scholarly journals Denosumab as the Treatment of Recalcitrant Tuberculous Pleural Effusion-Associated Hypercalcemia

2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Afdhal Afiq Abd Jalil ◽  
Sharifah Faradila Wan Muhamad Hatta ◽  
Aimi Fadilah Mohamad ◽  
Mohammed Fauzi Abdul Rani
Keyword(s):  
Monoclonal Antibody ◽  
Pleural Effusion ◽  
Calcium Level ◽  
Nuclear Factor Kappa B ◽  
Human Monoclonal Antibody ◽  
Nuclear Factor ◽  
Treatment Of Osteoporosis ◽  
Tuberculous Pleural Effusion ◽  
Receptor Activator ◽  
Granulomatous Diseases

Denosumab is a human monoclonal antibody that binds to RANKL (receptor activator of nuclear factor-kappa B ligand). It has mainly been used in the treatment of osteoporosis for a variety of causes especially in situations refractory to bisphosphonates or when kidney function is impaired. It is also used in cases of malignancy-associated hypercalcemia. There are many causes of hypercalcemia, but only rarely it is associated with granulomatous diseases such as tuberculous pleural effusion. We report a case of hypercalcemia from tuberculous pleural effusion that was initially admitted with left medium abundance pleural effusion and a serum corrected calcium level of 3.48 mmol/L. The calcium level was successfully normalized within 72 hours of subcutaneous denosumab administration after other interventions have failed.

scholarly journals Expression and Functional Evaluation of Recombinant Anti-receptor Activator of Nuclear Factor Kappa-B Ligand Monoclonal Antibody Produced in Nicotiana benthamiana

2021 ◽  
Vol 12 ◽  
Author(s):  
Wanuttha Boonyayothin ◽  
Sirorut Sinnung ◽  
Balamurugan Shanmugaraj ◽  
Yoshito Abe ◽  
Richard Strasser ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Nicotiana Benthamiana ◽  
Nuclear Factor Kappa B ◽  
Human Monoclonal Antibody ◽  
Affinity Column ◽  
Functional Evaluation ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Receptor Activator

Denosumab, an anti-receptor activator of nuclear factor-kappa B ligand antibody (anti-RANKL), is a fully human monoclonal antibody (mAb) available for the treatment of osteoporosis. In the present study, an anti-RANKL mAb was transiently expressed using the geminiviral expression system in Nicotiana benthamiana, and the functional activity of the plant-produced mAb was determined. The highest expression level of the plant-produced mAb was found at 8 days post-infiltration, and it was estimated to be 0.5 mg/g leaf fresh weight. The recombinant mAb from the plant crude extracts was purified by using Protein A affinity column chromatography. The plant-produced mAb demonstrated good in vitro affinity binding with human RANKL, as determined by RANKL-ELISA binding. The function of the plant-produced mAb was evaluated in vitro. CD14-positive cells isolated from human peripheral blood mononuclear cells (PBMCs) were cultured in vitro in the presence of human RANKL and macrophage-colony-stimulating factor (M-CSF) to stimulate osteoclastogenesis. The results demonstrated that plant-produced mAb could significantly decrease the number of osteoclasts compared to commercial denosumab. These results demonstrated that the plant-produced mAb has the potential to inhibit osteoclast differentiation and that it could be considered for osteoporosis treatment.

Mo1699 Denosumab: A Monoclonal Antibody to Receptor Activator of Nuclear Factor-Kappa B Ligand (RANKL) Decreases Experimental Colitis

2015 ◽  
Vol 148 (4) ◽  
pp. S-688-S-689
Author(s):  
Azin Khafipour ◽  
Peris M. Munyaka ◽  
Hongxing Wang ◽  
Nour Eissa ◽  
Charles N. Bernstein ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Nuclear Factor Kappa B ◽  
Experimental Colitis ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Receptor Activator

scholarly journals Osteoporosis in thalassaemia

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Ersi Voskaridou ◽  
Maria Dimopoulou ◽  
Evangelos Terpos
Keyword(s):  
Bone Resorption ◽  
Nuclear Factor Kappa B ◽  
Human Monoclonal Antibody ◽  
Osteoclast Differentiation ◽  
Osteoclast Formation ◽  
Nuclear Factor ◽  
Receptor Activator ◽  
Formation Function ◽  
And Function ◽  
Markers Of Bone Resorption

Osteoporosis is a prominent cause of morbidity in patients with thalassaemia major (TM) with a complex pathophysiology. Patients with TM and osteoporosis have elevated markers of bone resorption. This increased osteoclast activity seems to be at least partially due to an imbalance in the receptor–activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) system, which is of great importance for the regulation of osteoclast differentiation and function. Denosumab is a fully human monoclonal antibody that binds to RANKL and thereby inhibits the activation of osteoclasts by RANKL. By blocking RANKL, denosumab inhibits osteoclast formation, function and survival, thereby decreasing bone resorption and increasing bone mass in postmenopausal women and patients with thalassaemia-induced osteoporosis.

scholarly journals A case of minimal change disease after the administration of anti receptor activator of nuclear factor kappa B ligand (RANKL) monoclonal antibody: a case report

