Marianna M. Newkirk
Associate Professor; Medicine
Etiology of autoimmune rheumatic diseases: Role of antigen, antibody and anti-inflammatory proteins
Accepting graduate students
Department of Rheumatology
Montreal General Hospital
1650 Cedar Ave.
Montreal, QC H3G 1A4
Tel: (514) 934-1934 x.44075
Fax: (514) 934-8239
marianna [dot] newkirk [at] mcgill [dot] ca (Email)
Circulating in patients with rheumatoid arthritis (RA) are two types of autoantibodies: rheumatoid factors (RF) which bind to the Fc portion of IgG, and antibodies that bind to advanced glycation end products on IgG (AGE) as a linked immune response. AGEs are the result of a process of non-enzymatic glycation, which occurs in the presence of high blood glucose and oxidative stress. Antibodies to IgG-AGE are associated with active and disabling disease and are elevated in some tribes of North American Indians. We are interested in leaning more about the pathogenesis of IgG-AGE and the immune response against it in patients with RA. Another group of antibodies linked to the RF response in patients with RA are antibodies against Proteus mirabilis. We are currently characterizing a P. mirabilis glycoprotein, which can induce RFs in vitro and in vivo.
The RF response is also detected in patients infected with Hepatitis C virus. The RF complex with the anti-viral IgG, and form what is known as mixed cryoglobulins. These immune complexes are a feature of severe liver disease, and contribute to the extra hepatic manifestations of the disease. Current studies in the laboratory are investigating the impact of liver disease on the generation of RF in an animal model in order to better understand their pathophysiology.
Systemic Lupus Erythematosus:
Viral infections have long been suspected to play a role in autoimmune disease. We are investigating the interrelationship between cytomegalovirus (CMV) infection and the autoimmune response to the spliceosome complex, which occurs in both man and mouse. The spliceosome is the target of autoantibodies in patients with Systemic Lupus Erythematosus (SLE). Interestingly some strains of mice mount a vigorous autoimmune response to a CMV vaccine based on the glycoprotein gB and they develop a disease similar to SLE, whereas others do not. By studying animal models, we hope to learn more about the pathological events that can lead to autoimmunity after viral infection and the genes involved in this autoimmune response.
Selected Recent Publications
Newkirk MM. Rheumatoid factors: host resistance or autoimmunity? Clin Immunol. 2002;104(1):1-13.
Lipes J, Skamene E, Newkirk MM. The genotype of mice influences the autoimmune response to spliceosome proteins induced by cytomegalovirus gB immunization. Clin Exp Immunol 2002; 129(1):19-26.
Newkirk MM, van Venrooij WJ, Marshall GS Autoimmune response to U1 small nuclear ribonucleoprotein (U1 snRNP) associated with cytomegalovirus infection. Arthritis Res. 2001;3(4):253-8.
Tai AW, Newkirk MM An autoantibody targeting glycated IgG is associated with elevated serum immune complexes in rheumatoid arthritis (RA). Clin Exp Immunol. 2000 Apr;120(1):188-93.
Lucey MD, Newkirk MM, Neville C, Lepage K, Fortin PR Association between IgM response to IgG damaged by glyoxidation and disease activity in rheumatoid arthritis. J Rheumatol. 2000 Feb;27(2):319-23.