The role of proteomics in defining autoimmunity

ABSTRACT

Introduction

Proteomics, i.e. the study of the set of proteins produced in a cell, tissue, organism, or biological entity, has made possible analyses and contextual comparisons of proteomes/proteins and biological functions among the most disparate entities, from viruses to the human being. In this way, proteomic scrutiny of tumor-associated proteins, autoantigens, and pathogen antigens offers the tools for fighting cancer, autoimmunity, and infections.

Areas covered

Comparative proteomics and immunoproteomics, the new scientific disciplines generated by proteomics, are the main themes of the present review that describes how comparative analyses of pathogen and human proteomes led to re-modulate the molecular mimicry concept of the pre-proteomic era. I.e. before proteomics, molecular mimicry – the sharing of peptide sequences between two biological entities – was considered as intrinsically endowed with immunologic properties and was related to cross-reactivity. Proteomics allowed to redefine such an assumption using physicochemical parameters according to which frequency and hydrophobicity preferentially confer an immunologic potential to shared peptide sequences.

Expert opinion

Proteomics is outlining peptide platforms to be used for the diagnostics and management of human diseases. A Molecular Medicine targeted to obtain healing without paying the price for adverse events is on the horizon. The next step is to take up the challenge and operate the paradigm shift that the current proteomic era requires.

KEYWORDS:

• Autoimmunity: comparative proteomics
• immunoproteomics
• molecular mimicry
• peptide epitopes
• peptide-based therapies

Article highlights

• Since 2000, proteomics has rapidly grown and provided a comprehensive description of living cells in terms of their structural and functional components. Sequences, structures, interactions, physiological functions, and pathological alterations of the human proteins have been detailed and are today described in public databases, such as NCBI and UniProt.

• In parallel, proteomics has made available microbial proteomes, thus allowing comprehensive proteome comparisons as well as analyses of the pathogen vs. human relationships at the peptide level, with a focus on infectious diseases and their impact on the human immune system.

• Then, as a logical step forward, integration of immunology into proteomics, i.e. immunoproteomics, has led to the definition of a peptide epitope in terms of immunogenicity and autoimmunity.

• Indeed, immunoproteomics has defined the role of molecular mimicry in generating autoimmunity by showing that the immunological information contained in a minimal immune determinant, i.e. a penta-/hexapeptide, is inversely related to the peptide frequency in the host proteome

• Definition of autoimmunity and of immune peptide determinants is opening the way to Molecular Medicine, a medical model where protein targets are mathematically defined at the peptide level. Such an approach might be the tool for defending human health without incurring collateral harmful effects.

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Supplementary material

Supplemental data for this article can be accessed here.