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.

Keywords:

• Systemic lupus erythematosus
• proteomics
• 2D-DIGE
• retinol-binding protein 4 isoform X1
• SP-40,40 partial

Acknowledgements

This work was supported by Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Conselho Nacional de Desenvolvimento Científico e Tecnológico, The National Institute of Science and Technology for Vaccines [grant number CNPq-573547/2008-4], Rede Mineira de Biomoléculas [grant number CCB-RED00012-14]. HMA is a CNPq fellow (PQ). BSSL and LCFJ are CAPES and CNPq fellows, respectively, and Pro-reitoria de Pesquisa da Universidade Federal de Minas Gerais (PRPq, UFMG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Disclosure statement

All authors have reviewed the manuscript and approved submission for publication. The authors have declared no potential conflict of interest of the material included in this manuscript.

Additional information

Funding

This work was supported by Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Conselho Nacional de Desenvolvimento Científico e Tecnológico, The National Institute of Science and Technology for Vaccines [grant number CNPq-573547/2008-4], Rede Mineira de Biomoléculas [grant number CCB-RED00012-14]. HMA is a CNPq fellow (PQ). BSSL and LCFJ are CAPES and CNPq fellows, respectively, and Pro-reitoria de Pesquisa da Universidade Federal de Minas Gerais (PRPq, UFMG).