Quinnell et al 2003 ppt

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Published on November 16, 2007

Author: lusi

Source: authorstream.com

Susceptibility to visceral leishmaniasis in domestic dog is associated with MHC class II polymorphism:  Susceptibility to visceral leishmaniasis in domestic dog is associated with MHC class II polymorphism By: Rupert J. Quinnell, Lorna Kennedy, et al. Presented by Alicia Martin What is visceral leishmaniasis?:  What is visceral leishmaniasis? Zoonotic disease Caused by Leishmania infantum Occurs in Mediterranean and parts of Asia, Africa, and Latin America Passed by phebotomine sandflies L. Infantum in dogs:  L. Infantum in dogs Outcome of infection is variable Mount humoral and cellular response Protective immunity Interleukin-2 tumor necrosis factor Antibody response not protective Factors for variation in clinical outcome Objectives :  Objectives Describe the distribution of DLA-DRB1, -DQA1, and –DQB1 in study population Study the effect of non-DLA variables on outcome of infection Examine the relationship between DLA class II alleles and the course of the infection Experimental Setup:  Experimental Setup 99 uninfected dogs from Belen 27 serologically negative from Marajo Eight cohorts with 5-37 dogs Sampled at mean intervals of 67.3 days First sample from dog with evidence of infection by PCR, parasite culture, or serology Paristology, clinical examination, and immunology:  Paristology, clinical examination, and immunology Parasite DNA detected by PCR Scored for six symptoms of VL: alopecia, dermatitis, cutaneous ulceration, conjuctivis, onychogryphosis, and popliteal lymphadenopathy Antibody and lymphoproliferative response to Leishmania antigen DLA-DRB1, DQAI, & DQB1 allele assignment:  DLA-DRB1, DQAI, & DQB1 allele assignment DNA extracted from bone marrow biopsies or peripheral blood mononuclear cells Samples characterized sequence-based typing Statistical Analysis:  Statistical Analysis T4 statistic from CLUMP program used to detect differences in allele frequencies Multiple regression used to analyze VL phenotypes Results:  Results Genotype frequencies did not differ from Hardy-Weinberg equilibrium Significant difference in allele frequencies between dogs from Belem and Marajo No relationship between age of dog at infection or sex and infection phenotypes Significant relationship between dog origin and anti-Leishmania IgG response Frequencies of DLA-DRB1, -DQA1, and DQB1 alleles:  Frequencies of DLA-DRB1, -DQA1, and DQB1 alleles Stepwise Multiple Regression Analysis:  Stepwise Multiple Regression Analysis Results:  Results Significant relationship between DLA-DRB1 genotype and both anti-Leishmania IgG level and parasite detection by PCR DLA-DRB1*01502 allele An association between DLA-DQA1 and anti-Leishmania cellular response, but not significant Anti-Leishmania IgG levels (a) & Proportion of positive dogs (b):  Anti-Leishmania IgG levels (a) & Proportion of positive dogs (b) Conclusion:  Conclusion There is significant association between DLA-DBR1 and susceptibility to visceral leishmaniasis in dogs Goal:  Goal To make a vaccine that is effective in all breeds and genotypes Analysis of Paper:  Analysis of Paper Important topic Materials & Methods could have been expanded Background information effective Discussion very well structured

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