title: Primary immunodeficiencies (PIDs) presenting with cytopenias.
abstract: Autoimmune manifestations are increasingly being recognized as a component of several forms of primary immunodeficiencies (PID). Defects in purging of self-reactive T and B cells, impaired Fas-mediated apoptosis, abnormalities in development and/or function of regulatory T cells, and persistence of immune activation as a result of inability to clear infections have been shown to account for this association. Among autoimmune manifestations in patients with PID, cytopenias are particularly common. Up to 80% of patients with autoimmune lymphoproliferative syndrome (ALPS) have autoantibodies, and autoimmune hemolytic anemia and immune thrombocytopenia have been reported in 23% and 51% of ALPS patients, and may even mark the onset of the disease. ALPS-associated cytopenias are often refractory to conventional treatment and represent a therapeutic challenge. Autoimmune manifestations occur in 22% to 48% of patients with common variable immunodeficiencies (CVIDs), and are more frequent among CVID patients with splenomegaly and granulomatous disease. Finally, autoimmune cytopenias have been reported also in patients with combined immunodeficiency. In particular, autoimmune hemolytic anemia is very common among infants with nucleoside phosphorylase deficiency. While immune suppression may be beneficial in these cases, full resolution of the autoimmune manifestations ultimately depends on immune reconstitution, which is typically provided by hematopoietic cell transplantation.
authors.affiliation: Manton Center for Orphan Disease Research and Division of Immunology, Children's Hospital Boston, Boston, MA 02115, USA. luigi.notarangelo@childrens.harvard.edu
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency; D000744:Anemia, Hemolytic, Autoimmune / Q000209:etiology*; D056735:Autoimmune Lymphoproliferative Syndrome / Q000209:etiology*; D002675:Child, Preschool; D017074:Common Variable Immunodeficiency / Q000097:blood / Q000150:complications / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000097:blood* / Q000150:complications / Q000235:genetics / Q000601:surgery; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D016131:Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D011683:Purine-Nucleoside Phosphorylase / Q000172:deficiency; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000209:etiology; D017634:Self Tolerance / Q000276:immunology; D016511:Severe Combined Immunodeficiency / Q000097:blood / Q000150:complications / Q000235:genetics; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D011683:Purine-Nucleoside Phosphorylase; D000243:Adenosine Deaminase