Trained Immunity: A Preventive Strategy for Recurrent Infectious Diseases on SIgMD Phenotype with Potential Impact on Immune Functions

Recurrent infections occur in more than 80% of patients with SIGMD. Some of these bacterial infections may result in serious life-threatening infections. The clinical infectious presentations of SIGMD include recurrent otitis media, chronic sinusitis, bronchitis, bronchiectasis, pneumonia, urinary tract infections, cellulitis, meningitis, sepsis, etc. Some of the most common microbial organisms include Streptococcus pneumoniae, Hemophilus influenzae, Neisseria meningitidis, Pseudomonas aeruginosa, Aspergillus fumigatus, Giardia lamblia; many of these organism’s express epitopes of phosphorylcholine in their cell walls that are similar to those expressed on apoptotic cells, and recognized by natural IgM.

IgM is the first immunoglobulin to be expressed on the surface of B cells and the first immunoglobulin isotype secreted during an initial immune response to an exogenous antigen. Mature naïve B cells in response to antigens undergo clonal expansion and differentiation into Igsecreting cells. A subset of activated IgM⁺ B cells undergo a process of heavy chain isotype switching resulting in the production of antibodies of different isotypes such as IgG, IgA, and IgE, upon engagement of CD40 with CD40L and interaction with cytokines, and somatic hyper mutation in V region results in the selection of high affinity antibody producing B cells.

In contrast to secreted IgG, IgM comes in two ways, preimmune or without exposure to exogenous antigen also known as “natural IgM” that is spontaneously produced, and the second type is exogenous antigen-induced or “immune” IgM antibodies. In addition to providing early defense against microbes, natural IgM plays an important role in immune homeostasis, and provide protection from consequences of infections and inflammation .

The aim of this study is to promote immunomodulation homeostasis on SIGMd phenotypes and its comorbidities.

This trained immunity approach uses Vitamin D and β- glucan injectable immunostimulants protocols. β-glucan have an important role in Trained Immunity immunostimulants as they enhance innate and adaptive responses to bystander pathogens of adaptive immune cells, increasing the nonspecific effector response of innate immune cells, harnessing the activation state of dendritic cells to enhance adaptive T cell responses that enables longlived protection against specific and broader spectrum of and nonrelated pathogens.

Vitamin D has furthermore benefits then calcium homeostasis and bone mineralization and has become recognized as a pluripotent immunoregulator of biological functions with a particular role in immune tolerance and antimicrobial immunity. The expression of the Vitamin D. Receptor (VDR) in many immune cells has led to recognition of the associations between the D.vit. metabolism and infections, allergic and chronic auto-immune disorders.

Thus the activation and degranulation of inflammatory products that cause various clinical manifestations are minimized and regulated, with the consequent clinical improvement and no adverse effects.

Author(s): Fabrício Prado Monteiro

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