Common Variable Immunodeficiency Associated with a De Novo IKZF1 Variant and a Low Humoral Immune Response to the SARS-CoV-2 Vaccine Díaz Alberola, Irene Jiménez Gámiz, Pilar López Nevot, Miguel Ángel CVID IKZF1 IKAROS De novo mutations R162Q Immune response SARS-CoV-2 Heterologous vaccine Humoral response T-cell response COVID-19 Acknowledgments: We thank Per Anderson for the English revision. This study is part of the doctoral thesis of Irene Díaz Alberola, within the program of Biomedicine, conducted at the University of Granada, Spain. Institutional Review Board Statement: The study was conducted in accordance with the Declaration of Helsinki, and approved by Portal de Ética de la Investigación Biomédica. Junta de Andalucía (Code: 0297-N-21). Background and Aims: Common variable immunodeficiency (CVID) comprises a group of diseases with heterogeneous clinical and immunological manifestations. Several mutations have been identified in genes encoding proteins essential for immune function. Our aim was to phenotypically and genotypically characterize a patient diagnosed with CVID and study his response to the SARSCoV- 2 vaccine. Methods: We performed a next-generation sequencing analysis, a CMIA, and an ELISA to analyze the humoral and cellular response to the SARS-CoV-2 vaccine, respectively. We also employed flow cytometry and immunoturbidimetry to assess the patient’s global immune status. Results: We found a low humoral but positive cellular response to the SARS-CoV-2 vaccine. NGS screening revealed a transition from guanine to adenine at position c.485 of the IKZF1 gene in heterozygosity, giving rise to the R162Q variant, which was not present in his parents. Conclusions: The R162Q variant of the IKZF1 gene has been associated with CVID type 13, but always with an autosomal dominant inheritance with high penetrance. Therefore, we present for the first time a case of CVID associated with a de novo heterozygous R162Q variant in the IKZF1 gene in a patient with a low humoral immune response to the complete COVID-19 vaccination program. 2022-05-10T11:16:42Z 2022-05-10T11:16:42Z 2022-04-20 journal article Díaz-Alberola, I.; Espuch-Oliver, A.; García-Aznar, J.M.; Ganoza-Gallardo, C.; Aguilera-Franco, M.; Sampedro, A.; Jiménez, P.; López-Nevot, M.Á. Common Variable Immunodeficiency Associated with a De Novo IKZF1 Variant and a Low Humoral Immune Response to the SARS-CoV-2 Vaccine. J. Clin. Med. 2022, 11, 2303. [https://doi.org/10.3390/jcm11092303] http://hdl.handle.net/10481/74786 10.3390/jcm11092303 eng http://creativecommons.org/licenses/by/3.0/es/ open access Atribución 3.0 España MDPI