IRAK4 Deficiency & MyD88 Deficiency
IRAK4 deficiency and MyD88 deficiency - Patients can develop invasive Streptococcus infections (cellulitis, sepsis, meningitis, osteomyelitis). This is the primary organism causing disease in patients followed by Staph aureus. These patients fail to manifest signs of inflammation (fevers, elevated CRP or ESR) despite having deep-seated infections.
NEMO or IKBA deficiency - Patients can develop infections with gram positive and gram negative pyogenic bacteria as well as mycobacteria. Innate signaling through toll-like receptors and CD40-CD40L signaling is impaired.
Asplenia - Primary or secondary asplenia is associated with an increased risk of disseminated infections with encapsulated bacteria (S. pneumoniae, H. influenzae, and N. meningitides). The spleen plays a key role in the phagocytosis and clearance of non-opsonized bacteria.
Classical Complement Deficiency
Early classical complement component deficiencies - Patients increased risk of developing invasive infections with encapsulated bacteria such as S. pneumoniae. The complement fragment C3b acts as one of the main opsonins that facilitate microbial phagocytosis. Patients also have increased risk of developing immune complex disease (SLE).
Antibody deficiencies such as CVID, XLA and AR HIGM are associated with recurrent sinopulmonary infections with encapsulated bacteria. The clearance of encapsulated bacteria is greatly enhanced by opsonization with antibodies.