The spectrum of autoantibodies in IPEX syndrome is broad and includes anti-mitochondrial autoantibodies.
IPEX syndrome is a congenital disorder of immune regulation caused by mutations in the FOXP3 gene, which is required for the suppressive function of naturally arising CD4 + CD25 + regulatory T cells. In this case series we evaluated serum samples from 12 patients with IPEX syndrome for the presence of common autoantibodies associated with a broad range of autoimmune disorders. We note that 75% of patients (9/12) had 1 or more autoantibodies, an incidence far above the cumulative rate observed in the general population. The range of autoantibodies differed between patients and there was no predominant autoantibody or pattern of autoantibodies present in this cohort. Surprisingly, one patient had high-titer anti-mitochondrial antibodies (AMA) typically associated with primary biliary cirrhosis (PBC) although the patient had no signs of cholestasis. PBC is a well-characterized autoimmune disease that occurs primarily in women and includes the serological hallmarks of serum AMA and elevated IgM which were both present in this patient. PBC is virtually absent in children with the exception of one reported child with interleukin 2 receptor α (CD25) deficiency which is associated with an IPEX-like regulatory T cell dysfunction. Based on the present data and the available literature we suggest a direct role for CD4 + CD25 + regulatory T cells in restraining B cell autoantibody production and that defects in regulatory T cells may be crucial to the development of PBC.
Tsuda
Masanobu
M
Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA 95616, USA.
Torgerson
Troy R
TR
Selmi
Carlo
C
Gambineri
Eleonora
E
Carneiro-Sampaio
Magda
M
Mannurita
Sara Ciullini
SC
Leung
Patrick S C
PS
Norman
Gary L
GL
Gershwin
M Eric
ME
D000293:Adolescent; D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D015704:CD4 Antigens / Q000096:biosynthesis; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics; D004252:DNA Mutational Analysis; D004485:Eczema; D000939:Epitopes; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000151:congenital / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology; D007223:Infant; D007231:Infant, Newborn; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008105:Liver Cirrhosis, Biliary; D008297:Male; D009154:Mutation / Q000235:genetics; D016884:Polyendocrinopathies, Autoimmune; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D001323:Autoantibodies; D015704:CD4 Antigens; D000939:Epitopes; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit