Multiple Sclersosis (MS) is an inflammatory, demyelinating disease of the Central Nervous System (CNS) which likely involves an autoimmune mechanism directed agains self-myelin associated antigens. There is substantial evidence suggesting that B cells are involved in the pathogenesis of MS. In order to define the Ig repertoires in the CSF of MS patients and identify Ig’s from clonally expanded B cells using Single Cell PCR. We then plan to explore the antigenic specificity of these unique Ig rearrangements by cloning both the heavy and light chain segments into an expression vector, isolating the resultant Fab fragments, and testing them for their antigenic specificity. We can also use PCR to track the persistence of these clones in the CSF of these original MS patients and determine whether we can detect these clones in their peripheral blood as well as in other MS patients. These studies are necessary in order to directly ascertain the potential role of B cells in the pathogenicity of MS, and ultimately will allow us to explore the possibility of generating specific immunotherapies directed against these clonally expanded B cells in the future.
RESEARCH INTERESTS
Multiple Sclerosis
B cell Biology
Autoimmune Disease
Translational Research
Antibodies
RECENT PUBLICATIONS
37. Stuve O, Marra CM, Cravens PD, Singh MP, Hu W, Lovett-Racke A, Monson NL, Phillips JT, Tervaert JW, Nash RA, Hartung HP, Kieseier BC, Racke MM, Frohman EM, Hemmer B., "Potential risk of progressive multifocal leukoencephalopathy with natalizumab therapy: possible interventions" Arch Neurol, 64:169-76, 2007
36. Harp C., Lee J., Lambracht-Washington D., Frohman E., Racke M.K., and Monson NL, "Cerebrospinal fluid B cells from Multiple Sclerosis patients are subject to normal germinal center selection" J Neuroimmunol, 183:189, 2007
35. Lambracht-Washington D., O?Connor K.C., Jowdry A., Ward E.S., Rula K., Frohman E., Racke M.K., and Monson NL, "Antigen Specificity of Clonally Expanded and Receptor Edited Cerebrospinal Fluid B cells from Patients with Relapsing Remitting MS" J. Neuroimmunol, 186:164-176, 2007
Martin, Maria del Pilar and Monson NL, "Potential Role of Humoral Immunity in the Pathogenesis of Multiple Sclerosis (MS) and Experimental Autoimmune Encephalomyelitis (EAE)" Frontiers in Bioscience, 12:735-2749, 2007
33. Stuve O, Marra C, Bar-Or A, Niino M, Cravens PD, Cepok S, Frohman EM, Phillips JT, Arendt G, Jerome KR, Cook L, Gran?Maison F, Hemmer B, Monson NL, Racke MK, "Altered CD4:CD8 T cell Ratios in Cerebrospinal fluid of Natalizumab treated Multiple Sclerosis Patients" Archives of Neurology, 63:1383-1387, 2006
SIGNIFICANT PUBLICATIONS
32. Stuve O, Marra C, Jerome K, Cook L, Cravens PD, Cepok S, Frohman EM, Phillips JT, Arendt G, Hemmer B, Monson NL and Racke MK, "Immune Surveillance in Multiple Sclerosis Patients Treated with Natalizumab" Ann Neurol, 59:743-747, 2006
Paula S, Monson NL, Ball WJ, Jr, "Molecular Modeling of Cardiac Glycoside Binding by the Monoclonal Human Sequence Antibody 1B3" Proteins, 60:382-391, 2005
30. Frohman EM, Filippi M, Stuve O, Waxman SG, Corboy J, Phillips JT, Lucchinetti C, Wilken J, Karandikar N, Hemmer B, Monson N, De Keyser J, Hartung H, Steinman L, Oksenberg JR, Cree BA, Hauser S, Racke MK., "Characterizing the mechanisms of progression in multiple sclerosis: evidence and new hypotheses for future directions" Arch Neurol, 62(9):1345-56, 2005
29. Monson NL, Cravens PD, Frohman EM, Hawker K, Racke MK, "Effect of rituximab on the peripheral blood and cerebrospinal fluid B cells in patients with primary progressive multiple sclerosis" Arch Neurol, 62:258-64, 2005
28. Monson NL, Brezinschek HP, Brezinschek RI, Mobley A, Vaughan GK, Frohman EM, Racke MK, Lipsky PE, "Receptor revision and atypical mutational characteristics in clonally expanded B cells from the cerebrospinal fluid of recently diagnosed multiple sclerosis patients" J Neuroimmunol, 158:170-81, 2005
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