1.Folate Receptor-Targeted Diagnostics and Therapeutics for Inflammatory Diseases.
Immune Network 2016;16(6):337-343
Inflammation, an innate immune response mediated by macrophages, forms the first line of defence to protect our body from the invasion of various pathogens. Although inflammation is a defensive response, chronic inflammation has been regarded as the major cause of many types of human diseases such as inflammatory/autoimmune diseases, cancers, neurological diseases, and cardiovascular diseases. Folate receptor (FR) is a cell surface glycosylphosphatidylinositol (GPI)-anchored glycoprotein, and its three isoforms, FR-α, FR-β, and FR-γ, are found in humans. Interestingly, FRs are highly expressed on a variety of cells, including cancer cells and activated macrophages, whereas their expression on normal cells is undetectable, indicating that FR-targeting could be a good selective strategy for the diagnosis and therapeutic treatment of cancers and activated macrophage-mediated inflammatory diseases. Previous studies successfully showed FR-targeted imaging of many types of cancers in animal models as well as human patients. Recently, a number of emerging studies have found that activated macrophages, which are critical players for a variety of inflammatory diseases, highly express FRs, and selective targeting of these FR-positive activated macrophages is a good approach to diagnose and treat inflammatory diseases. In this review, we describe the characteristics and structure of FRs, and further discuss FR-targeted diagnostics and therapeutics of human diseases, in particular, activated macrophage-mediated inflammatory diseases.
Cardiovascular Diseases
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Diagnosis
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Folic Acid*
;
Glycoproteins
;
Glycosylphosphatidylinositols
;
Humans
;
Immunity, Innate
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Inflammation
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Macrophages
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Models, Animal
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Protein Isoforms
3.Glycosylphosphatidylinositol biosynthesis deficiency 15 caused by GPAA1 gene mutation: a rare disease study.
Qiu-Rong CHEN ; Zhen-Jie ZHANG ; Yi-Xiu LU ; Sun-Bi-Xin YUAN ; Ji LI
Chinese Journal of Contemporary Pediatrics 2023;25(12):1276-1281
A boy, aged 6 years, attended the hospital due to global developmental delay for 6 years and recurrent fever and convulsions for 5 years. The boy was found to have delayed mental and motor development at the age of 3 months and experienced recurrent fever and convulsions since the age of 1 year, with intermittent canker sores and purulent tonsillitis. During the fever period, blood tests showed elevated white blood cell count, C-reactive protein, and erythrocyte sedimentation rate, which returned to normal after the fever subsides. Electroencephalography showed epilepsy, and genetic testing showed compound heterozygous mutations in the GPAA1 gene. The boy was finally diagnosed with glycosylphosphatidylinositol biosynthesis deficiency 15 (GPIBD15) and periodic fever. The patient did not respond well to antiepileptic treatment, but showed successful fever control with glucocorticoid therapy. This article reports the first case of GPIBD15 caused by GPAA1 gene mutation in China and summarizes the genetic features, clinical features, diagnosis, and treatment of this disease, which provides a reference for the early diagnosis and treatment of GPIBD15.
Humans
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Male
;
Fever
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Glycosylphosphatidylinositols/genetics*
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Membrane Glycoproteins/genetics*
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Mutation
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Rare Diseases
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Seizures
;
Child
4.Trypanosome Glycosylphosphatidylinositol Biosynthesis.
Yeonchul HONG ; Taroh KINOSHITA
The Korean Journal of Parasitology 2009;47(3):197-204
Trypanosoma brucei, a protozoan parasite, causes sleeping sickness in humans and Nagana disease in domestic animals in central Africa. The trypanosome surface is extensively covered by glycosylphosphatidylinositol (GPI)-anchored proteins known as variant surface glycoproteins and procyclins. GPI anchoring is suggested to be important for trypanosome survival and establishment of infection. Trypanosomes are not only pathogenically important, but also constitute a useful model for elucidating the GPI biosynthesis pathway. This review focuses on the trypanosome GPI biosynthesis pathway. Studies on GPI that will be described indicate the potential for the design of drugs that specifically inhibit trypanosome GPI biosynthesis.
