X-linked Inhibitor of Apoptosis Complicated by Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) and Granulomatous Hepatitis

Cathal L Steele; Matthew Doré; Sandra Ammann; Maurice Loughrey; Angeles Montero; Siobhan O Burns; Emma C Morris; Bobby Gaspar; Kimberly Gilmour; Shahnaz Bibi; Hiba Shendi; Lisa Devlin; Carsten Speckmann; David M Edgar

doi:10.1007/s10875-016-0320-3

X-linked Inhibitor of Apoptosis Complicated by Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) and Granulomatous Hepatitis

J Clin Immunol. 2016 Oct;36(7):733-8. doi: 10.1007/s10875-016-0320-3. Epub 2016 Aug 5.

Authors

Affiliations

¹ Regional Immunology Service, Royal Victoria Hospital, The Belfast Trust, Belfast, UK. [email protected].
² Regional Immunology Service, Royal Victoria Hospital, The Belfast Trust, Belfast, UK.
³ Centre for Chronic Immunodeficiency, University Medical Centre Freiburg, Freiburg, Germany.
⁴ Royal Victoria Hospital, The Belfast Trust, UK and Queen's University Belfast, Belfast, UK.
⁵ Royal Brompton and Harefield Hospitals NHS Foundation Trust, London, UK.
⁶ Department of Immunology, Royal Free London NHS Foundation Trust, University College London Institute of Immunity and Transplantation, London, UK.
⁷ University College London Institute of Child Health, London, UK.
⁸ Department of Immunology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
⁹ Department of Paediatrics and Adolescent Medicine, Germany and Centre for Chronic Immunodeficiency, University Medical Centre Freiburg, Freiburg, Germany.
¹⁰ Regional Immunology Service, Royal Victoria Hospital, The Belfast Trust, Queen's University Belfast, Belfast, UK.

PMID: 27492372
DOI: 10.1007/s10875-016-0320-3

Abstract

The X-linked inhibitor of apoptosis (XIAP) deficiency is a primary immunodeficiency characterized by Epstein-Barr virus (EBV)-driven hemophagocytic lymphohistiocytosis (HLH), splenomegaly, and colitis. Here, we present, for the first time, granulomatous hepatitis and granulomatous and lymphocytic interstitial lung disease (GLILD) as manifestations of XIAP deficiency. We report successful treatment of GLILD in XIAP deficiency with rituximab and azathioprine and discuss the role of XIAP deficiency in immune dysregulation.

Keywords: Azathioprine; GLILD; Granulomatous hepatitis; Rituximab; XIAP deficiency.

Publication types

Case Reports

MeSH terms

Azathioprine / therapeutic use
Biomarkers
Biopsy
Bone Marrow / pathology
Child, Preschool
Female
Genetic Diseases, X-Linked / complications*
Genetic Diseases, X-Linked / diagnosis
Genetic Diseases, X-Linked / genetics
Genetic Diseases, X-Linked / therapy
Hepatitis / complications*
Hepatitis / diagnosis
Hepatitis / therapy
Humans
Immunoglobulins, Intravenous / therapeutic use
Immunologic Factors / therapeutic use
Immunophenotyping
Liver / pathology
Lung Diseases, Interstitial / complications*
Lung Diseases, Interstitial / diagnosis
Lung Diseases, Interstitial / drug therapy
Lymph Nodes / pathology
Lymphocytes / immunology
Lymphocytes / metabolism
Lymphohistiocytosis, Hemophagocytic / complications*
Lymphohistiocytosis, Hemophagocytic / diagnosis
Lymphohistiocytosis, Hemophagocytic / therapy
Lymphoproliferative Disorders / complications*
Lymphoproliferative Disorders / diagnosis
Lymphoproliferative Disorders / genetics
Lymphoproliferative Disorders / therapy
Male
Mutation
Pedigree
Phenotype
Respiratory Function Tests
Rituximab / therapeutic use
Tomography, X-Ray Computed
X-Linked Inhibitor of Apoptosis Protein / genetics

Substances

Biomarkers
Immunoglobulins, Intravenous
Immunologic Factors
X-Linked Inhibitor of Apoptosis Protein
XIAP protein, human
Rituximab
Azathioprine

Supplementary concepts

Lymphoproliferative Syndrome, X-Linked, 2