It is difficult to fulfill Koch’s postulates when considering the etiology of autoimmune diseases (AIDs), which are multifactorial diseases where a primary role is played by genetic factors associated with environmental factors responsible for their clinical expressions [359]. Direct evidence is restricted to transplacental transmission of IgG pathogenic autoantibodies (Aab) from the affected mother to her fetus, such as in neonatal myasthenia gravis, polychondritis and Graves’ disease. Indirect evidence comes mainly from AID reproduction in animal models and/or development of genetically determined AID models, and from the isolation of Aab or reactive T cells [359]. In this chapter, a multiplicity of abnormalities associated with systemic AIDs in different organs and systems will be examined.