the two diseases was within 1 year. All the patients were over 60 years old with digestive tract tumors. All the 7 patients showed polyarthritis, significantly increased erythrocyte sedimentation rate and C-reactive protein, including 4 rheumatoid factor positive cases and 2 anti-CCP antibody positive cases. The effect of non-steroidal anti-inflammatory drugs and traditional drugs to improve the condition of the disease was poor in the 7 patients, and the condition was relieved after using low-dose glucocorticoids. Gastrointestinal tumors, breast and reproductive system tumors were the most common, followed by respiratory, urological and blood system tumors.
CONCLUSION
The risk in patients of rheumatoid arthritis complicated with malignant tumor is higher than that of the general population. A variety of factors play an important role in cancer risk of RA, including disease activity, some estrogen metabolites, the use of drugs and so on. Therefore, all RA patients should be screened for malignant tumor during diagnosis, and malignant tumor surveillance is mandatory for all rheumatoid arthritis patients after diagnosis.
Adult
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Aged
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Arthritis, Rheumatoid/complications*
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Autoantibodies
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C-Reactive Protein/analysis*
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Female
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Humans
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Male
;
Middle Aged
;
Neoplasms/immunology*
;
Peptides, Cyclic
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Retrospective Studies
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Rheumatoid Factor/blood*
4.Thyroxine (T4) Autoantibody Interference of Free T4 Concentration Measurement in a Patient With Hashimoto's Thyroiditis.
Mi Na LEE ; Soo Youn LEE ; Kyu Yeon HUR ; Hyung Doo PARK
Annals of Laboratory Medicine 2017;37(2):169-171
No abstract available.
Adult
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Autoantibodies/*immunology
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Female
;
Hashimoto Disease/*diagnosis
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Humans
;
Luminescent Measurements
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Radioimmunoassay
;
Republic of Korea
;
Thyroid Function Tests
;
Thyroxine/*blood/immunology
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Triiodothyronine/blood
5.Bone Scintigraphy in the Diagnosis of Rheumatoid Arthritis: Is There Additional Value of Bone Scintigraphy with Blood Pool Phase over Conventional Bone Scintigraphy?.
Ji Young KIM ; Yun Young CHOI ; Chan Woo KIM ; Yoon Kyoung SUNG ; Dae Hyun YOO
Journal of Korean Medical Science 2016;31(4):502-509
We aimed to investigate the value of bone scintigraphy with additional blood pool phase (BSBP), compared with conventional bone scintigraphy (CBS), in the assessment of rheumatoid arthritis (RA). A total of 242 patients (43 males, 199 females; 14-78 years) with arthralgia, and underwent BSBP were retrospectively analyzed. On the first physical examination, active arthritis was found in 128 of the 242 patients. Clinical diagnosis was made by a rheumatologist on the basis of the 1987 American College of Rheumatology (ACR) criteria, which are considered to be the gold standard. The diagnostic performances and prognostic value of BSBP and CBS were analyzed in the total patients with arthralgia and in the patients with arthritis. The sensitivity of BSBP (84.2%, 80/95) were significantly higher than that of CBS (74.8%, 72/95) in the patients with arthralgia (P = 0.039). When BSBP was interpreted with the results of elevated/positive anti-CCP antibody, its accuracy over CBS also became significantly higher (86.0%, 208/242 vs. 83.1%, 201/242 respectively, P = 0.021). The diagnostic odds ratio of BSBP positivity was higher than CBS positivity in the patients with arthralgia (26.0, 12.9-52.4 vs. 21.1, 10.8-41.3) and with arthritis (12.0, 4.9-29.4 vs. 10.0, 4.2-23.4). Both BSBP and CBS appear to provide acceptable accuracy and comparable diagnostic performance for diagnosis of RA. However, in the patients with arthralgia, BSBP was found to be more sensitive than CBS and more accurate when interpreted with the result of anti-CCP antibody. This could help physicians diagnose RA in daily clinical practice.
Adolescent
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Adult
;
Aged
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Arthralgia/complications
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Arthritis, Rheumatoid/complications/*diagnosis
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Autoantibodies/blood
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Bone and Bones/diagnostic imaging
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Female
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*Gated Blood-Pool Imaging
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Humans
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Male
;
Middle Aged
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Odds Ratio
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Peptides, Cyclic/immunology
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Positron-Emission Tomography
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Prognosis
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Retrospective Studies
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Sensitivity and Specificity
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Technetium/chemistry
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*Tomography, X-Ray Computed
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Young Adult
6.Non-Paraneoplastic Autoimmune Retinopathy: The First Case Report in Korea.
