Professor of Experimental Immunology
Rizgar Mageed first qualified from the College of Pharmacy at Baghdad University in 1976. He was awarded his PhD at the Royal London Hospital Medical School, London University in 1985. He was appointed Research Fellow at the Department of Immunology University of Birmingham Medical School in 1984 where he worked until 1990 and then joined the Kennedy Institute of Rheumatology as a Senior Scientist. In 1996, Rizgar was appointed Senior Lecturer at Imperial College. In 2000, Rizgar was awarded Arthritis Research-UK Fellowship and appointed Senior Lecturer at the Centre for Rheumatology at University College London. Rizgar joined Queen Mary University of London in May 2003. In 2009 Rizgar become a fellow of the Royal College of Pathologists (FRCPath) and in 2014 was awarded his fellowship by the Royal College of Physicians (FRCP).
Summary of Research
Bone and Joint Research Unit
Our studies are focussed on defining the molecular basis of humoral autoimmunity in patients with rheumatic diseases. These studies explore how abnormalities in intracellular signaling pathways in lymphocytes promote hyperactivity and autoimmunity. Recent studies have identified defects in key intracellular pathways in B-lymphocytes in patients with systemic lupus erythematosus (SLE). These studies showed enhanced activation of signaling pathways linked with the B-cell receptor (BCR) and the PI-3 kinase. The effect of treating SLE patients with B-lymphocyte depleting antibodies on signaling defects is also being examined. Other studies examine how biological anti-TNF? therapies modulate the immune system in patients with rheumatoid arthritis (RA). These studies show that treatment with biological anti-TNF? agents influence humoral and cellular immunity and promote the expansion of T-helper 17 (TH17) lymphocytes. Excess activation of TH17 cells results in incomplete responsiveness of patients to anti-TNF? therapy. Most recent experiments aim to explore these discoveries to develop therapies that selectively target proteins and signaling pathways in lymphocytes from patients with autoimmune diseases. In this regard, we have developed and are assessing recombinant single chain variable regions (scFv) of antibodies and small molecular inhibitors to deliver inhibitors of defective signaling pathways.
B-lymphocytes in patients with SLE have reduced level of signalling molecules that help regulate cellular functions. (A) Confocal microscopy depicting reduced Lyn level and translocation to lipid raft signalling microdomains in SLE B-lymphocytes compared with a healthy individual. Translocation of Lyn (green) into lipid raft microdomains (red) is indicated by yellow patches from merging the green and red colours. The abnormality in Lyn expression is associated with increased CD45 translocation to lipid raft signalling microdomains (B). Other molecules that partake in regulating Lyn, such as Csk (C), and c-Cbl (D) are not affected. [Scale bar in red lines= 5µm). Quantification of signalling molecule translocation shows an inverse relationship between Lyn and CD45 (E and F).
Members of the Group
Research fellows: Dr. T. E. Taher; Dr. J. Bystrom;
PhD students: Miss N. Nordin; Mr. M. Albogami; Mr. H. Muhammad; Dr. G. Mittal.
For a full list of publist publications click here
Alzabin S, Abraham SM, Taher TE, Palfreeman A, Hull D, McNamee K, Jawad A, Pathan E, Kinderlerer A, Taylor PC, Williams R, Mageed R. Incomplete response of inflammatory arthritis to TNFα blockade is associated with the Th17 pathway. Ann Rheum Dis. 2012 May 1.
Thabet Y, Cañas F, Ghedira I, Youinou P, Mageed RA, Renaudineau Y. Altered patterns of epigenetic changes in systemic lupus erythematosus and auto-antibody production: Is there a link? J Autoimmun. 2012 Jun 16. [Epub ahead of print]
Mageed RA, Garaud S, Taher TE, Parikh K, Pers JO, Jamin C, Renaudineau Y, Youinou P. CD5 expression promotes multiple intracellular signaling pathways in B lymphocyte. Autoimmun Rev. 2012 Feb 12.
Garaud S, Morva A, Lemoine S, Hillion S, Bordron A, Pers JO, Berthou C, Mageed RA, Renaudineau Y, Youinou P. CD5 promotes IL-10 production in chronic lymphocytic leukemia B cells through STAT3 and NFAT2 activation. J Immunol. 2011; 186: 4835-44.
Séïté JF, Cornec D, Renaudineau Y, Youinou P, Mageed RA, Hillion S. IVIg modulates BCR signaling through CD22 and promotes apoptosis in mature human B lymphocytes. Blood. 2010 Sep 9;116(10):1698-704.
Taher TE, Parikh K, Flores-Borja F, Mletzko S, Isenberg DA, Peppelenbosch MP, Mageed RA. Protein phosphorylation and kinome profiling reveal altered regulation of multiple signaling pathways in B lymphocytes from patients with systemic lupus erythematosus. Arthritis Rheum 2010; 62: 2412-23.
Youinou P, Taher TE, Pers JO, Mageed RA, Renaudineau Y. B lymphocyte cytokines and rheumatic autoimmune disease. Arthritis Rheum 2009; 60: 1873-80.
Rochas C, Hillion S, Saraux A, Mageed RA, Youinou P, Jamin C, Devauchelle V. Transmembrane BAFF from rheumatoid synoviocytes requires interleukin-6 to induce the expression of recombination-activating gene in B lymphocytes. Arthritis Rheum 2009; 60: 1261-71.
Garaud S, Le Dantec C, Jousse-Joulin S, Hanrotel-Saliou C, Saraux A, Mageed RA, Youinou P, Renaudineau Y. IL-6 modulates CD5 expression in B cells from patients with lupus by regulating DNA methylation. J Immunol 2009; 182: 5623-32.