Animals
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Biosynthetic Pathways
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Glycosylphosphatidylinositols/*biosynthesis/chemistry
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Humans
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Protozoan Proteins/genetics/metabolism
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Trypanosoma brucei brucei/chemistry/genetics/*metabolism
;
Trypanosomiasis, African/*parasitology
5.Trypanosome Glycosylphosphatidylinositol Biosynthesis.
Yeonchul HONG ; Taroh KINOSHITA
The Korean Journal of Parasitology 2009;47(3):197-204
Trypanosoma brucei, a protozoan parasite, causes sleeping sickness in humans and Nagana disease in domestic animals in central Africa. The trypanosome surface is extensively covered by glycosylphosphatidylinositol (GPI)-anchored proteins known as variant surface glycoproteins and procyclins. GPI anchoring is suggested to be important for trypanosome survival and establishment of infection. Trypanosomes are not only pathogenically important, but also constitute a useful model for elucidating the GPI biosynthesis pathway. This review focuses on the trypanosome GPI biosynthesis pathway. Studies on GPI that will be described indicate the potential for the design of drugs that specifically inhibit trypanosome GPI biosynthesis.
Animals
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Biosynthetic Pathways
;
Glycosylphosphatidylinositols/*biosynthesis/chemistry
;
Humans
;
Protozoan Proteins/genetics/metabolism
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Trypanosoma brucei brucei/chemistry/genetics/*metabolism
;
Trypanosomiasis, African/*parasitology
6.Eukaryotic expression of P-selectin functional segment on the membrane of CHO.
Xiaofang LOU ; Shuang WANG ; Weishi DU ; Rui YU ; Weiyuan YU ; Zhiwei SUN
Chinese Journal of Biotechnology 2008;24(7):1162-1167
Cell adhesive molecular P-selectin was cloned, expressed and anchored on CHO cell membrane through GPI for selection specific antibodies. Total human platelet RNA was extracted and the functional segment of P-selectin gene was cloned by RT-PCR. The P-selectin functional segment gene was cloned into a eukaryotic expression vector pMCEw2-GPI containing an attenuated neo gene together with a downstream GPI, which was synthesized by overlapping PCR. The recombinant plasmid pMCEw2-GPI-P-selectin was then transfected to CHO(dhfr-) cells and screened with G418. ELISA, western-blot and immunofluorescence were carried out to detect the stability of P-selection expression on cell membrane. These results provided a necessary basis for the following study of selection the antibodies targeting P-selectin.
Animals
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Antibodies
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metabolism
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CHO Cells
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Cell Membrane
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metabolism
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Cloning, Molecular
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Cricetinae
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Cricetulus
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Epidermal Growth Factor
;
metabolism
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Glycosylphosphatidylinositols
;
metabolism
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Lectins
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metabolism
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P-Selectin
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biosynthesis
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genetics
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immunology
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RNA
;
metabolism
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Transfection
7.Estimation of expression of glycosylphosphatidylinositol-anchored protein in B lymphocytes for diagnosis of paroxysmal nocturnal hemoglobinuria.
Acta Academiae Medicinae Sinicae 2003;25(5):599-602
OBJECTIVETo estimate whether the expression of glycosylphosphatidylinositol (GPI)-anchored protein in B lymphocytes could be an indicator for detecting paroxysmal nocturnal hemoglobinuria (PNH).
METHODSFlow cytometry and two-color McAbs were used to detect CD59 expression in B lymphocytes and granulocytes of 92 clinical samples. The feasibility of the indicators for diagnosis of PNH was assessed.
