Primary immunodeficiency as a cause of immune-mediated kidney diseases.

Primary immunodeficiency (PID) is no longer defined by infections alone, and autoimmunity is an accompanying manifestation of PID. Recurrent infections may trigger autoimmunity through molecular mimicry, bystander activation or superantigens. The diagnosis of PID is still challenging, but genetic analysis reveals the underlying link between PID and autoimmunity. Mutations in relevant genes affecting central and peripheral immune tolerance, regulatory T-cell function, expansion of autoreactive lymphocytes, antigen clearance, hyperactivation of type I interferon and nuclear factor-κB pathways have all been implicated in triggering autoimmunity in PID. Autoimmunity in PID leads to chronic inflammation, tissue damage and organ failure, and increases the mortality of patients with PID. The kidneys are inextricably linked with the immune system, and kidney diseases can be mediated by both infection and autoimmunity/inflammation in PID patients. The manifestations of kidney involvement in PID patients are very heterogeneous and include lupus nephritis, C3 glomerulopathy, kidney thrombotic microangiopathy, vasculitis and interstitial nephritis. Patients with PID-caused kidney diseases have defined immune function defects and may benefit from pathway-based biologics, stem cell transplantation or gene therapy. Early diagnosis and appropriate treatment of PID are crucial for reducing the mortality rate and improving organ function and quality of life.