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Hyper-IgD Syndrome: Caused by Deficiency on Ras Prenylation and Trained Immunity?

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Funding

I acknowledge the financial support of Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior- CAPES; Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro- FAPERJ E-26/200.628/2022; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)- Brazil.

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Authors and Affiliations

  1. Laboratory of Immunoreceptors and Signaling, Instituto de Biofísica Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Rafael Cardoso Maciel Costa Silva

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  1. Rafael Cardoso Maciel Costa Silva
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Silva RCMC wrote the letter.

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Correspondence to Rafael Cardoso Maciel Costa Silva.

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Supplementary information

ESM 1

Supplementary Figure 1: Methodological approaches to evaluate the hypothesis: A) PBMCs-derived B lymphocytes can be collected from healthy or HIDS volunteers and cultured in specific conditions in the presence of 50ng/mL interleukin (IL)-21 and 2.5μg/mL phosphorothioate CpG-oligodeoxynucleotides (ODN) 2006. These B lymphocytes can be pre-incubated with different ERK modulators, and then polyclonally stimulated for 36 hours with 2.5μg/mL phytohemagglutinin/leucoagglutinin (PHA-L), and 15ng/mL phorbol myristate acetate (PMA). To confirm ERK modulation, Western blotting (with anti-p-ERK) of cell lysates should be performed. After 36 hours of polyclonal stimulus, the amount of IgM and IgD in culture supernatants can be measured by ELISA and the cells analyzed by ELISPOT. The ability of PBMCs-derived monocytes to eliminate infectious agents, for example gram-negative bacteria, can be assessed in vitro. B) The in vivo effects of ERK activators can be evaluated in mouse models of HIDS. Administration of ERK activators should be followed by serum quantification of cytokines, such as TNF and IL-1β. Quantification of IgM and IgD levels would allow proper evaluation of the here proposed hypothesis. Different regimen of administration should be performed for different periods of time (1-4 weeks). (PPTX 53 kb)

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Silva, R.C.M.C. Hyper-IgD Syndrome: Caused by Deficiency on Ras Prenylation and Trained Immunity?. J Clin Immunol 43, 1740–1742 (2023). https://doi.org/10.1007/s10875-023-01548-x

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