Nurses' Perceptions of Wear-off Effects Following Immunoglobulin Replacement Therapy

Abstract

S U N D A Y 247 Late Onset Invasive Pneumococcal Disease in a Patient with IRAK4 Deficiency Michael David O’Sullivan, Catherine Stroud, Mario Abinun, Rainer Doffinger, Steven O’Reilly, Marzena Ciechomska, Dawn Barge, Rebecca Treacy, Stephen Owens, Terry Flood, Andrew Gennery, Sophie Hambleton; Immunology Department, PathWest Laboratory Medicine, Perth, Australia, Department of Immunology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom, Paediatric Immunology & Infectious Diseases Department, Great North Children’s Hospital, Newcastle upon Tyne, United Kingdom, Department of Clinical Biochemistry and Immunology, Addenbrooke’s Hospital, Cambridge, United Kingdom, East Anglian Medical Genetics Service, Addenbrooke’s Hospital, Cambridge, United Kingdom. RATIONALE: Primary immunodeficiencies due to defects in Toll-like receptor (TLR) signalling through MyD88 and IRAK4 are associated with susceptibility to invasive pneumococcal disease (IPD) with onset of infections at a young age and resolution by early teenage years. We describe a patient diagnosed with IRAK4 deficiency following her second episode of life-threatening IPD at 16 years old, despite antibiotic prophylaxis since the first episode at 13 years. METHODS: Serial measurement of serotype-specific pneumococcal antibodies was performed by ELISA. In vitro evaluation of TLR function was performed by assessing shedding of CD62L from granulocytes and cytokine production by peripheral blood mononuclear cells (PMBCs) in response to TLR agonists. Exons 2-12 of IRAK4 were sequenced and protein expression was assessed by Western blot. RESULTS: Antibody responses to pneumococcal polysaccharide vaccination were poorly sustained for most serotypes and there was no response to one infecting serotype. CD62L shedding and PBMC cytokine production in response to TLR agonists were markedly abnormal. A heterozygous mutation in exon 8 of IRAK4 (c. 877C>T) was detected, and a diseaseassociated polymorphism (c. 1282G>A) was detected in exon 11. Expression of IRAK4 protein was absent by Western blot. CONCLUSIONS: While the clinical and immunologic features of this patient are consistent with those previously described in association with MyD88 and IRAK4deficiency, this case is novel in the relatively late age of onset of IPD. It is possible that this patient had a second IRAK4 mutation outside exons 2-12 or null allele that resulted in the absence of IRAK4 protein expression.