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ABSTRACT #26CLINICAL SCIENCESGRADUATE STUDENTPOSTER presentationIncreasing incidence of myasthenia gravis among elderly in British Columbia,Canada: 1984-2011Zahra Pakzad 1,2 , Tariq Aziz 2 , Joel Oger 1,21Department of Pathology and Laboratory Medicine, UBC; 2 Neuroimmunology Laboratory,Division of Neurology, Department of Medicine, UBCBackground /objectivesMyasthenia gravis (MG) is an antibody-mediated autoimmune disease of the neuromuscular junction,characterized by weakness and fatigability of skeletal muscle. The primary antigenic target in MG is the nicotinicacetylcholine receptor (AChR), a ligand-gated sodium channel located at high density on the post-synapticmuscle cell membrane. Anti-AChR antibodies are detected in sera of 80-90% of generalized MG patients and40-70% of patients with ocular MG. Their high specificity makes anti-AChR seropositivity an excellent surrogatemarker for MG. This study aimed to evaluate changes in the incidence and of anti-AChR antibody-seropositiveMG in British Columbia (BC), Canada, between the years of 1984 and 2011.38MethodsThe Neuroimmunology Laboratory at the University of British Columbia is the sole laboratory in BC thatprovides anti-AChR antibody testing for clinical diagnosis. Incident cases of anti-AChR seropositivity wereidentified by retrospectively identifying all first-time cases of anti-AChR antibody-seropositivity in theperiod of January 1984 to December 2011. Incidence was defined as the annual number of first-time anti-AChR seropositive cases. Incidence rates (IRs) were calculated per 1 million inhabitants based on annual Julypopulation estimates (www.bcstats.gov.bc.ca). Cases were stratified into four ages groups based on age at thefirst positive test: ≤19, 20-44, 45-64 and ≥65 years. Age- and sex-stratified IRs were calculated using populationestimates of the corresponding age and sex group.ResultsBetween January 1984 and December 2011, 1493 individuals were identified to be anti-AChR antibodyseropositive(767 women, 718 men, 8 unknown). In women the age at the first positive serum sample had abimodal distribution with peaks at 45-55 and 70-85 years, while in men there was a single peak at 70-80 years.The annual incidence of new AChR seropositivity has increased from 11.0/million (1984-1988 average) to 16.7/million (2007-2011 average). The incidence has most dramatically increased in the elderly (≥65 years), from 21.4/million (1984-1988 average) to 61.9/million (2007-2011 average). In contrast, the mean annual IRs of the threeyounger age groups has remained relatively constant over the 28-year period. These results confirm that the trendwe had described in an earlier report, of increasing incidence of elderly-onset anti-AChR seropositive MG in BCfor the period of 1984-2008, is continuing (Pakzad Z et al., Neurology 2011).ConclusionsOur results indicate a continually increasing incidence of elderly-onset anti-AChR seropositive MG in BC which isnot due to demographic changes. This trend could be due to improved diagnosis of MG in elderly patients over thedecades, or a true increase in the incidence due to as yet undefined reasons.2012 * Oral/Poster Presentations
POSTER presentationRESIDENTCLINICAL SCIENCESABSTRACT #27Regulatory T cells in CNS inflammationFahad A Alghamdi 1 , Wayne Moore 1 , Katerina Dorovini-Zis 11University of British Columbia and Vancouver General HospitalBackground /objectivesRegulatory T cells (Tregs) are thymus-derived CD4+ CD25+T lymphocytes that play an important role inmaintenance of self-tolerance and suppression of autoimmunity. Tregs recognize both self and foreign antigensand operate at sites of inflammation by suppressing the function of effector T cells, thus modulating theintensity and quality of immune responses. Their identification is based on the expression of activation markersand the forkhead transcription factor P3 (Foxp3). The contribution of Tregs to CNS inflammatory diseases hasnot been previously addressed.MethodsWe investigated the presence and distribution of Tregs in cases of multiple sclerosis (MS), primary CNS angiitis,sarcoidosis, bacterial, viral and parasitic infections, acute infarction and normal brain. Formalin fixed, paraffinembedded sections of surgical and autopsy material were stained with the indirect immunoperoxidase techniqueusing monoclonal anti-Foxp3, CD4 and CD8 antibodies.ResultsCD4+Foxp3+Tregs were present within the perivascular chronic inflammatory infiltrates in primary CNSangiitis and active MS lesions, but not in chronic inactive MS plaques. In sarcoidosis, tuberculosis, viralinfections and abscesses, frequent Tregs were identified in perivascular location and scattered in the inflamedtissue. A smaller number were present in parasitic and fungal infections and in leptomeningeal exudates inbacterial meningitis. Tregs were absent in the normal brain and acute ischemic lesions.ConclusionsThe present study shows participation of Tregs in autoimmune and infectious diseases suggesting a compleximmune regulatory role in CNS inflammation.Oral/Poster Presentations * 2012 39
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