RESULTSB lymphocytes from healthy individuals mainly showed a single population of cells strongly positive for CD59, as the percentage of CD59 expression was (96.3 +/- 1.2)%. In PNH patients, B lymphocytes showed decreased expression of CD59, as well as negative cells and partly-positive cells were observed, as the percentage of CD59 expression was 10.5%-92.3%. In 26 of 28 non-PNH anemia patients, CD59 expression in B lymphocyte was normal, and in the other 2 patients, CD59 expression were decreased (< 95%), but no negative cell peak was observed. The precision CV of CD59 in B lymphocyte assay is less than 4.4%, stained samples could be kept stable for 24 h, the CD59 in B lymphocyte assay was 100% in accordance with routine assay (CD59 in granulocyte assay). The sensitivity of the indicators (CD59 in B lymphocytes and granulocytes) was 100%, the specificity was 97.4%, misdiagnosis rate was 2.6%, the rate of failing to diagnosis was 0%, the rate of positive forecast was 87.5%, the rate of negative forecast was 100%, the accuracy was 97.8%.
CONCLUSIONSThe test of CD59 expression in B lymphocytes by flow cytometry was simple, accurate and reproduceable. It could be a good marker for diagnosis of PNH because of high sensitivity and specificity.
B-Lymphocytes ; metabolism ; Biomarkers ; CD59 Antigens ; blood ; Female ; Flow Cytometry ; Glycosylphosphatidylinositols ; biosynthesis ; Granulocytes ; metabolism ; Hemoglobinuria, Paroxysmal ; diagnosis ; Humans ; Male ; Membrane Proteins ; metabolism ; Sensitivity and Specificity
8.Preliminary study of DA or HA regimen chemotherapy for the treatment of refractory and relapsed paroxysmal nocturnal hemoglobinuria.
Yan-ran CAO ; Zong-hong SHAO ; Hai-rong JIA ; Juan SUN ; Hong LIU ; Yu-hong WU ; Tie-jun QIN ; Jun SHI ; Jie BAI ; Guang-sheng HE ; Rong FU ; Ming-feng ZHAO ; Hai-feng TU ; Zhen-zhu CUI ; Tian-ying YANG
Chinese Journal of Hematology 2004;25(4):202-204
OBJECTIVETo observe the efficacy and side effect of DA/HA regimen chemotherapy for the treatment of refractory and relapsed paroxysmal nocturnal hemoglobinuria (PNH).
METHODSEight patients with refractory and relapsed PNH were treated with DA/HA regimen chemotherapy. Three patients were treated with DA (DNR 40 mg/d, i.v.drip, the first and the second day; 20 mg/d, i.v.drip, the third day; Ara-C 100 mg/d, i.v.drip, for 5 days) and 5 patients with HA (HHT 2 - 3 mg/d, i.v.drip, for 5 days; Ara-C 100 mg/d, i.v.drip, for 5 days).
RESULTSAll the 8 patients responded well: the PNH clone was diminished in five patients. Hemolysis was remitted in 6 cases. Five patients showed improvement in hematological parameters. The dosage of corticosteroid was decreased in all of them. No serious side effect was revealed.
CONCLUSIONDA/HA regimen chemotherapy was safe and effective for refractory and relapsed PNH patients.
Adolescent ; Adult ; Cytarabine ; administration & dosage ; Daunorubicin ; administration & dosage ; Drug Therapy, Combination ; Female ; Glycosylphosphatidylinositols ; analysis ; Harringtonines ; Hemoglobinuria, Paroxysmal ; drug therapy ; Humans ; Male
9.A Case of Coexistence with Myelodysplastic Syndrome and Paroxysmal Nocturnal Hemoglobinuria: Confirmed by Reticulocytes Survival Test and Glycosylphosphatidylinositol (GPI)-linked Protein Test.
