RESUMO
BACKGROUND: In the pre-microbiological era, it was widely accepted that diseases, today known to be infectious, were hereditary. With the discovery of microorganisms and their role in the pathogenesis of several diseases, it was suggested that exposure to the pathogen was enough to explain infection. Nowadays, it is clear that infection is the result of a complex interplay between pathogen and host, therefore dependant on the genetic make-up of the two organisms. Dermatology offers several examples of infectious diseases in different stages of understanding of their molecular basis. In this review, we summarize the main advances towards dissecting the genetic component controlling human susceptibility to infectious diseases of interest in dermatology. Widely investigated diseases such as leprosy and leishmaniasis are discussed from the genetic perspective of both host and pathogen. Others, such as rare mycobacterioses, fungal infections and syphilis, are presented as good opportunities for research in the field of genetics of infection.
Assuntos
Predisposição Genética para Doença/genética , Interações Hospedeiro-Patógeno/genética , Dermatopatias Infecciosas/genética , Histoplasmose/genética , Humanos , Leishmania/genética , Leishmaniose/genética , Hanseníase/genética , Mycobacterium leprae/genética , Paracoccidioidomicose/genética , Fatores de Risco , Sífilis Cutânea/genética , Tuberculose Cutânea/genéticaRESUMO
BACKGROUND: In the pre-microbiological era, it was widely accepted that diseases, today known to be infectious, were hereditary. With the discovery of microorganisms and their role in the pathogenesis of several diseases, it was suggested that exposure to the pathogen was enough to explain infection. Nowadays, it is clear that infection is the result of a complex interplay between pathogen and host, therefore dependant on the genetic make-up of the two organisms. Dermatology offers several examples of infectious diseases in different stages of understanding of their molecular basis. In this review, we summarize the main advances towards dissecting the genetic component controlling human susceptibility to infectious diseases of interest in dermatology. Widely investigated diseases such as leprosy and leishmaniasis are discussed from the genetic perspective of both host and pathogen. Others, such as rare mycobacterioses, fungal infections and syphilis, are presented as good opportunities for research in the field of genetics of infection.
INTRODUÇÃO: Durante a era pré-microbiológica, era comum a visão de que doenças, hoje sabidamente infecciosas, eram hereditárias. Com a descoberta dos microorganismos e seu papel na patogênese de diversas patologias, chegou-se a propor que a exposição ao patógeno era condição suficiente para explicar infecção. Hoje, está claro que infecção é o resultado de uma complexa interação entre patógeno e hospedeiro, dependendo portanto, em última análise, do make-up genético de ambos os organismos. A dermatologia oferece diversos exemplos de doenças infecciosas em diferentes graus de entendimento de suas bases moleculares. Nesta revisão, resumimos os principais avanços na direção da dissecção do componente genético controlando suscetibilidade do ser humano a doenças infecciosas de importância na dermatologia. Doenças amplamente estudadas, como a hanseníase e a leishmaniose, são discutidas sob o ponto de vista da genética tanto do hospedeiro quanto do patógeno. Outras, como micobacterioses raras, micoses e sífilis, são apresentadas como boas oportunidades para pesquisa na área de genética de infecção.
Assuntos
Humanos , Predisposição Genética para Doença/genética , Interações Hospedeiro-Patógeno/genética , Dermatopatias Infecciosas/genética , Histoplasmose/genética , Leishmania/genética , Leishmaniose/genética , Hanseníase/genética , Mycobacterium leprae/genética , Paracoccidioidomicose/genética , Fatores de Risco , Sífilis Cutânea/genética , Tuberculose Cutânea/genéticaRESUMO
Families with multiple cases of leprosy were tested for HLA (histocompatibility leukocyte antigen)-linked control of susceptibility to tuberculoid leprosy and association with HLA-DR2. Thirty-one non-HLA genetic markers were also examined for indications of non-HLA-linked genetic factors that might control susceptibility to tuberculoid leprosy. A significant (P = 0.002) preferential inheritance of HLA-DR2 by siblings affected with tuberculoid leprosy, but not by healthy siblings nor by siblings affected with lepromatous leprosy, was observed. In addition, combined family data showed a significant (P less than 0.0025) excess of identical HLA haplotypes inherited from healthy parents by siblings affected with tuberculoid leprosy. Segregation on non-HLA polymorphisms did not deviate significantly from what would have occured randomly. These data are compatible with a recessive inheritance of HLA-linked susceptibility to tuberculoid leprosy. The preferential segregation of DR2 observed in children with tuberculoid leprosy (P less than 0.001 for the combined data from India) indicates that the HLA-linked susceptibility gene is either DR2 or in linkage disequilibrium with it.