Eun Young CHOI ; Min KIM ; Grazyna ADAMUS ; Hyoung Jun KOH ; Sung Chul LEE
Yonsei Medical Journal 2016;57(2):527-531
Autoimmune retinopathy (AIR) is an immune-mediated retinopathy, resulting from an immunologic process caused by the aberrant recognition of retinal antigens as autoantigens. The diagnosis of AIR involves the detection of antiretinal antibodies with concurrent clinical and electrophysiological evidence of retinopathy. A 40-year-old patient presented with progressive loss of bilateral vision over several months. A fundus examination was unremarkable. Spectral domain optical coherence tomography revealed a blurred photoreceptor ellipsoid zone at the subfoveal region in both eyes with more prominent disruption in the left eye. Full-field electroretinography (ERG) showed relatively normal rod and cone responses in the right eye, and decreased photopic bwaves with minimal attenuation of a-waves in the left eye. Multifocal ERG demonstrated slightly reduced amplitude of the inner segment ring in the right eye and decreased amplitudes and delayed latencies of all modalities in the left eye. The patient was suspected to have AIR and it was supported by positive Western blots for 23-kDa protein, enolase (46-kDa), aldolase (40-kDa), 62-kDa and 78-kDa proteins and by immunohistochemical staining of human retinal bipolar and ganglion cells. Despite the immunosuppressive treatment, the destruction of the retinal photoreceptors progressed, and immunosuppressive interventions produced very little visual improvement. We report on what is, to the best of our knowledge, the very first case of serologically confirmed nonparaneoplastic AIR in Korea.
Autoantibodies/*blood/immunology
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Autoantigens
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Autoimmune Diseases/*immunology
;
Electroretinography
;
Humans
;
Immunologic Factors
;
Paraneoplastic Syndromes/*immunology
;
Paraneoplastic Syndromes, Ocular
;
Phosphopyruvate Hydratase
;
Recoverin
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Republic of Korea
;
Retina/*immunology
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Retinal Diseases/*immunology
;
Tomography, Optical Coherence
7.The Significance of Ectopic Germinal Centers in the Minor Salivary Gland of Patients with Sjogren's Syndrome.
Kyung Eun LEE ; Ji Hyoun KANG ; Yi Rang YIM ; Ji Eun KIM ; Jeong Won LEE ; Lihui WEN ; Dong Jin PARK ; Tae Jong KIM ; Yong Wook PARK ; Kyung Chul YOON ; Ji Shin LEE ; Shin Seok LEE
Journal of Korean Medical Science 2016;31(2):190-195
We investigated the clinical and biological significance of germinal centers (GC) present in the minor salivary glands of patients with Sjogren's syndrome (SS). Minor salivary gland tissue biopsies from 93 patients with SS were used to identify GC-like structures, which were confirmed by CD21-positive follicular dendritic cell networks. Patients were compared based upon sociodemographics, glandular and extraglandular manifestations, and laboratory findings including autoantibody profiles, complement, and immunoglobulin levels; EULAR SS disease activity index (ESSDAI) and SS disease damage index (SSDDI) were also measured. GC-like structures were observed in 28 of 93 SS patients (30.1%). Mean focus scores and CRP levels were significantly higher in GC-positive patients than in GC-negative patients; GC-positive patients also exhibit a higher prevalence of rheumatoid factor and anti-SS-A/Ro antibodies compared to GC-negative patients. No differences in glandular or extra-glandular manifestations were evident between groups. In conclusion, SS patients with GC-like structures in the minor salivary glands exhibited laboratory profiles significantly different from those of their GC-negative counterparts. Long-term follow-up of these patients will be necessary to determine whether these laboratory abnormalities are predictive of clinical outcomes.
Adult
;
Autoantibodies/blood
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C-Reactive Protein/analysis
;
Demography
;
Female
;
Germinal Center/*pathology
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Humans
;
Immunohistochemistry
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Male
;
Middle Aged
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Receptors, Complement 3d/metabolism
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Retrospective Studies
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Salivary Glands, Minor/*pathology
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Sjogren's Syndrome/immunology/metabolism/*pathology
8.The Significance of Ectopic Germinal Centers in the Minor Salivary Gland of Patients with Sjogren's Syndrome.
