The present invention relates generally to the diagnosis, treatment, and monitoring of Chronic Inflammatory Response Syndrome (CIRS), kits for use in the methods, and pharmaceutical compositions for use in the methods of treatment. The invention specifically relates to the diagnosis, treatment and monitoring of CIRS through a comprehensive approach comprising an assessment of a subject for case definition parameters and a proteogenomic analysis. The proteogenomic analysis for the diagnosis, treatment, and monitoring of CIRS is based on identifying proteins and/or genes that are differentially expressed in subjects suffering from CIRS compared to healthy subjects.