Post-translational modified proteins are biomarkers of autoimmune-processes: NETosis and the inflammatory-autoimmunity connection.
Basic research is showing new mechanisms involved in early immune responses and Neutrophil Extracellular Trap (NET) formation (or NETosis) is of key importance as first line defense against bacteria, virus and protozoa. Enzymatic modification of arginine in citrulline in histones is the prerequisite of NETosis being it necessary for decondensation and extrusion of DNA from cells; it is conceivable that other post translational modifications may occur during this event. There is consensus in considering that post translational modified proteins may elicit an autoimmune response that leads to the formation of autoantibodies. Several autoimmune diseases seem to share these pathogenic mechanisms, in particular Rheumatoid arthritis, Systemic Lupus Erythematosus, Small Vessel Vasculitis and Anti-Phospholipid Syndrome, which are all characterized by high levels of circulating autoantibodies. Autoimmunity has, however, different targets and elicits different clinical responses. It seems reasonable to hypothesize that although NETosis is common to all the conditions above, NET components are different and potentially responsible for different autoimmune responses. On the other hand also showing whether circulating NET remnants are present as free structures in blood/biological fluids and determine their levels is relevant to autoimmunity. This review is intended to discuss the rationale for utilizing new discoveries that could be of rapid clinical application and lead to the development of early biomarkers of autoimmunity to predict and treat otherwise serious conditions.
Laboratory on Pathophysiology of Uremia, Scientific Institute for Research and Health Care (IRCCS), Istituto Giannina Gaslini, Genoa, Italy.
Maurizio
M
Bruschi
Laboratory of Mass Spectrometry-Core Facility, Scientific Institute for Research and Health Care (IRCCS), Istituto Giannina Gaslini, Genoa, Italy.
Andrea
A
Petretto
Laboratory on Pathophysiology of Uremia, Scientific Institute for Research and Health Care (IRCCS), Istituto Giannina Gaslini, Genoa, Italy.
Roberta
R
Bertelli
Department of Clinical and Experimental Medicine, Research Center University of Parma, Parma, Italy.
Maricla
M
Galetti
Division of Nephrology, Dialysis, and Transplantation, Scientific Institute for Research and Health Care (IRCCS), Istituto Giannina Gaslini, Genoa, Italy.
Alice
A
Bonanni
Clinical Immunology and Allergy Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy.
Federico
F
Pratesi
Clinical Immunology and Allergy Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy.
Paola
P
Migliorini
Laboratory on Pathophysiology of Uremia, Scientific Institute for Research and Health Care (IRCCS), Istituto Giannina Gaslini, Genoa, Italy.
Giovanni
G
Candiano
Department of Clinical and Experimental Medicine, Research Center University of Parma, Parma, Italy.
Augusto
A
Vaglio
Division of Nephrology, Dialysis, and Transplantation, Scientific Institute for Research and Health Care (IRCCS), Istituto Giannina Gaslini, Genoa, Italy; Laboratory on Pathophysiology of Uremia, Scientific Institute for Research and Health Care (IRCCS), Istituto Giannina Gaslini, Genoa, Italy. Electronic address: gmarcoghiggeri@gaslini.org.
Gian Marco
GM
Ghiggeri
D015551:Autoimmunity; D015415:Biomarkers / Q000378:metabolism; D065206:Extracellular Traps / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism*
D015415:Biomarkers; D011506:Proteins
Autoantibodies; Autoimmunity; Carbamylation; Citrullinated proteins; Neutrophil extracellular traps