IgG4, a subclass of IgG, has been the subject of intense scientific research, resulting in the classification of heterogeneous clinical medical conditions, defined as IgG4 Related Disease (IgG4-RD). The ongoing investigation on refining the diagnosis, classification and pathophysiology of IgG4-RD, generated further questions on the role of IgG4 in inflammation, autoimmunty and induction of diseases and syndromes. On this regard, emerging reports indicate that this subclass of immunoglobulin G, may participate on the pathophysiology of autoimmune diseases, like Rheumatoid Arthritis. These reports provide new aspects of well-defined diseases of Internal Medicine, and support the fundamental knowledge immunologists rigorously support, that IgGs' role exceeds the boundaries of infections and actively participate in regulating the host's general homeostasis.