Non-responder Samples Research Articles

Genotypic profiles of Leishmania (Viannia) braziliensis strains from cutaneous leishmaniasis patients and their relationship with the response to meglumine antimoniate treatment: a pilot study.

Background: Forty-four strains isolated from a cohort of cutaneous leishmaniasis (CL) patients who did or did not respond to one course of treatment with meglumine antimoniate were investigated to explore genetic polymorphisms in parasite kinetoplast DNA minicircles. Leishmania (Viannia) braziliensis strains isolated from responder (R) and non-responder (NR) patients who acquired infection in Rio de Janeiro or in other Brazilian states were studied using low-stringency single-specific primer polymerase chain reaction (LSSP-PCR) to identify genetic polymorphisms. Results: Polymorphisms were observed in parasites recovered from patient lesions. No association was found between a specific genotype and R or NR patients. Phenetic analysis grouped the genotypes into three main clusters, with similarity indices varying from 0.72 to 1.00. Although no specific genotype association was detected, at least one group of L. (V.) braziliensis genotypes that circulates in Rio de Janeiro was discriminated in clusters I and III, showing phenotypes of good and poor responses to treatment, respectively. Cluster I comprised parasite profiles recovered from R patients from Rio de Janeiro and in cluster III, NR samples were prevalent. Cluster II comprised 24 isolates, with 21 from Rio de Janeiro and three from other states, equally distributed between R and NR patients. Additionally, we found that parasites sharing all common genetic characteristics acted differently in response to treatment. Conclusions: These results are of clinical-epidemiological importance since they demonstrate that populations of L. (V.) braziliensis that exhibit high levels of genetic similarity also display different phenotypes associated with meglumine antimoniate responses in cutaneous leishmaniasis patients.

Hepatic Gene Expression Discriminates Responders and Nonresponders in Treatment of Chronic Hepatitis C Viral Infection

Pegylated interferon (IFN)-alpha plus ribavirin is the most effective treatment of chronic hepatitis C but has unpleasant side effects and high costs. A large proportion of patients do not respond to therapy for reasons that are unclear. We used gene expression profiling to investigate the molecular basis for treatment failure. Expression profiling was performed on percutaneous needle liver biopsy specimens taken before therapy. Gene expression levels were compared among 15 nonresponder, 16 responder, and 20 normal liver biopsy specimens. Differential gene expression was confirmed using real-time polymerase chain reaction. We identified 18 genes whose expression differed significantly between all responders and all nonresponders (P < .005). Many of these 18 genes are IFN sensitive and 2 (ISG15/USP18) are linked in a novel IFN-regulatory pathway, suggesting a possible rationale for treatment resistance. Using a number of independent classifier analyses, an 8-gene subset accurately predicted treatment response for 30 of 31 patients. The classifier analyses were applicable to patients with genotype 1 infection and were not correlated with viral load, disease activity, or fibrosis. Hepatic gene expression profiling identified consistent differences in patients who subsequently fail treatment with pegylated IFN-alpha plus ribavirin: up-regulation of a specific set of IFN-responsive genes predicts nonresponse to exogenous therapy. These data may be of use in predicting clinical responses to treatment.