Genes from Chagas Susceptibility Loci That Are Differentially Expressed in T. cruzi-Resistant Mice Are Candidates Accounting for Impaired Immunity

Variation between inbred mice of susceptibility to experimental Trypanosoma cruzi infection has frequently been described, but the immunogenetic background is poorly understood. The outcross of the susceptible parental mouse strains C57BL/6 (B6) and DBA/2 (D2), B6D2F1 (F1) mice, is highly resistant to this parasite. In the present study we show by quantitative PCR that the increase of tissue parasitism during the early phase of infection is comparable up to day 11 between susceptible B6 and resistant F1 mice. A reduction of splenic parasite burdens occurs thereafter in both strains but is comparatively retarded in susceptible mice. Splenic microarchitecture is progressively disrupted with loss of follicles and B lymphocytes in B6 mice, but not in F1 mice. By genotyping of additional backcross offspring we corroborate our earlier findings that susceptibility maps to three loci on Chromosomes 5, 13 and 17. Analysis of gene expression of spleen cells from infected B6 and F1 mice with microarrays identifies about 0.3% of transcripts that are differentially expressed. Assuming that differential susceptibility is mediated by altered gene expression, we propose that the following differentially expressed transcripts from these loci are strong candidates for the observed phenotypic variation: H2-Eα, H2-D1, Ng23, Msh5 and Tubb5 from Chromosome 17; and Cxcl11, Bmp2k and Spp1 from Chromosome 5. Our results indicate that innate mechanisms are not of primary relevance to resistance of F1 mice to T. cruzi infection, and that differential susceptibility to experimental infection with this protozoan pathogen is not paralleled by extensive variation of the transcriptome

Therapeutic plasmapheresis in thyrotoxic patients

WOS: 000445383900017PubMed ID: 29968224Purpose For the treatment of thyrotoxicosis, alternative treatment modalities may be necessary if anti-thyroid drugs cannot be used due to side effects, inefficiencies, or there is a need to start a rapid action such as thyroid storm. By using therapeutic plasma exchange (TPE), it is possible to effectively and rapidly remove the increased thyroid hormones. We evaluated our results and experience on a rapid, effective, and reliable alternative treatment modality in thyrotoxic patients. Methods TPE was performed in 46 thyrotoxic patients at the Adult Therapeutic Apheresis Center. Results Forty six patients with a median age of 30 years (interquartile range [IQR] 30-50) were assessed. In 40 (87%) of the cases, the diagnosis was Graves' disease. The other causes of thyrotoxicosis were amiodarone-induced thyrotoxicosis (n = 4) and toxic nodular goiter (n = 2). The median and IQR of fT3 values in patients before TPE were 9.9 (6.5-16.8) pg/mL (N: 2.3-4.2) and the median and IQR of fT4 values were 2.9 (2.3-4.1) ng/dL (N: 0.74-1.52). When the procedure was terminated, the median and IQR of fT3 values in patients were 4.0 (3.1-5.2) pg/mL and the median and IQR fT4 values were 1.6 (1.4-2.0) ng/dL. The decrease in both free thyroid hormones was found to be statistically significant (p < 0.000). Conclusion Our study is the largest series of TPE in the literature used for thyrotoxicosis. In the light of the literature and our results, we conclude that TPE is an effective alternative treatment option to prepare for ablative treatment for cases that have side effects or ineffectiveness of anti-thyroid drugs