Flow cytometry biomarkers distinguish DOCK8 deficiency from severe atopic dermatitis.
DOCK8 deficiency is a primary immunodeficiency characterized by recurrent sinopulmonary infections, dermatitis with cutaneous infections, elevated serum IgE levels, eosinophilia, and a high incidence of food allergy. Given the seriousness of DOCK8 deficiency, it is important to recognize it early and initiate appropriate therapy. Diagnosis relies on examining DOCK8 protein expression and sequencing of the 48 exons in the DOCK8 gene, but these assays are not always readily available. A major problem facing clinicians is that DOCK8 deficiency shares many clinical and laboratory features with severe atopic dermatitis. Here, we have identified biomarkers routinely measured by flow cytometry on whole blood in clinical immunology laboratories that may be used in distinguishing DOCK8 deficiency from severe atopic dermatitis. The use of these biomarkers may help the clinician identify those patients who are most likely to have DOCK8 mutations and would benefit from further specialized diagnostic testing.
Division of Immunology, Boston Children's Hospital, Boston, MA, USA.
Erin
E
Janssen
Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA.
Erdyni
E
Tsitsikov
Department of Pediatrics, Kuwait University, Kuwait City, Kuwait.
Waleed
W
Al-Herz
University Montpellier 2 and CNRS Institute of Human Genetics, Montpellier, France.
Gerard
G
Lefranc
Unit of Medical Genetics, Saint Joseph University, Beirut, Lebanon.
Andre
A
Megarbane
Department of Pediatrics, University of Kansas Medical Center, Kansas City, KS, USA; Department of Internal Medicine, Division of Genetics, Endocrinology & Metabolism, University of Kansas Medical Center, Kansas City, KS, USA.
Majed
M
Dasouki
Division of Immunology, Boston Children's Hospital, Boston, MA, USA.
Francisco A
FA
Bonilla
Division of Immunology, Boston Children's Hospital, Boston, MA, USA.
Talal
T
Chatila
Division of Immunology, Boston Children's Hospital, Boston, MA, USA.
Lynda
L
Schneider
Division of Immunology, Boston Children's Hospital, Boston, MA, USA. Electronic address: raif.geha@childrens.harvard.edu.
Raif S
RS
Geha
D015415:Biomarkers; D003876:Dermatitis, Atopic / Q000175:diagnosis* / Q000378:metabolism; D003937:Diagnosis, Differential; D005091:Exons; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D016130:Immunophenotyping; D016131:Lymphocyte Subsets / Q000378:metabolism; D009154:Mutation; D016017:Odds Ratio; D010641:Phenotype
D015415:Biomarkers; C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors
Atopic dermatitis;; B cell; DOCK8;; Hyper-IgE;; T cell;