Cytomegalovirus infection in infants with autoimmune lymphoproliferative syndrome (ALPS)

Abstract

SUMMARYFas-mediated apoptosis may be one of the effector pathways leading to the elimination of virus-infected cells. Cytomegalovirus (CMV) infection in two brothers with Fas deficiency associated with autoimmunity and benign lymphoproliferation (ALPS) provided a unique opportunity to study the clinical course of CMV infection in children with defective apoptosis. The clinical courses of two brothers with autosomal dominant ALPS who were infected with CMV in the neonatal period are described. CMV was detected from throat and urine culture from the brothers. ALPS was confirmed by in vitro anti-CD95 MoAb-induced T lymphocyte apoptosis assay and subsequent sequencing and identification of mutations in the Fas gene. A de novo mutation in the Fas gene, leading to a truncated cytoplasmic Fas product, was associated with autosomal dominant ALPS in a mother and her two sons. Both boys had evidence of CMV infection acquired early in infancy which cleared by the age of 2±3 years. There were no neurodevelopmental sequelae. The natural history of CMV infection in two infants with ALPS was similar to that described in normal children.

Immunity to Microbes: Lessons from Primary Immunodeficiencies

“…Although viral infections (CMV, respiratory syncytial virus, other respiratory viruses, and enteroviruses) have been associated with the onset of the disease, the same has been described for Klebsiellae species and Plasmodium falciparum (41). Increased susceptibility to viral infections has not been described with other defects in cytolytic activity; patients with ALPS (autoimmune lymphoproliferative syndrome), a less-severe perturbation of lymphocyte homeostasis associated with Fas, FasL, and caspase-10 defects, show no increased susceptibility to any infection (4,81). In contrast, two ALPS patients carrying caspase-8 mutations had severe mucocutaneous herpes simplex virus infections (17).…”

Essential Roles of Perforin in Antigen-Specific Cytotoxicity Mediated by Human CD4+ T Lymphocytes: Analysis Using the Combination of Hereditary Perforin-Deficient Effector Cells and Fas-Deficient Target Cells

“…Patients with ALPS usually present with enlargement of lymphoid organs resulting from accumulation of CD3 ϩ TCR␣␤ ϩ CD4 Ϫ CD8 Ϫ T lymphocytes and with autoimmune disorders; however, severe viral infections are rare in these patients (45,46). In contrast, FHL is a fatal disorder characterized by fever, skin rashes, hepatosplenomegaly, pancytopenia, hypertriglyceridemia, coagulopathy, and neurological involvement.…”

Autoimmunity in human primary immunodeficiency diseases

“…62,64 The precise trigger for the clinical features of the disease is still unknown, but common childhood herpes virus infections (human herpesvirus 6, cytomegalovirus, and EBV infections) that induce a lymphoproliferative response though cleared normally may be involved. 65 The prognosis for children with Fas deficiency is generally good unless they have the very rare homozygous form of the disease, for which early BMT is recommended. The heterozygous form tends to improve spontaneously with age and without treatment.…”