There are many chronic illnesses that are referred to as autoimmune diseases such as multiple sclerosis, amyotrophic lateral sclerosis (ALS) and pemphigus vulgaris for example; the etiology of these diseases originates from the patient’s immune system attacking normal tissue.
ALS is a disease that presents as a progressive degeneration of the normal function of motor neurons resulting in paralysis and death. It has been shown that mutations in the C9ORF72 gene are commonly found in ALS and frontotemporal dementia. This gene is located on the short arm of chromosome 9 in humans. This gene contains the information for the production of the C9orf72 protein. Furthermore, in animal model studies using the mouse, it has been found that mutations in this gene result in Autoimmune-like symptoms. Transplantation of normal murine bone marrow positively impacted diseased mice with this mutation and bone marrow transplantation of diseased mice into normal animals alternatively resulted in symptoms of autoimmunity. These latter results led investigators to suspect that the C9orf72 gene is normally active in hematopoietic cells – cells residing in the bone marrow that produce circulating blood cells - in suppressing autoimmunity.
Recent findings have clearly established that mice that harbor mutations in the C9orf72 gene that result in the loss of function of the C9orf72 protein gene product develop the following symptoms –
- splenomegaly – enlarged spleen
- neutrophilia – increased population of neutrophils in the circulation
- thrombocytopenia – decreased numbers of platelets
- increased expression of inflammatory cytokines
- severe autoimmunity.
These diseased animal suffer a high mortality rate.
These data represent strong evidence that the C9ORF72 gene plays a very important role in the suppression of autoimmunity and may prove to be of future therapeutic value.