David Pozo Pérez
Professor of Biochemistry and Molecular Biology at the University of Seville, principal investigator at CABIMER (CSIC-US) in the Laboratory of Cellular and Molecular Neuroimmunology
The study, led by scientists at the La Jolla Institute for Immunology in California (United States), is relevant to scientists who have been supporting the important role of the immune system in the natural history of ALS, both in its onset and severity. The work, published in the journal Nature, has several fundamental aspects that support its methodological soundness and main conclusions:
- It formally demonstrates, for the first time in humans, an autoimmune response mediated by CD4+ T lymphocytes, which recognise as a source of antigenicity certain epitopes derived from various peptide sequences corresponding to the C9orf72 protein, whose gene is mutated in around 40% of cases of familial ALS.
- These specific responses are associated with the secretion of IL-4 and IL-10 cytokines and do not appear to depend on age or time elapsed since diagnosis, suggesting that they persist once the disease has developed.
- The study cannot rule out the possibility that other patients with familial or sporadic ALS may present other types of responses with different autoimmune/inflammatory components.
- The autoreactive responses have both inflammatory and anti-inflammatory/immunomodulatory components, and the study is able to associate those patients with a predicted longer survival time (according to the ENCALS model) with profiles with higher secretion of the anti-inflammatory cytokine IL10 secreted by CD4+ T cells autoreactive to C9orf72 in various epitopes.
It should be noted that a pathology with autoimmune components does not necessarily imply that it is an autoimmune pathology per se, with all that this implies, such as type I diabetes, multiple sclerosis or lupus, for example.
Much remains to be learned, from the source of presentation of these autoantigens to the role of these altered immune system responses in the central nervous system, including the mechanisms of action involved, but these studies definitely focus on interventions based on intelligent manipulation of the immune system in ALS, something long suspected by many.