Oral Presentations - Federation of Clinical Immunology Societies

S42 Abstracts
Introduction: APECED is characterized by the early onset
of multiple organ directed autoimmunity, chronic mucocutaneous
candidiasis and ectodermal dystrophy, and caused
by recessive mutations in AIRE gene. The vast majority of
affected patients are of northern European descent,
Sardinian or Iranian Jews. We describe here a Brazilian
family affected by the disease. Material and methods: All
14 exons and flanking intronic regions of AIRE were
amplified by PCR, purified and sequenced using an
automated capillary sequencer. Results: The index patient,
LGM, is a 15-year-old boy from São Paulo. At 7 months he
developed recurrent thrush and at the age of 2 years
presented ungueal candidiasis. At 9 years his height was
119 cm (pb3), levels of IGF1 and IGFBP3 were low, and a
diagnosis of GH deficiency was made. At 12 years he
developed anti-adrenal antibodies (1/40), and at 15 years
he showed high levels of ACTH and PTH. His mother
presents oral thrush, megaloblastic anemia and hypoparathyroidism,
and his sister has recurrent candidiasis, without
signs of autoimmunity. Parents deny consanguinity.
Genomic DNA sequencing of AIRE identified a homozygous
missense mutation in exon 8 (Pro326Leu). This mutation
affects the first PHD finger domain, probably interfering
with adequate subcellular protein localization and functioning.
Conclusion: This is to our knowledge the first report
of AIRE mutations causing APECED in a Brazilian family, and
of a P326L AIRE mutation in a homozygous state. Molecular
diagnosis is important for genetic counseling and institution
of adequate therapy early in life.
doi:10.1016/j.clim.2007.03.295
F.83 NOD2 Polymorphisms in CVID: Investigation
into Associations with Gastrointestinal Pathology
and Granulomatous Disease
Kerri Packwood, Grade A Clinical Scientist in
Immunology, Clinical Immunology, Oxford Radcliffe
Hospitals NHS Trust, Oxford, OXON, England, Berne Ferry,
Principle Scientist, Clinical Immunology, Oxford Radcliffe
Hospitals NHS Trust, Oxford, OXON, England, Divya
Punwani, PhD Student, Wetherall Institute of Molecular
Medicine, Human Immunology Unit, Oxford, OXON,
England, Eduardo Lopez-Granados, Consultant
Immunologist, Clinical Immunology, Oxford Radcliffe
Hospitals NHS Trust, Oxford, OXON, England, Helen
Chapel, Consultant Immunologist, Clinical Immunology,
Oxford Radcliffe Hospitals NHS Trust, Oxford, OXON,
England
Common Variable Immunodeficiency Disorders (CVID)
are a heterogeneous group of diseases characterised by
hypogammaglobulinaemia. Associated complications
include enteropathy and granulomatous disease. These
conditions have diverse immunopathogeneses including
primary defects in B cells, T cells, macrophages, dendritic
cells, NK cells and cytokine production yet often the
underlying aetiology is unknown. Prediction of complications
would aid clinical management and we are
investigating possible disease modifier genes as a potentially
powerful tool. Classification of heterophenotypic
CVID subgroups would also enable more focused and
productive research studies. Mutations of the NOD2 gene
including gly908arg, leu1007finsc and arg702trp polymorphisms
are associated with Crohn'€s disease. We
hypothesised that NOD2 may also be a disease modifier
gene towards an enteropathic or granulomatous CVID
phenotype. Methods to examine the above three polymorphisms
were established and investigated in a cohort
of 52 CVID patients and 26 non-patient controls. Five
heterozygous NOD2 leu1007finsc mutations, two heterozygous
NOD2 gly908arg mutations and four heterozygous
NOD2 arg702trp mutations were found amongst CVID
patients giving allele frequencies of 0.048, 0.019 and
0.038 respectively. No polymorphisms were found amongst
non-patient controls. Although to date we are unable to
demonstrate a significant genotype/phenotype association,
results from this study show this as reliable
screening method for gly908arg, leu1007finsc and
arg702trp NOD2 polymorphisms. More patients are
required to conclude whether these and/or additional
NOD2 polymorphisms can define a clinical subgroup of
CVID patients likely to develop enteropathic or granulomatous
complications.
doi:10.1016/j.clim.2007.03.296
F.84 Development of Regulatory T Cells After
Thymus Transplantation in Subjects with Complete
DiGeorge Syndrome
Ivan Chinn, Fellow-In-Training, Duke University Medical
Center, Pediatrics, Durham, NC, Blythe Devlin, Assistant
Research Professor, Duke University Medical Center,
Pediatrics, Durham, NC, M. Louise Markert, Associate
Professor, Duke University Medical Center, Pediatrics,
Durham, NC
Purpose: Characterize the development of CD4+Foxp3+
regulatory Tcells in subjects with complete DiGeorge syndrome
after thymus transplantation. Background: Forty-four subjects
with complete DiGeorge syndrome, including athymia (b50
naïveTcells/cumm),havereceivedculturedpostnatalallogeneic
HLA nonmatched thymus grafts. Twenty-seven of 32
survivors are currently at 1-year or greater post-transplantation.
All 1-year survivors have naïve T cells with normal
proliferative responses to phytohemagglutinin and normal T
cell receptor repertoires. We now report the percentages of
Foxp3+ CD4+ T cells in the peripheral blood of 11 subjects who
are 1-year survivors after thymus transplantation. Five of the
subjects received peri-transplantation immunosuppression.
Five of the 11 subjects have autoimmune thyroid disease,
including one subject in the group who received immunosuppression.
Results: All eleven subjects had percentages of CD4
+Foxp3+ Tcells in the expected range compared to healthy adult
controls at various time points post-transplantation. Absolute
numbers of CD4+Foxp3+ T cells were low (12−65 cells/cumm),
reflecting the subjects’ low total T cell counts for age. Similar
percentages of regulatory T cells were found in subjects who
received immunosuppression (median 3.85%, range 3.48−5.33%)
compared with those who did not (median 4.58%, range 2.96
−7.35%). The percentages of CD4+Foxp3+ Tcells did not appear