TY - JOUR
T1 - Somatic mosaicism in B cells of a patient with autosomal dominant hyper IgE syndrome
AU - Alcántara-Montiel, Julio C.
AU - Staines-Boone, Tamara
AU - López-Herrera, Gabriela
AU - Berrón-Ruiz, Laura
AU - Borrego-Montoya, Carlos R.
AU - Santos-Argumedo, Leopoldo
N1 - Publisher Copyright:
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Hyper IgE syndrome (HIES) is characterized by recurrent skin abscesses, eczema, pneumonia, and high levels of serum IgE. Nonimmunologic manifestations of HIES include a characteristic face, pathologic dentition, scoliosis, bone alterations, hyperextensible joints, and vascular abnormalities. Somatic mosaicism is defined by the presence of two or more populations of cells with different genotypes in one individual. In this report, we describe one patient with classical HIES and another patient with a mild phenotype, both harboring the same genetic mutation. The patient with a mild phenotype did not present the characteristic face, had normal production of IL-17A by T CD4+ cells, but had low phosphorylation of STAT-3 in B cells. Interestingly, the mutation found in B cells was absent in other cell types analyzed, in agreement with the presence of a somatic mosaic genotype. The clinical and functional differences observed between these patients justify the use of complementary tools for a better definition of the cases. These approaches allow for a better understanding of complex phenotypes associated with somatic mosaicisms, and present the possibility to analyze the role of B lymphocytes in the pathophysiology of this disease. This knowledge has an impact on not only the treatment but also the provision of appropriate genetic counseling.
AB - Hyper IgE syndrome (HIES) is characterized by recurrent skin abscesses, eczema, pneumonia, and high levels of serum IgE. Nonimmunologic manifestations of HIES include a characteristic face, pathologic dentition, scoliosis, bone alterations, hyperextensible joints, and vascular abnormalities. Somatic mosaicism is defined by the presence of two or more populations of cells with different genotypes in one individual. In this report, we describe one patient with classical HIES and another patient with a mild phenotype, both harboring the same genetic mutation. The patient with a mild phenotype did not present the characteristic face, had normal production of IL-17A by T CD4+ cells, but had low phosphorylation of STAT-3 in B cells. Interestingly, the mutation found in B cells was absent in other cell types analyzed, in agreement with the presence of a somatic mosaic genotype. The clinical and functional differences observed between these patients justify the use of complementary tools for a better definition of the cases. These approaches allow for a better understanding of complex phenotypes associated with somatic mosaicisms, and present the possibility to analyze the role of B lymphocytes in the pathophysiology of this disease. This knowledge has an impact on not only the treatment but also the provision of appropriate genetic counseling.
KW - Hyper IgE syndrome
KW - IL-17A
KW - Somatic mosaic
KW - STAT3 phosphorylation
UR - http://www.scopus.com/inward/record.url?scp=84990854090&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84990854090&partnerID=8YFLogxK
U2 - 10.1002/eji.201546275
DO - 10.1002/eji.201546275
M3 - Article
C2 - 27488252
AN - SCOPUS:84990854090
SN - 0014-2980
VL - 46
SP - 2438
EP - 2443
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 10
ER -