ABSTRACT
Systemic lupus erythematosus (SLE) involves a florid set of clinical manifestations whose autoreactive origin is characterized by an overactivation of the immune system and the production of a large number of autoantibodies. Because it is a complex pathology with an inflammatory component, its pathogenesis is not yet fully understood, assuming both genetic and environmental predisposing factors. Currently, it is known that the role of the human microbiome is crucial in maintaining the transkingdom balance between commensal microorganisms and the immune system. In the present work we study the intestinal microbiota of Argentine patients with different stages of SLE receiving or not different treatments. Microbiota composition and fecal miRNAs were assessed by 16â¯S sequencing and qPCR. hsa-miR-223-3p, a miRNA involved in several inflammation regulation pathways, was found underexpressed in SLE patients without immunosuppressive treatment. In terms of microbiota there were clear differences in population structure (Weighted and Unweighted Unifrac distances, p-value <0.05) and core microbiome between cases and controls. In addition, Collinsella, Bifidobacterium, Streptococcus genera and aromatics degradation metabolisms were overrepresented in the SLE group. Medical treatment was also determinant as several microbial metabolic pathways were influenced by immunosuppressive therapy. Particularly, allantoin degradation metabolism was differentially expressed in the group of patients receiving immunosuppressants. Finally, we performed a logistic regression model (LASSO: least absolute shrinkage and selection operator) considering the expression levels of the fecal hsa-miR223-3p; the core microbiota; the differentially abundant bacterial taxa and the differentially abundant metabolic pathways (p<0.05). The model predicted that SLE patients could be associated with greater relative abundance of the formaldehyde oxidation pathway (RUMP_PWY). On the contrary, the preponderance of the ketodeoxyoctonate (Kdo) biosynthesis and activation route (PWY_1269) and the genera Lachnospiraceae_UCG_004, Lachnospira, Victivallis and UCG_003 (genus belonging to the family Oscillospiraceae of the class Clostridia) were associated with a control phenotype. Overall, the present work could contribute to the development of integral diagnostic tools for the comprehensive phenotyping of patients with SLE. In this sense, studying the commensal microbial profile and possible pathobionts associated with SLE in our population proposes more effective and precise strategies to explore possible treatments based on the microbiota of SLE patients.
Subject(s)
Biomarkers , Feces , Gastrointestinal Microbiome , Lupus Erythematosus, Systemic , MicroRNAs , Humans , MicroRNAs/genetics , Lupus Erythematosus, Systemic/microbiology , Lupus Erythematosus, Systemic/immunology , Feces/microbiology , Female , Adult , Biomarkers/metabolism , Male , Middle Aged , Immunosuppressive Agents/therapeutic useABSTRACT
Introducción: La nefritis es la más frecuente de las manifestaciones graves del LES. La respuesta de las formas proliferativas a la inmunosupresión no es uniforme y son frecuentes las exacerbaciones durante o después de finalizado el tratamiento. Métodos: Analizamos retrospectivamente la evolución de una cohorte de 84 pacientes con nefritis lúpica proliferativa con tratamiento inmunosupresor, en un seguimiento prolongado de hasta 203 meses. Se tomaron como basales: Sexo, edad, latencia entre diagnóstico de LES e inicio de nefritis, complemento sérico, creatinina plasmática y proteinuria. Evaluamos: respuesta inicial al tratamiento, aparición de recaída o recidiva y resultado al final del periodo de observación. Resultados: Se produjo remisión inicial en el 73% de los casos, aunque al final del seguimiento, se encontraban en remisión sólo el 54% de los pacientes. 45 pacientes tuvieron un episodio de nefritis, 32 pacientes dos y 7 pacientes tres. La mayoría de las remisiones se produjeron durante la fase de mantenimiento. La remisión completa tuvo mejor evolución que la remisión parcial. La creatininemia y proteinuria elevadas al inicio fueron marcadores de mal pronóstico. La azatioprina resultó más efectiva que la ciclofosfamida como terapia de mantenimiento, aunque presentó una frecuencia elevada de recaídas. El micofenolato no resultó mejor que la ciclofosfamida/ azatioprina en el tratamiento de las recaídas o recidivas. Conclusiones: Nuestros resultados son Asimilares a los de la literatura. El seguimiento prolongado permite evaluar el resultado a largo plazo del cuadro inicial, los posibles brotes posteriores, la efectividad del tratamiento y la evolución tras su interrupción.
Background: Nephritis is the most common of all serious manifestations of SLE. The proliferative forms require immunosuppressive treatment, but responses are not consistent and exacerbations are frequent during or after the treatment has been completed. Methods: We retrospectively analyzed the evolution of a cohort of 84 patients with proliferative lupus nephritis with immunosuppressive treatment, in a long-term (up to 203 months) follow up. Were taken as basal: sex, age, latency between onset and diagnosis of SLE nephritis, serum complement, plasmatic creatinine and proteinuria. We evaluated: initial response to therapy, occurrence of relapse or recurrence and score at the end of the observation period. Results: Remission of initial nephritis was seen in 73% of the cases, although at the end of monitoring only 54% of patients were in remission. 45 patients had one episode of nephritis, 32 patients had two, and 7 patients had three. Most of the remissions took place during the maintenance period. Complete remission had better evolution than partial remission. High serum creatinine levels and proteinuria at baseline were indicators of bad prognosis. Oral Azathioprine was more effective than quarterly IV Cylophosphamide as maintenance therapy, despite of a high incidence of relapses. Mycophenolate was not more effective than Cyclophosphamide/ azathioprine for the treatment of relapses or recurrences. Conclusions: Our results are similar to the literature. Extended follow up enables the evaluation of the long term result of the initial symptoms, any possible future outbreaks, the effectiveness of the treatment and its evolution after its interruption.
