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The University of Southampton
Medicine

New insight into antibody activity

Published: 16 February 2018
Immune complexes insight
New insight into antibody activity

Scientists from the Antibody and Vaccine Group have developed a novel in vitro cell-based method for the detection of antibody immune complexes.

Immune complexes are made when an antibody binds to its target. Usually these complexes get cleared but in some autoimmune diseases they accumulate and can interfere with normal antibody functions and cause disease.

The new method, published in the Journal of Immunology, couples the known functions of a family of cell surface receptors with fundamental roles in regulation of the immune system called Fc gamma receptors, and a novel technology for detecting protein:protein interactions.

Crucially, the method is capable of discriminating between single antibodies and antibodies that are bound together in a complex. Although usually required for normal immune system function these immune complexes can cause unwanted effects in the setting of various autoimmune diseases, such as Rheumatoid Arthritis or Systemic Lupus Erythrematosis.

The study, which was done in collaboration with colleagues in Germany and the USA, alongside clinicians at UCL London, used novel NanoBiT™ technology developed by Promega corporation to produce a new investigative procedure which signals detection of immune complex by the transmission of light.

Professor Mark Cragg, who led the study, said: “Light is generated by an enzyme called luciferase and is the work-horse of many similar procedures. However, the novel and unique feature of the NanoBiT™ technology is the enzyme is first broken into two parts, which means that in the absence of the immune complex no signal is seen. However, when immune complex is bound, this triggers a specific protein:protein interaction that allows the two parts to recombine to transmit light.”

He adds: “These results are very exciting for preclinical scientists. This new method has numerous potential applications including the monitoring of immune complexes in autoimmune diseases and the study of underlying biology. We hope the screening of larger cohorts of patients will identify a clear clinical application.”

 

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Paper details:
Detection of Experimental and Clinical Immune Complexes by Measuring SHIP-1 Recruitment to the Inhibitory FcγRIIB
Richard J. Stopforth, Robert J. Oldham, Alison L. Tutt, Patrick Duriez, H. T. Claude Chan, Brock F. Binkowski, Chad Zimprich, Dun Li, Philip G.  Hargreaves, Mei Cong, Venkat Reddy, Maria J. Leandro, Geraldine Cambridge, Anja Lux, Falk Nimmerjahn and Mark S. Cragg
doi:10.4049/jimmunol.1700832

 

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