Pulmonary arterial hypertension associated to systemic erythematosus lupus: molecular characterization of 3 cases

Abstract

Background and objective: Pulmonary arterial hypertension associated with systemic lupus erythematosus (PAH-SLE) is a rare disease with a low incidence rate. In this study, PAH related genes and genetic modifiers were characterised molecularly in patients with PAH-SLE.

Patients and methods: Three patients diagnosed with PAH-SLE and 100 control individuals were analysed after signing an informed consent.

Results: Two out of the three analysed patients with PAH-SLE were carriers of pathogenic mutations in the genes BMPR2 and ENG. After an in silico analysis, pathogenic mutations were searched for in control individuals and different databases, with negative results, and they were thus functionally analysed. The third patients only showed polymorphisms in the genes BMPR2, ACVRL1 and ENG. Several genetic variants and genetic modifiers were identified in the three analysed patients. These modifiers, along with the pathogenic mutations, could lead to a more severe clinical course in patients with PAH.

Conclusions: We present, for the first time, patients with PAH-SLE carrying pathogenic mutations in the main genes related to PAH and alterations in the genetic modifiers.

Keywords: Autoimmunity; Autoinmunidad; Genetic modifiers; Hipertensión arterial pulmonar; Lupus eritematoso sistémico; Modificadores genéticos; Mutaciones; Mutations; Pulmonary arterial hypertension; Systemic lupus erythematosus.