The patient has difficulty in his immune response to both fungal (Candida) and bacterial (S. pneumonia) infections. This reflects a deficiency in both cell-mediated (T-cell) immunity and humoral (B-cell) immunity. Therefore, combined immunodeficiency is the most likely cause of this patient's symptoms.
In SCID, a deficiency in T-cells impairs both cell-mediated immunity (directly mediated by T-cells) and humoral immunity (deficiency of T-cells means helper function is also impaired). The most common cause of SCID is an X-linked defect leading to an impaired common gamma chain on cytokine receptors. Another cause of SCID is the cellular absence of adenosine deaminase. Both of these impairments lead to a deficiency of T-cells and a subsequent decrease in both cell-mediated and humoral immunity.
Punnoose et al. explore the diagnosis, treatment, and follow-up care of patients with SCID. SCID is often diagnosed as part of the newborn screen (blood test done at birth that checks for several diseases). Patients are often healthy at birth but later develop multiple and severe infections. Intravenous immunoglobulin and bone marrow transplants help protect and bolster the immune system.
Yao et al. retrospectively review the clinical manifestations, immunologic, and preliminary genetic features of those with SCID. Clinically, SCID patients often present with severe infections between 2 and 7 months old. An important diagnostic feature of SCID is lymphopenia. Twenty-five percent of their patient population (n=44) were found to have a mutation in IL2RG ( interleukin-2 receptor subunit gamma). Hematopoietic stem cell transplantation (HSCT) was the main treatment therapy in the study population.
Illustration A depicts an overview image of T-cell immunodeficiencies. Illustration B demonstrates the defective ILR2G protein that results in SCID. This receptor functions to sit in the plasma membrane of immune cells and allow communication between the B and T-cells. If defective, the immune cells are unable to communicate. leading to a suboptimal immune response to invasions.
Answer 1: X-linked agammaglobulinemia, also known as Bruton's agammaglobulinemia, results in an absence of B-cells and all immunoglobulins due to a defect in B-cell maturation. T-cell number and function are intact.
Answer 2: Isolated IgA deficiency patients are predisposed to recurrent sinopulmonary and gastrointestinal tract infections. This condition is associated with an anaphylactic response to transfused blood.
Answer 4: DiGeorge syndrome can be remembered by the mnemonic CATCH 22. Cleft lip, Abnormal facies, Thymic aplasia, Cardiac abnormalities, and Hypocalcemia. There is a deletion present on chromosome 22.
Answer 5: MHC class II deficiency is an inherited autosomal recessive trait that has a characteristic deficiency in CD4 T cells. It differs from SCID in that these patients still have T-cells that are able to respond to nonspecific T-cell mitogens.
Punnoose AR, Lynm C, Golub RM. JAMA patient page. Severe combined immunodeficiency. JAMA. 2013 Jan 2;309(1):98. doi: 10.1001/jama.2012.6226.
PMID:23280232 (Link to Abstract)
Yao CM, Han XH, Zhang YD, Zhang H, Jin YY, Cao RM, Wang X, Liu QH, Zhao W, Chen TX. Clinical characteristics and genetic profiles of 44 patients with severe combined immunodeficiency (SCID): report from Shanghai, China (2004-2011). J Clin Immunol. 2013 Apr;33(3):526-39.
PMID:23250629 (Link to Abstract)