Hemophagocytic lymphohistiocytosis and primary immune deficiency disorders

Hemophagocytic lymphohistiocytosis (HLH) is characterized by uncontrolled immune activation and is traditionally associated with inherited gene defects or acquired causes. In addition to abnormalities in cytotoxic granules and lysosomes, various primary immune deficiency disorders (PID) have been identified among patients suffering from HLH. Our purpose was twofold: to better characterize and detail the association between PID and HLH.     

Monogenic polyautoimmunity in primary immunodeficiency diseases

Primary immunodeficiency diseases (PIDs) consist of a large group of genetic disorders that affect distinct components of the immune system. PID patients are susceptible to infection and non-infectious complications, particularly autoimmunity. A specific group of monogenic PIDs are due to mutations in genes that are critical for the regulation of immunological tolerance and immune responses. This group of monogenic PIDs is at high risk of developing polyautoimmunity (i.e., the presence of more than one autoimmune disease in a single patient) because of their impaired immunity. In this review, we discuss the mechanisms of autoimmunity in PIDs and the characteristics of polyautoimmunity in the following PIDs: IPEX; monogenic IPEX-like syndrome; LRBA deficiency; CTLA4 deficiency; APECED; ALPS; and PKCδ deficiency.