Novel Combinatorial Screening for NTFs, NPCs, MMPs, and CCs in Relevance to Autoantibodies in the Serum and CSF of Veterans with GWI
Abstract
Gulf War Veterans with Gulf War Illness (GWI), a term referred to Soldiers who were deployed from 1990 to 1991 during Operations Desert Shield and Desert Storm that continue to suffer – even after 25 years – from chronic health problems. In an ongoing Department of Defense-funded study in our laboratory, evidences of increased levels of autoantibodies to neuronal proteins have been observed. This could mean that while the body is trying to protect against other foreign germs (proteins) or chemicals, it is also fighting a war within – reacting to the body’s own proteins causing untold tissue damage inflammation. How is that possible? When we analyzed clinical conditions affecting Gulf War Veterans with GWI, a wide range of complaints were reported, such as fatigue, ALS-like symptoms, fibromyalgia, headache, breathing disorders, chest pain, stomach and intestinal problems, skin ailments, social anxiety, behavioral changes, interpersonal relationship problems, and it clearly appears that the etiology is likely multi-causal. It is evident that Gulf War Veterans were able to sustain the pressures of war operations rife with stress and toxic exposures because they were strong, fit, and healthy. Nevertheless, the unique dangers posed by chemical or biological agent in a war zone is a given. Preventative measures taken were pest/insect repellents, vaccinations, intake of cholinesterase inhibitors and other supplements. These can activate the immune system both favorably and in certain situations rather unfavorably. We propose that repeated, short-term exposures to certain chemicals may lead to neurotoxicity, along with simultaneous exposure to cholinergic agents and vaccines, which can trigger multi-various cellular pathways that have potential for inciting an autoimmune response. No two individuals have the same immune response; however, they may appear to react the same. The human system is regulated by a complex network of systems such as immune, lymphatic, and neuromuscular systems that regulate the whole body. Every cell is made of proteins and enzymes that constantly activate and deactivate to generate thermodynamic force. Metabolically broken down sugar provides the needed energy. Water and fat (lipid) provides support for these interactions. These involve interactions between protein-protein, protein-DNA, protein-lipid, lipid-DNA along with other organic and inorganic compounds and air (oxygen, nitrogen, carbon-di-oxide) as an integrated approach. These processes generate lots of energy and redox potentials for the cells and neurons. During these functioning, there are lot of substrates produced to maintain the system under normal functioning. Since blood circulates through all parts of the body and cerebrospinal fluid around the brain and the spine, evaluating these body fluids for various factors/cytokines/enzymes, etc. simultaneously would provide us the needed leverage about the type of injury and the treatment strategy necessary to be employed. As mentioned above, neuronal antibodies have been observed in GWI in our ongoing study. This could happen only when the neurons have been the target of an autoimmune response due to its inability to recognize the host neuronal proteins. Hence, an urgent need is to find the extent of this defect in order to address the health symptoms of GWI. Therefore, in connection with this current proposal, we hypothesize four important biological components that could shed light on what has been going wrong and how we could possibly identify the key players. Thus, the study proposes to investigate role of the following: (1) neurotropic factors, a family of growth factors that maintain the normal functioning of the neurons; (2) neuropoietic cytokines, a group of substrates that can recruit cells to defend against any insults; (3) matrix metalloproteinase, a family of enzymes that breaks down metals to cellular matrix so that cells can maintain their structure and f
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810454
Entities
People
- Brahmajothi Mulugu
Organizations
- Duke University
- United States Army