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Keisuke Horikoshi ◽  
Norihiko Sakai ◽  
Naoki Yamamoto ◽  
Hisayuki Ogura ◽  
Koichi Sato ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Nephrotic Syndrome ◽  
Minimal Change Disease ◽  
Nuclear Factor Kappa B ◽  
Kidney Diseases ◽  
Minimal Change ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Urinary Protein Level ◽  
Receptor Activator

Abstract Background Minimal change disease (MCD) is one of the causes of idiopathic nephrotic syndrome in adults. The pathogenesis of proteinuria in MCD has not been fully understood. Recently, it has been reported that the receptor activator of nuclear factor-kappa B (RANK)/RANK ligand (RANKL) may contribute to the podocyte biology in kidney diseases. Denosumab is a human anti-RANKL monoclonal antibody used to treat osteoporosis. Here we report a case of MCD after denosumab administration. Case presentation A 59-year-old male without any episodes of proteinuria was given denosumab to treat osteoporosis. Two weeks after its administration, he noticed a foamy urine and bilateral pretibial edema. Laboratory tests revealed that he had severe proteinuria (15g/g Cr), hypoproteinemia (4.0g/dL), and hypoalbuminemia (1.5g/dL). Based on the results, he was diagnosed with nephrotic syndrome. The proteinuria selectivity index was 0.05, indicating selective proteinuria. Renal biopsy showed minor glomerular abnormality with less tubulointerstitial damage, and electron microscopy showed extensive foot process effacement, indicating MCD. With all these results, glucocorticoid therapy of 50mg/day prednisolone was started. After 4weeks of treatment, the urinary protein level remains high (3.1g/g Cr). Prednisolone therapy was continued, and the levels of proteinuria decreased gradually to the range of partial remission (1.2g/g Cr) with another 7weeks of prednisolone treatment, but complete remission was not achieved. Conclusions This might be a case wherein RANKL inhibition is associated with the pathogenesis of MCD. Further studies will be needed to elucidate the causal relationship of RANK-RANKL signaling to the pathogenesis of MCD.

scholarly journals QiangGuYin Modulates the OPG/RANKL/RANK Pathway by Increasing Secretin Levels during Treatment of Primary Type I Osteoporosis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Xuefei Li ◽  
Longkang Cui ◽  
Wenhua Chen ◽  
Yuan Fang ◽  
Gaobo Shen ◽  
...  
Keyword(s):  
Nuclear Factor Kappa B ◽  
Underlying Mechanism ◽  
Type I ◽  
Nuclear Factor ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Treatment Of Osteoporosis ◽  
Nuclear Factor Kappa ◽  
Receptor Activator ◽  
Primary Type

QiangGuYin (QGY) is a common Traditional Chinese medicine prescription for the treatment of osteoporosis. Previous clinical studies have found that QGY effectively improves bone mineral density (BMD) in postmenopausal women, but its underlying mechanism remains unclear. The osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL)/receptor activator of nuclear factor kappa B (RANK) pathway is a classic pathway involved in osteoporosis. Secretin levels are a serum marker of osteoporosis, but their effect on the OPG/RANKL/RANK pathway has not been reported. Hence, we investigated the relationship between the OPG/RANKL/RANK pathway and secretin and further revealed the mechanism underlying the effect of QGY in the treatment of osteoporosis. Mice were divided into secretin knockdown, secretin overexpression, and corresponding control groups. Micro-computed tomography was used to detect BMD in different groups, and the results show that QGY significantly improved BMD in mice of the secretin knockdown group. To further verify this, the serum levels of OPG, RANKL, RANK, and secretin were measured by enzyme-linked immunosorbent assays, and femur levels of OPG, RANKL, RANK, and secretin were evaluated by real-time quantitative PCR and western blotting. The results show that the expression of OPG was inhibited and that of RANKL and RANK was increased in mice from the secretin knockdown group, whereas the expression of OPG was upregulated and that of RANKL and RANK was downregulated after QGY intervention. Therefore, QGY inhibited bone resorption by promoting the expression of secretin and modulating the OPG/RANKL/RANK pathway. In addition to the effect of QGY, we also revealed the general regulatory effect of secretin on the OPG/RANKL/RANK pathway. We conclude that QGY modulates the OPG/RANKL/RANK pathway by increasing secretin levels during treatment of primary type I osteoporosis. This work provides a theoretical basis for the clinical use of QGY in the treatment of osteoporosis.

Osteoprotegerin (OPG) levels, total soluble receptor activator of nuclear factor-Kappa B ligand (total sRANKL) , and RANKL/OPG ratio in patients with rheumatoid arteritis

2017 ◽  
Vol 2 (1) ◽  
pp. 23-29
Author(s):  
Sousan Kolahi ◽  
Amir Ghorbanihaghjo ◽  
Nadereh Rashtchizadeh ◽  
Alireza Khabbazi ◽  
Mehrzad Hajialilo ◽  
...  
Keyword(s):  
Nuclear Factor Kappa B ◽  
Nuclear Factor ◽  
Soluble Receptor ◽  
Nuclear Factor Kappa ◽  
Receptor Activator
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