Furthermore, these patients are prone to pulmonary complications, gastrointestinal manifestations, autoimmune disorders, hematologic abnormalities, lymphoproloferation and malignancies.

In some cases, females with significant reduction in circulating lymphocytes carrying the CD40L mutation due to skewed X-chromosome inactivation can present with symptoms resembling HIGM1 or common variable immunodeficiency.

[7] IgM is the form of antibody that all B cells produce initially before they undergo class switching due to exposure to a recognized antigen.

Healthy B cells efficiently switch to other types of antibodies as needed to attack invading bacteria, viruses, and other pathogens.

CD40L-CD40 interaction is the first step in B cell stimulation for class switch recombination (CSR) and somatic hyper mutation (SHM) resulting in the generation of various Ig isotypes.

[1] The diagnosis of X-linked hyper IgM syndrome (HIGM1) is established in males with typical clinical and laboratory findings by identifying a hemizygous pathogenic variant in the CD40LG gene through molecular genetic testing.

[12] The diagnosis of hyper IgM syndrome can be done via the following methods and tests:[1] The primary goal is to address the underlying defect in CD40L or other gene mutations causing HIGM.