Marcadores moleculares, imunológicos e genéticos das reações hansênicas
Carregando...
Data
2009-05-08
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Federal de Goiás
Resumo
Type 1 (T1R) and Type 2 (T2R) leprosy reactions are complications in the clinical
management of leprosy patients because they can lead to neural damage and impairment,
resulting in irreversible deformities and disabilities. This thesis, presented as research
article/manuscript has investigated potential markers for the diagnosis and prognosis of
leprosy reactions.
In the first study, we evaluated a multicentric cohort of leprosy patients with single
skin lesion which is considered the earliest clinical manifestation of the disease. In this
study, at the moment of diagnosis a skin biopsy was collected for histopathology and for
the investigation of Mycobacterium leprae DNA by polymerase chain reaction (ML-PCR).
After diagnosis patients were treated with single dose of Rifampicin, Ofloxacin and
Minocyclin (ROM) and were clinically monitored during 3 years .During follow up,
around 15% of patients developed T1R. In multivariate analysis, age > 40 years and MLPCR
positivity were associated with T1 manifestation.
The second study aimed to identify potential circulating markers associated with
leprosy reactions. Plasma levels of 27 cytokines/chemokines/growth factors were
quantified by multiplex assay. A nested case control study compared the levels of these
factors in leprosy patients with or without T1R and T2R. Leprosy patients were paired by
sex, age group (+/- 5 years) and histopathological classification. Significant differences in
plasma levels of CXCL10 (p=0.004) and IL6 (p=0.013) were observed in patients with
T1R compared with controls without reaction. IL7 levels (p=0.039) and PDGF-BB
(p=0.041) were increased in T2R and marginally significant for IL6 (p=0.05). This
investigation indicated that CXCL10, IL6 and IL7 may represent potential plasma
biomarkers of leprosy reactions.
The third study investigated the influence of single nucleotide polymorphism (SNP)
in the IL6 gene and the development of leprosy reactions. For this purpose a nested case
control study was performed based on a cohort of 409 leprosy patients recruited in Goiânia-GO. After leprosy diagnosis patients were monitored during multidrug therapy
regarding the appearance of leprosy T1R and T2R. Evidences of positive associations were
observed for leprosy T2R and tag SNPs markers- rs 2069832 (p=0.002), rs 2069840
(p=0.027) and rs 2069845 (p=0.044). These IL6 gene tag SNPs capture information of the
whole gene locus. Positive association with T2R was also seen for the functional variant of
IL6 gene- tag SNP rs 1800795 (p=0.005). Additionally, IL6 plasma levels among TR2
patients and controls without reaction correlated with different IL6 genotypes. No
association was observed between IL6 gene variants and leprosy T1R. The description of
genetic predictive factors of leprosy reactions may contribute to the development of
preventive strategies against these leprosy incapacitating events.
Descrição
Palavras-chave
Citação
SOUSA, Ana Lúcia Osório Maroclo de. Molecular markers, genetic and immunological reactions of leprosy. 2009. 121 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Goiás, Goiânia, 2009.