Identification of potential biomarkers for systemic lupus erythematosus diagnosis using two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease of the connective tissue with a large spectrum of clinical manifestations. Immune deregulation leads to autoantibody and immune complexes overproduction, complement activation, and persistent tissue inflammation. Considering that the current diagnosis depends on the interpretation of the complex criteria established by the American College of Rheumatology and that the disease course is characterized by unpredictable activations and remissions, each patient develops different manifestations, and therefore, the discovery of specific biomarkers is urgently required. Therefore, this study aimed to identify putative biomarkers for active and inactive SLE potentially capable in distinguishing laboratorial SLE from other autoimmune diseases. The 2D-DIGE proteomics technique was used to evaluate the differential abundance of proteins between patients with active SLE, inactive SLE, patients with other autoimmune disease, and healthy individuals. Six proteins showed increased abundance in active SLE (A) and inactive SLE (I) compared to the C and O groups, but not between groups A and I. There were two transthyretin (TTR) fragments or proteins with a structure similar to TTR (accession numbers: PDB: 1GKO_A and 2PAB_A), retinol-binding protein 4 (RBP4) isoform X1 (no information in databases such as UNIPROT), and antibody fragments. Two proteins, APO-AIV and SP-40,40, were upregulated in group A than in O and C and in group I versus C, but not in group I versus O. Therefore, we suggest these proteins to be considered as candidates for the diagnosis of SLE.

Immune Profiling and Precision Medicine in Systemic Lupus Erythematosus

“…More than 241 SLE candidate proteomic biomarkers have been discovered with mass spectrometry analysis and 28 candidate biomarkers were validated in independent cohorts or studies. Ferreira et al identified candidate lupus diagnosis and activity markers with two-dimensional differential gel electrophoresis and mass spectrometry [112]. Limited numbers of lupus participants, typically 5 to 20, and variable experimental conditions in each study warrant validation of these candidate protein biomarkers.…”

Expression profile and diagnostic value of circRNAs in peripheral blood from patients with systemic lupus erythematosus

“…Due to the heterogeneous clinical manifestations and unpredictable disease course, accurate diagnosis is important for correct treatment and good prognosis of patients with SLE; however, the accurate diagnosis of SLE is difficult due to this heterogeneity of clinical manifestations and the ambiguity of the pathogenesis (3)(4)(5)(6). Currently, there is a lack of sensitive and specific diagnostic methods for SLE, but there have been an increased number of studies investigating novel biomarkers for improved SLE diagnosis (7)(8)(9).…”