RESUMO
BACKGROUND Leprosy or hansen’s disease is a spectral disease whose clinical forms mostly depends on host’s immune and genetic factors. Different Toll-like receptors (TLR) variants have been described associated with leprosy, but with some lack of replication across different populations. OBJECTIVES To evaluate the role of polymorphisms in genes TLR1, TLR2 and TLR4 and susceptibility to leprosy in a genetic case control study; to verify the association between genotypes of these markers and the immunological profile in the serum of patients with leprosy. METHODS Pre-designed TaqMan® assays were used to genotype markers at TLR1 (rs4833095, rs5743551), TLR2 (rs7656411, rs3804099) and TLR4 (rs1927914, rs1927911). A panel of cytokines and chemokines was accessed by enzime-linked immunosorbent assay (ELISA) test in the serum of a subgroup of patients with and without leprosy reactions. FINDINGS Our results show an association between the T allele of rs3804099 at the TLR2 gene and increased risk for leprosy per se [Odds ratio (OR) = 1.296, p = 0,022]. In addition, evaluating the association between different genotypes of the TLR1, 2 and 4 markers and cytokine/chemokine serological levels, IL-17 appears as an immunological marker regulated by the polymorphism of the three TLR genes evaluated, whereas different TLR1 genotypes were associated with differential production of IL-12p40 and MCP-1(CCL2). Furthermore, other relevant serum markers such as CXCL-10 and IL-6 seemed to be regulated by TLR2 variants and IL-1β was related to TLR4 genotypes. MAIN CONCLUSIONS All together our data points that the tested TLR markers may have a regulatory role in the immunity against Mycobacterium leprae, by driving the host’s production of key cytokines and chemokines involved in the pathogenesis of this disease.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Quimiocinas/imunologia , Quimiocinas/sangue , Receptor 1 Toll-Like/genética , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Hanseníase/genética , Hanseníase/imunologia , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo Único , Alelos , ELISPOT , GenótipoRESUMO
Snake antivenom, an expensive animal product, is presently the only effective treatment for the consequences of snakebite. In Latin America, antivenoms are mainly produced by public institutions with frequent shortages of the necessary supply. Here, we present an economical analysis of the factors affecting production cost, assuming a basic processing batch of 100 L hyperimmune plasma. Three annual production volumes were considered for two typical production technologies. The components of cost were classified as fixed, variable and semi-variable. We found that in all stages of production, fixed cost represents the major contribution to total cost, and is given essentially by manpower cost, particularly for low production volumes. Our estimation shows that antivenom cost can vary from US$ 2.4 to US$ 25 per 10 mL vial, depending on the production volume, the plasma processing technology used and the titer achieved during the immunization stage. We conclude that interested laboratories and authorities of countries with population at risk should consider the possibility of a joint production to improve the process efficiency, lower the product unitary cost and obtain the necessary supply for their own demand or that of other countries in need.
RESUMO
ELISA was used to evaluate, accompany, and compare the humoral immune response of Swiss mice during hyperimmunization with native and Cobalt-60-irradiated (60Co) venoms of Bothrops jararaca, Bothrops jararacussu and Bothrops moojeni. Potency and neutralization were evaluated by in vitro challenges. After hyperimmunization, immunity was observed by in vivo challenge, and the side effects were assessed. The animals immunization with one LD50 of each venom occurred on days 1, 15, 21, 30, and 45, when blood samples were collected; challenges happened on the 60th day. Results showed that ELISA was efficient in evaluating, accompanying and comparing mouse immune response during hyperimmunization. Serum titers produced with natural venom were similar to those produced with irradiated venom. Immunogenic capacity was maintained after 60Co-irradiation. The sera produced with native venom showed neutralizing potency and capacity similar to those of the sera produced with irradiated venom. All antibodies were able to neutralize five LD50 from these venoms. Clinical alterations were minimum during hyperimmunization with irradiated venom, however, necrosis and death occurred in animals inoculated with native venom.