RESUMO
Tropomyosin was reported as an important allergen in Crassostrea angulata and designated as Cra a 1. The localization of the T cell epitopes and the reduction of the immunoreactivity of Cra a 1 are still lacking. In this study, four T cell epitopes were identified by using wild-type Cra a 1 (wtCra a 1)-immunized mouse splenocytes cultured with synthetic peptides. The immunoreactivity was maintained after chemical denaturation treatment, indicating that the linear epitope is an immunodominant epitope of wtCra a 1. Furthermore, the hypoallergenic derivative (mCra a 1) was developed by the deletion of linear B cell epitopes and retention of T cell epitopes. mCra a 1 could stimulate CD4+T cell proliferation and upregulate interleukin-10 secretion. Overall, basophil activation by mCra a 1 was low, but its ability to induce T cell proliferation was retained, suggesting that mCra a 1 may serve as a viable candidate for treating oyster allergy.
Assuntos
Alérgenos , Crassostrea , Epitopos de Linfócito B , Epitopos de Linfócito T , Animais , Camundongos , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/química , Epitopos de Linfócito T/genética , Alérgenos/imunologia , Alérgenos/química , Alérgenos/genética , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/química , Epitopos de Linfócito B/genética , Crassostrea/imunologia , Crassostrea/química , Crassostrea/genética , Tropomiosina/imunologia , Tropomiosina/genética , Tropomiosina/química , Camundongos Endogâmicos BALB C , Feminino , Humanos , Proliferação de Células/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Hipersensibilidade a Frutos do Mar/imunologia , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacosRESUMO
Sarcoplasmic calcium-binding protein (Cra a 4) from Crassostrea angulata belongs to the EF-hand superfamily, and understanding of its structure-allergenicity relationship is still insufficient. In this study, chemical denaturants were used to destroy the structure of Cra a 4, showing that disruption of the structure reduced its IgG-/IgE-binding activity. To explore which critical amino acid site affects the allergenicity of Cra a 4, the mutants were obtained by site-directed mutations in the disulfide bonds site (C97), conformational epitopes (I105, D114), or Ca2+-binding region (D106, D110) and their IgG-/IgE-binding activity was reduced significantly using serological tests. Notably, C97A had the lowest immunoreactivity. In addition, two conformational epitopes of Cra 4 were verified. Meanwhile, the increase of the α-helical content, surface hydrophobicity, and surface electrostatic potential of C97A affected its allergenicity. Overall, the understanding of the structure-allergenicity relationship of Cra a 4 allowed the development of a hypoallergenic mutant.
RESUMO
BACKGROUND: The addition of Rituximab to standard chemotherapy (C) has been reported to improve the end of treatment outcome in non-Hodgkin lymphoma (NHL) patients. Nevertheless, rituximab has been associated with hepatitis B virus reactivation (HBV-R). OBJECTIVES: The aim of this systematic review and meta-analysis is to research the relationship between rituximab and HBV-R. STUDY DESIGN: We searched the commonly used databases both in English and Chinese from November 1997 to June 30, 2012. Meta-analysis was performed in fixed/random-effects models using Review Manager 5.1 and STATA 10.0. Publication bias was examined through Egger's test and Begg's funnel plot. RESULTS: Nine eligible articles were selected in this review (8 studies in English and 1 studies in Chinese), which included 971 adult patients and met all inclusion and exclusion criteria. Of rituximab-associated HBV-R cases reported through case series (n=387), 304 were HBcAb (+)/HBsAg (-) and 83 HBsAg (+). The pooled effect of rituximab-based therapy on HBV-R significantly increased under fixed-effects model [Relative risk (RR) 2.14, 95%CI 1.42-3.22, P=0.0003]. In subgroup analysis, rituximab-associated HBV-R in isolated HBcAb (+) patients remained high, and the RR was 5.52 (95%CI 2.05-14.85, P=0.0007). The RR of HBV-R in NHL patients with HBsAg (+) treated with R-based therapy when compared with the control population was 1.63 by the random-effects model. CONCLUSIONS: Rituximab therapy may increase the risk of developing HBV-R in NHL patients with HBcAb(+).
Assuntos
Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Vírus da Hepatite B/efeitos dos fármacos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Linfoma não Hodgkin/tratamento farmacológico , Ativação Viral/efeitos dos fármacos , Humanos , Medição de Risco , RituximabRESUMO
The human multidrug resistance gene (MDR1, ABCB1) codes for P-glycoprotein (P-gp) that affects the pharmacokinetics of many drugs. MDR1 single nucleotide polymorphisms (SNPs) are associated with drug clearance. Imatinib is a substrate of P-gp-mediated efflux. We investigated the MDR1 T1236C, G 2677T/A, and C3435T polymorphism in 52 patients with chronic myeloid leukemia treated with imatinib. The distribution of MDR1 1236, 2677, or 3435 genotypes was significantly different between the resistance patients and sensitivity patients. The resistance incidence correlated with the number of T alleles at locus 1236 and 3435. Resistance was higher for patients homozygous for the 1236T allele when compared to patients with CT/CC genotype groups (75% vs. 31.3%, P = 0.004). For the G2677T/A polymorphism, a better complete cytogenetic remission was observed for patients with genotype AG/AT/AA, when compared to other genotype groups (TT/GT/GG, P = 0.02). Patients with 3435 TT/CT genotypes showed a higher resistance when compared with patients with CC genotype (59.4% vs. 25%, P = 0.023). In conclusion, determination of 1236T, C3435T, and G2677T MDR1 polymorphisms might be useful in response prediction to therapy with imatinib in patients with CML.