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Published in Blood - 14 Feb 2022

Goncalves P, Doisne JM, Eri T, Charbit B, Bondet V, Posseme C, Llibre A, Milieu Intérieur Consortium , Casrouge A, Lenoir C, Neven B, Duffy D, Fischer A, Di Santo JP, ,

Link to Pubmed [PMID] – 35157765

Link to DOI – blood.202101465410.1182/blood.2021014654

Blood 2022 02; ():

Both innate and adaptive lymphocytes have critical roles in mucosal defense that contain commensal microbial communities and protect against pathogen invasion. Here we characterize mucosal immunity in human severe combined immunodeficiency (SCID) patients receiving hematopoietic stem cell transplantation (HSCT) with or without myeloablation. We confirmed that pre-transplant conditioning impacted on innate (NK, ILC) and adaptive (B and T cells) lymphocyte reconstitution in these SCID patients and now demonstrate that this further extends to generation of Th2 and Tc2 cells. Using an integrated approach to assess nasopharyngeal immunity, we identify a local mucosal defect in type 2 cytokines, mucus production and a selective local IgA deficiency in HSCT-treated SCID patients with genetic defects in IL2RG/GC or JAK3. These patients have a reduction in IgA-coated nasopharyngeal bacteria and exhibit microbial dysbiosis with increased pathobiont carriage. Interestingly, IVIG replacement therapy can partially normalize nasopharyngeal Ig profiles and restore microbial communities in GC/JAK3 patients. Together, our results suggest a potential non-redundant role for type 2 immunity and/or of local IgA antibody production in the maintenance of nasopharyngeal microbial homeostasis and mucosal barrier function.

https://pubmed.ncbi.nlm.nih.gov/35157765