Kyung Eun LEE ; Ji Hyoun KANG ; Yi Rang YIM ; Ji Eun KIM ; Jeong Won LEE ; Lihui WEN ; Dong Jin PARK ; Tae Jong KIM ; Yong Wook PARK ; Kyung Chul YOON ; Ji Shin LEE ; Shin Seok LEE
Journal of Korean Medical Science 2016;31(2):190-195
We investigated the clinical and biological significance of germinal centers (GC) present in the minor salivary glands of patients with Sjogren's syndrome (SS). Minor salivary gland tissue biopsies from 93 patients with SS were used to identify GC-like structures, which were confirmed by CD21-positive follicular dendritic cell networks. Patients were compared based upon sociodemographics, glandular and extraglandular manifestations, and laboratory findings including autoantibody profiles, complement, and immunoglobulin levels; EULAR SS disease activity index (ESSDAI) and SS disease damage index (SSDDI) were also measured. GC-like structures were observed in 28 of 93 SS patients (30.1%). Mean focus scores and CRP levels were significantly higher in GC-positive patients than in GC-negative patients; GC-positive patients also exhibit a higher prevalence of rheumatoid factor and anti-SS-A/Ro antibodies compared to GC-negative patients. No differences in glandular or extra-glandular manifestations were evident between groups. In conclusion, SS patients with GC-like structures in the minor salivary glands exhibited laboratory profiles significantly different from those of their GC-negative counterparts. Long-term follow-up of these patients will be necessary to determine whether these laboratory abnormalities are predictive of clinical outcomes.
Adult
;
Autoantibodies/blood
;
C-Reactive Protein/analysis
;
Demography
;
Female
;
Germinal Center/*pathology
;
Humans
;
Immunohistochemistry
;
Male
;
Middle Aged
;
Receptors, Complement 3d/metabolism
;
Retrospective Studies
;
Salivary Glands, Minor/*pathology
;
Sjogren's Syndrome/immunology/metabolism/*pathology
9.Recurrent Ophthalmoplegia Presenting Different Clinical Features in a Patient with Anti-GQ1b Antibody Syndrome.
Kwang Hoon SHIN ; Hyun Taek LIM
Korean Journal of Ophthalmology 2016;30(4):314-315
No abstract available.
Adult
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Autoantibodies/*blood
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Gangliosides/blood/*immunology
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Humans
;
Male
;
Ophthalmoplegia/blood/*diagnosis/immunology
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Recurrence
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Syndrome
10.Influence of Anticoagulants on Detection of ITP Platelet-Specific Autoantibodies and Relationship of Autoantibody Types with Glucocorticoid Efficacy.
Yang CHEN ; Jian GE ; Min RUAN ; Lin-Yang ZHU ; Qing-Shu ZENG ; Rui-Xiang XIA ; He-Yu NI
Journal of Experimental Hematology 2015;23(5):1380-1385
OBJECTIVETo investigate the influence of divalent cation chelator EDTA and heparin sodium on the detection of ITP platelet-specific autoantibodies by the modified monoclonal antibody immobilization of platelet antigen assay (MAIPA) and to explore the relationship between types of platelet specific autoantibodies and glucocorticoid efficacy.
METHODSThe samples were obtained from EDTA- and heparin- anticoagulant ITP patients, respectively, so as to detect the platelet-specific autoantibodies (GPIIb/IIIa and GPIbα) in 140 ITP samples by modified MAIPA, then the differences between these two methods were compared.
RESULTSOut of 140 cases in EDTA group, 55 cases were positive for GPIIb/IIIa, while 76 cases in heparin group were positive for GPIIb/IIIa, 42 cases in both group were repeatable; among them 13 cases were positive in EDTA group and negative in heparin group, while 34 cases were positive in heparin group and negative in EDTA group, there was significant difference between them (x (2) = 9.38, P < 0.05), 62 cases in 140 cases of EDTA group were positive for GPIba, while 51 cases in heparin group were positive for GPIba, 42 cases in both group were repeatabe; among them 20 cases were positive in EDTA group and negative in heparin group, while 9 cases were positive in heparin group and negative in EDTA group, there was no significant difference between them (x (2) = 3.44, P > 0.05). A total of 320 cases received a standard glucocorticoid treatment, out of them 143 cases were positive for GPIbα with effective rate 39.9%, 177 cases were negative for GPIbα with effective rate 79.7%, there was statisticalty significant difference between them (x (2) = 53.115, P < 0.05).
CONCLUSIONEDTA anticoagulant (a divalent cation chelator) has a significant influence on detection of ITP platelet-specific autoantibodies (GPIIb/IIIa) by a modified MAIPA method and the GPIbα antibody positive may be one of the important factors that results in un-sensitivity of ITP patients to glucocorticoid treatment.
Antibodies, Monoclonal ; Anticoagulants ; therapeutic use ; Antigens, Human Platelet ; Autoantibodies ; blood ; Blood Platelets ; immunology ; Fibrinolytic Agents ; Glucocorticoids ; therapeutic use ; Heparin ; Humans ; Platelet Glycoprotein GPIIb-IIIa Complex ; Purpura, Thrombocytopenic, Idiopathic ; blood ; immunology

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