Allergic Phenotype And Genotype Characteristics Of Primary Immunodeficiency Diseases

OBJECTIVE: In this study,we retrospectively analyzed the clinical data of primary immunodeficiency disease patients in our center,collected their allergic phenotypes and genotypes,and conducted a literature review to summarize the clinical manifestations and common genotypes of primary immunodeficiency disease patients with allergic phenotypes,in order to improve clinicians’ understanding of the allergic phenotypes of primary immunodeficiency disease and provide more clues for the diagnosis and treatment of primary atopic diseases.METHODS: Demographic information,clinical data and laboratory test results of patients with primary immunodeficiency diseases hospitalized in Shenzhen Children’s Hospital from October 2014 to October 2022 were retrospectively collected,and their allergy-related phenotypic and genotypic characteristics were statistically analyzed.Relevant keywords were searched through Pubmed,MEDline,and GOOLE scholar to collect internationally reported monogenic diseases with allergic phenotypes,excluding duplicate cases,cases with the same genotype and allergic phenotype,and genotypes not included in the 2022 edition of IUIS-IEI.RESULTS: A total of 107 patients with primary immunodeficiency disease were included in our center,with a total of 43 genetic mutations,including 9 of the 10 major categories,61 combined allergy-related phenotypes,and 33 mutated genes involved.The most common allergic symptoms were eczema / atopic dermatitis(28),followed by food allergy(27),and allergic rhinitis(4).Eosinophilia was the most common indicator of allergy-related laboratory abnormalities(27),followed by elevated total serum Ig E(19).Among the 61 patients with primary immunodeficiency disease with combined allergy-related phenotypes,combined immunodeficiencies with syndromic features was the most common,with 14(23.0%),followed by combined immunodeficiency disease with 11(18.0%),and among the 43 mutated genes,SATA3 mutations were the most frequent(7),followed by CD40 LG and PIK3 CD mutations(4 cases,respectively).Allergy-associated phenotypes were seen in 93.3% of patients with combined immunodeficiencies with syndromic features,83.3% of patients with diseases of immune dysregulation,75.0% of patients with defects in intrinsic and innate immunity,and no allergic phenotypes in patients with complement deficiencies.Eosinophilia was most common in combined immunodeficiency diseases(7),75.0% of patients with diseases of immune dysregulation had eosinophilia.Elevated serum total Ig E was seen most frequently in combined immunodeficiencies with syndromic features(8),followed by auto-inflammatory diseases(5).Elevated total serum Ig E was seen in 85.7% of patients with STAT3 gene mutations..A total of 36 papers involving 42 mutated genes were searched in the database by relevant keywords,with combined immunodeficiency with syndromic features being the most frequent,followed by combined immunodeficiency and diseases of immune dysregulation.Complement deficiency and bone marrow failure did not retrieve genetic mutations combining allergic phenotypes.Primary immunodeficiency disorders account for a large proportion of monogenic allergic diseases.Primary immunodeficiency diseases accounted for the largest proportion of monogenic allergic diseases(84.0%).CONCLUSION: Primary immunodeficiency disorders with combined allergy-related phenotypes are not uncommon.Allergic phenotypes in patients with PID are easily overlooked,and assessment of allergic phenotypes is an important part of the evaluation of PID patients’ conditions.