Sequential Asymptomatic Enterovirus Infections in a Patient with Major Histocompatibility Complex Class II Primary Immunodeficiency

Abstract

Patients with primary immunodeficiencies are usually susceptible to enterovirus infections and have higher risks to develop severe clinical forms. We report a unique description of a boy with major histocompatibility complex class II (MHC-II) deficiency infected by 9 different enterovirus serotypes during a 2-year period, with very mild clinical symptoms, probably due to the immunoglobulin therapy he was receiving. CASE REPORTT he case patient is the older child of Tunisian consanguineous healthy parents. He was born in 2002 with, apparently, no neonatal pathology. Breastfed for 20 months, he had a history of multiple episodes of upper respiratory infections and diarrhea with failure to thrive (Ϫ2 standard deviations in weight and size). At the age of 3 months, he developed a chronic diarrhea (6 to 7 stools per day) which required hospitalization. He was hospitalized again at 4 years of age for diarrhea and dehydration; the diagnoses of mucovicidosis and of celiac disease were ruled out based on negative sweat testing and the results of duodenal fibroscopy and biopsy, respectively. At 5 years of age, because of multiple respiratory infections, a computed tomography thoracic scan was performed and found a diffuse bronchiectasis. His vaccination history against poliomyelitis included four doses of trivalent oral poliovirus vaccine (OPV) administered at 3, 4, 5, and 18 months of age; he received another dose of OPV at 4 years of age during a subnational polio mass vaccination campaign. In December 2007, major histocompatibility (MHC) class II deficiency was diagnosed based on the defect of expression of MHC class II molecules on the surface of resting peripheral blood mononuclear cells, with confirmation by expression study on phytohemagglutinin-activated blast cells, as assessed by flow cytometry. A severe CD4 lymphopenia (6%) was found, along with abnormal immunoglobulin titers of 644 mg/dl for IgG (normal, 929 Ϯ 228 mg/dl), 74 mg/dl for IgA (normal, 56 Ϯ 18 mg/dl), and 132 mg/dl for IgM (normal, 93 Ϯ 27 mg/dl) (1). Subsequently, he was treated on a monthly basis with substitutive intravenous immunoglobulins and was regularly followed by the expert physicians and nurses of the Bone Marrow Transplantation Center in Tunisia, specialized in managing and providing care for these patients. Bone marrow transplantation could not be performed due to the unavailability of a compatible donor. The molecular analysis did not show the presence of the recurrent 752delG26/RFXANK gene mutation that is observed in most MHC class II-deficient Maghrebian patients (2). At each visit and prior to immunoglobulin transfusion, a blood sample was collected for residual immunoglobulin titration. A complete medical examination was performed; all clinical symptoms present at the day of the visit and those that occurred during the previous month were recorded and appropriate treatment prescriptions were provided.In , approximately 15 months of followup) were previously published in a paper summarizing the study results for the whole cohort (...

Poliovirus excretion following vaccination with live poliovirus vaccine in patients with primary immunodeficiency disorders: clinicians’ perspectives in the endgame plan for polio eradication

“…As reported by Driss et al [ 19 ] a Tunisian patient diagnosed with MHC II deficiency exhibited sequential infection by 9 different enterovirus serotypes within a 2-year period. El-Sayed et al [ 15 ] also reported on a PID patient who demonstrated evolution of VDPV in his stool samples over time which again highlights the importance of follow up as they may demonstrate intermittent shedding or evolution with time.…”

Modeling the prevalence of immunodeficiency-associated long-term vaccine-derived poliovirus excretors and the potential benefits of antiviral drugs

“…Figure 1 suggests that once individuals recover from infection, they can potentially become re-infected. No known cases of longterm re-infection after recovery from a long-term infection exist, but some evidence exists of many repeated poliovirus and other enterovirus infections in a PID patient, with one poliovirus infection of at least 4 months [ 54 ].

Fig.

…”

Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies

“…Patients with a variety of PIDDs are unusually susceptible to EV [ 238 ]. The most susceptible groups are patients with primary antibody deficiency such as XLA, CVID, and hyper-IgM syndrome (HIGMS) as well as those having SCID and major histocompatibility class II deficiency [ 239 , 240 ]. The most severe form of infection has been described in patients with XLA due to the profound deficiency of immunoglobulins essential for viral neutralization during infection.…”