3 case studies: antibodies are valuable tools in clinical research
Atlas Antibodies, October 2019
Applied biological or biomedical research aims to reach a thorough understanding of the physiology of organisms and to further development of disease therapeutics. Some scientific discoveries have narrow applicability or scope and are sometimes serendipitous or even entirely unexpected. Other have wider applicability and transferability having proved enormously useful over a wide range of domains. Among the latter are research antibodies. Read more to discover how they help progressing science.
Secure the future of science by enabling the science for the future
Over the past 50 years, we have observed an outstanding array of breakthroughs that push science to new heights. Advances in technological and computational capabilities continues to unravel novel research fields which have been previously out of our reach. Just consider our atomic-scale understanding of materials, the integration of artificial intelligence (AI) into our everyday life, or the intersection between the central nervous system and microelectronics leading to astonishing advances in basic and clinical neuroscience.
Research antibodies: powerful tools for progressing science
Research antibodies have come a long way from their earliest reference back in 1890. Today, they are central to basic research and used in a wide range of bioscience disciplines such as in cancer research, neuroscience, cell biology, regenerative medicine and immunology research.
Immunohistochemistry (IHC) is the principal antibody-based application and is applied to determine the tissue distribution of an antigen of interest in health and disease in both diagnostic settings and for research purposes (Duraiyan J et al. 2012).
In oncology for example, IHC is widely used for tumor diagnosis: specific cancer antigens are expressed de novo or upregulated in certain neoplasias. By using antibodies against specific tumor markers, researchers and physicians use IHC to identify and diagnose cancer as benign or malignant, to determine the stage and grade of a tumor, and to recognize the cell type.
In neuroscience, understanding the causes of neurodegenerative diseases involves studies aimed to localize and quantify the abnormal proteins that cause neurodegenerative diseases such as the deposition of beta-amyloid, the cytoplasmic accumulations of alpha-synuclein, etc. IHC combined with primary antibodies specifically recognizing beta-amyloid, alpha-synuclein, ubiquitin, huntingtin, polyglutamine, and others have become a routine tool for sensitive detection and quantification of these abnormal proteins in human tissues and in experimental animal models of the human diseases.
Antibodies impact scientific research: 3 case studies
The essential role of the antibodies in advancing scientific knowledge is supported by thousands of publications. Here we present three examples of scientific discoveries that could impact patient’s survival and wellbeing.
Case study 1: Immunohistochemistry improves the molecular classification of adult’s diffuse gliomas in daily practice
Human α thalassemia/mental retardation syndrome X-linked (ATRX) mutations lead to the development of thalassemia, mental retardation, α-thalassemia X-linked mental retardation and other genetic conditions. ATRX mutations are present in at least 15 types of human tumors, including neuroblastoma, osteosarcoma and pancreatic neuroendocrine tumors.
Although the role of ATRX in tumorigenesis remains to be elucidated, mutations ATRX genes have been the subject of numerous studies on the classification and prognosis of glioma, a type of tumor that occurs in the brain and spinal cord. Gliomas can be classified into different pathological grades. Unfortunately, the classification of the World Health Organization (WHO) for the pathological grades of gliomas is still somewhat unclear.
In a recent study published in Oncology Letters (Liu J et al. 2019) the Anti-ATRX antibody and other markers, helped in providing the theoretical basis for further research aimed to improve the clinical diagnosis, the classification and thus the treatment of glioma.
Here you will find a list of publications featuring the Anti-ATRX antibody (HPA001906).
Figure 1. Example of immunohistochemistry analysis in human cerebral cortex and liver tissues using the Anti-ATRX Antibody (HPA001906). Corresponding ATRX RNA-seq data are presented for the same tissues.
Case study 2: Stroke patients may benefit from an anti‐inflammatory therapy
Many studies have shown the presence of inflammation in the lesions of experimental stroke models. Inflammatory mechanisms, involving macrophages and activated microglia play a pathogenic role in experimental models of stroke, and may be useful targets for stroke therapy. However, microglia and macrophages share a common lineage, which is why many markers fail to distinguish these two cell types apart.
The transmembrane protein 119 (TMEM119) is a cell-surface and a specific microglial marker which is expressed on all resting microglia in the rodent and human brain. The advantage over other microglial markers is that TMEM119 is not expressed by macrophages or other cell types.
In a recent study published in Brain Pathology (Zrzavy T. et al. 2018), the authors used TMEM119 as a marker for the resident microglia pool, to perform a quantitative study on the inflammatory reaction in human ischemic infarct lesions. They analyzed the infiltration of lymphocytes, granulocytes and recruited monocytes and the activation state of microglia in different stages of the evolution of the human ischemic infarct lesions. The results of this study show that a stroke therapy targeting pro‐inflammatory microglia and macrophage activation may be effective in stroke patients.
Here you will find a list of publications featuring the Anti-TMEM119 antibody.
Figure 2. Example of Anti-TMEM119 Antibody (HPA051870) immunohistochemistry staining of cerebral cortex (A), lymph node (B) and liver (C) tissues. The corresponding RNA-seq data for lymp node and liver tissues are presented in D (orthogonal antibody validation).
Case study 3: Japanese patients with nephrotic syndrome have the lowest levels of phospholipase A2 receptors
Membranous Nephropathy (MN) is a kidney disease that affects the filters (glomeruli) of the kidney and can cause release of protein into the urine, as well as decreased kidney function. For more than 50 years researchers have debated the evidence for an autoimmune basis of MN. Work published in recent years has substantially strengthened the belief that MN is indeed an autoimmune disease of the kidney.
Since approximately 70% of patients with idiopathic MN (iMN) has autoantibodies to Phospholipase A2 receptor 1 (PLA2R1) in their serum, PLA2R1 is considered a major target antigen for MN.
Remarkably, a study published in Clinical and Experimental Nephrology (Akiyama S. et al. 2015) used western blot with anti-PLA2R1 antibody to show that the prevalence of PLA2R1 auto-antibodies was lower in Japanese patients with iMN compared to any other Asian country, USA and Europe (Akiyama S. et al. 2015). This may indicate that the presence of other pathogenic antigens plays a significant role in Japanese patients with iMN.
Here you will find a list of publications featuring the Anti-PLA2R1 antibody.
Figure 3. Example of immunohistochemistry analysis of Phospholipase a2 receptor 1 in human kidney and pancreas tissues using Anti-PLA2R1 Antibody (HPA012657). Corresponding PLA2R1 RNA-seq data are presented for the same tissues.
Duraiyan J et al. (2012) Applications of immunohistochemistry. J Pharm Bioallied Sci. 4(Suppl 2): S307- S309
Liu J. et al. (2019) Significance of TERT and ATRX mutations in glioma. Oncol Lett. 17(1):95-102
Zrzavy T. et al. (2018) Dominant role of microglial and macrophage innate immune responses in human ischemic infarcts. Brain Pathol. 28(6): 791–805.
Akiyama S. et al. (2015) Prevalence of anti-phospholipase A2 receptor antibodies in Japanese patients with membranous nephropathy. Clin Exp Nephrol.19(4): 653–660.
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