Immunodysregulation in immunodeficiency

The primary immunodeficiency diseases are often accompanied by autoimmunity, autoinflammatory, or aberrant lymphoproliferation. The paradoxical nature of this association can be explained by the multiple cells and molecules involved in immune networks that interact with each other in synergistic, redundant, antagonistic, and parallel arrangements. Because progressively more immunodeficiencies are found to have a genetic etiology, in many cases, a monogenic pathology, an understanding of why immunodeficiency is really an immune dysfunction becomes evident. Understanding the role of specific genes allows us to better understand the complete nature of the inborn error of immunity (IEI); the latter is a term generally used when a clear genetic etiology can be discerned. Autoimmune cytopenias, inflammatory bowel disease, autoimmune thyroiditis, and autoimmune liver diseases as well as lymphomas and cancers frequently accompany primary immunodeficiencies, and it is important that the practitioner be aware of this association and to expect that this is more common than not. The treatment of autoimmune or immunodysregulation in primary immunodeficiencies often involves further immunosuppression, which places the patient at even greater risk of infection. Mitigating measures to prevent such an infection should be considered as part of the treatment regimen. Treatment of immunodysregulation should be mechanism based, as much as we understand the pathways that lead to the dysfunction. Focusing on abnormalities in specific cells or molecules,