Background Systemic lupus erythematosus is a heterogeneous chronic inflammatory autoimmune disorder characterized by an exacerbated expression of cytokines and chemokines in different tissues and organs. Renal involvement is a significant contributor to the morbidity and mortality of systemic lupus erythematosus, and its diagnosis is based on renal biopsy, an invasive procedure with a high risk of complications. Therefore, the development of alternative, non-invasive diagnostic tests for kidney disease in patients with systemic lupus erythematosus is a priority. Aim To evaluate the plasma levels of a panel of cytokines and chemokines using multiplex xMAP technology in a cohort of Colombian patients with active and inactive systemic lupus erythematosus, and to evaluate their potential as biomarkers of renal involvement. Results Plasma from 40 systemic lupus erythematosus non-nephritis patients and 80 lupus nephritis patients with different levels of renal involvement were analyzed for 39 cytokines using Luminex xMAP technology. Lupus nephritis patients had significantly increased plasma eotaxin, TNF-α, interleukin-17-α, interleukin-10, and interleukin-15 as compared to the systemic lupus erythematosus non-nephritis group. Macrophage-derived chemokine, growth regulated oncogene alpha, and epidermal growth factor were significantly elevated in systemic lupus erythematosus non-nephritis patients when compared to lupus nephritis individuals. Plasma eotaxin levels allowed a discrimination between systemic lupus erythematosus non-nephritis and lupus nephritis patients, for which we performed a receiver operating characteristic curve to confirm. We observed a correlation of eotaxin levels with active nephritis (Systemic Lupus Erythematosus Disease Activity Index). Our data indicate that circulating cytokines and chemokines could be considered good predictors of renal involvement in individuals with systemic lupus erythematosus.

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The flagellum of Trypanosomatids is an organelle that contributes to multiple functions, including motility, cell division, and host–pathogen interaction. Trypanin was first described in Trypanosoma brucei and is part of the dynein regulatory complex. TbTrypanin knockdown parasites showed motility defects in procyclic forms; however, silencing in bloodstream forms was lethal. Since TbTrypanin mutants show drastic phenotypic changes in mammalian stages, we decided to evaluate if the Trypanosoma cruzi ortholog plays a similar role by using the CRISPR-Cas9 system to generate null mutants. A ribonucleoprotein complex of SaCas9 and sgRNA plus donor oligonucleotide were used to edit both alleles of TcTrypanin without any selectable marker. TcTrypanin −/− epimastigotes showed a lower growth rate, partially detached flagella, normal numbers of nuclei and kinetoplasts, and motility defects such as reduced displacement and speed and increased tumbling propensity. The epimastigote mutant also showed decreased efficiency of in-vitro metacyclogenesis. Mutant parasites were able to complete the entire life cycle in vitro; however, they showed a reduction in their infection capacity compared with WT and addback cultures. Our data show that T. cruzi life cycle stages have differing sensitivities to TcTrypanin deletion. In conclusion, additional work is needed to dissect the motility components of T. cruzi and to identify essential molecules for mammalian stages.

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