Ji Hyang LIM ; Yonggoo KIM ; Dong Wook KIM ; Jong Yul JIN ; Chi Wha HAN ; Kyungja HAN ; Sang In SHIM ; Chun Choo KIM
Korean Journal of Hematology 1997;32(3):465-469
A patient presenting paroxysmal nocturnal hemoglobinuria (PNH) cloned cells in the course of myelodysplastic syndrome (MDS) with reticulocytosis is described. The bone marrow biopsy demonstrated erythroid hyperplasia and moderate dysplasia. Mild hemoglobinuria was detected but the Ham test was negative. The reticulocyte survival test revealed sustained survival curve indicating delayed reticulocyte maturation regarded as the characteristic of MDS cloned erythroid cells. The glycosylphosphatidylinositol-linked protein deficient neutrophils and erythrocytes population regarded as PNH clones were identified by flow cytometric analysis using monoclonal antibody. From these results, we concluded that MDS and PNH cloned cells were coexisited in this patient. In this patient, long-term follow-up observation could clarify whether MDS and PNH were arising from the same clone or from two distinct clones.
Biopsy
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Bone Marrow
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Clone Cells
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Erythrocytes
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Erythroid Cells
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Follow-Up Studies
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Glycosylphosphatidylinositols*
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Hemoglobinuria
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Hemoglobinuria, Paroxysmal*
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Humans
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Hyperplasia
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Myelodysplastic Syndromes*
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Neutrophils
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Reticulocytes*
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Reticulocytosis
10.Expression of three kinds of GPI-anchor proteins in paroxysmal nocturnal hemoglobinuria, aplastic anemia and myelodysplastic syndromes patients and their clinical implications.
Xiao-yuan DONG ; Cong-gao XU ; Guo-rui SUN ; Ti ZHANG ; Jun PENG
Chinese Journal of Hematology 2004;25(4):198-201
OBJECTIVETo investigate the expressions of three kinds of glycosyl-phosphatidylinositol anchor proteins (GPI-AP), the CD(55), CD(59) and CD(87) on the peripheral granulocytes and the soluble u-PAR (su-PAR) level in serum from patients with paroxysmal nocturnal hemoglobinuria (PNH), aplastic anemia (AA), and myelodysplastic syndromes (MDS), and to analyse their clinical implications.
METHODSTwenty-two PNH patients, including 4 complicated with thrombotic diseases and 5 with AA-PNH syndrome, 30 AA patients, including 9 being severe AA (SAA) and 11 chronic AA (CAA), 27 MDS-RA patients, and 20 healthy individuals were tested. The expressions of CD(55), CD(59) and CD(87) on peripheral granulocytes were analyzed with flow cytometry. Serum su-PAR was assayed by ELISA.
RESULTSThe CD(55)(+), CD(59)(+) and CD(87)(+) granulocytes in peripheral blood of 20 normal controls were all more than 90%. The expressions of three kinds of GPI-APs in 22 PNH patients were significantly decreased as compared with that in normal controls, AA patients and MDS-RA patients. The serum level of su-PAR in PNH group was higher than that of the other three groups. The expression of CD(87) was significantly decreased in thrombotic PNH patients as compared with that in non-thrombotic PNH patients. The expression of CD(87) was significantly decreased in AA patients than in normal controls. The expressions of three kinds of GPI-APs in 5 AA-PNH syndrome patients were remarkably reduced as compared with AA patients, but no significant difference was found for these indexes between AA-PNH syndrome and PNH patients and between 27 MDS-RA patients and 20 normal controls.
CONCLUSIONMeasurement of CD(55), CD(59) and CD(87) expressions levels on the peripheral granulocytes and su-PAR in serum would be alternative approaches for diagnosis and differential diagnosis of PNH. Serum level of su-PAR may be helpful to monitor thrombosis in PNH patients.
Adult ; Aged ; Anemia, Aplastic ; blood ; CD55 Antigens ; blood ; CD59 Antigens ; blood ; Female ; Glycosylphosphatidylinositols ; blood ; Hemoglobinuria, Paroxysmal ; blood ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; blood ; Receptors, Cell Surface ; blood ; Receptors, Urokinase Plasminogen Activator