Combined B-Cell and T-Cell Disorders Medication
- Author: Francisco J Hernandez-Ilizaliturri, MD; Chief Editor: Emmanuel C Besa, MD more...
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Blood products/immunoglobulins provide immediate passive immunity. These agents can be used as replacement therapy in patients with antibody-deficiency states.
Provide an immediate rise of antibodies that have a proven protective effect against bacterial and viral infection (passive immunity). Because antibodies are not produced by the host, these products must be readministered monthly. This treatment may increase CSF IgG (10%).
Metabolic enzymes are used to replace ADA.
ADA is an enzyme of the purine salvage pathway that is responsible for adenosine and deoxyadenosine deamination to inosine and deoxyinosine, respectively. ADA deficiency leads to accumulation of the metabolites dATP and 2'-deoxyadenosine, both of which are toxic to lymphocytes.
Treatment is indicated in patients with SCID secondary to ADA deficiency whose conditions proved refractory to bone marrow transplantation or who are not candidates for transplantation. Individualize therapy (based on plasma levels) to achieve the following: trough plasma levels of 15-35 mmol/h/mL and a decline in erythrocyte dATP to < 0.005-0.015 mmol/mL packed erythrocytes or to < 1% of total erythrocyte adenine nucleotide content (ATP + dATP). Plasma levels >35 mmol/h/mL are not associated with additional clinical benefit. This treatment has no role in preparatory regimen for bone marrow transplantation.
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|Pathophysiology||Cells Affected||Inheritance||Genes Involved|
|Premature cell death||T, B, NK||AR||ADA|
|Defective cytokine–dependent survival signaling||T, NK||AR
γ c type-XL
|JAK3, IL7RA (T cells only), γ c|
|Defective V(D)J rearrangement||T, B||AR||RAG1, RAG2, Artemis|
|Defective pre-TCR and TCR signaling||T||AR||CD3 δ, CD3 ζ, CD3 ε,
|AR = autosomal recessive; JAK3 =Janus tyrosine kinase 3; RAG1, RAG2 = recombinase activating gene 1 and 2, respectively; TCR = T-cell receptor; XL = X-linked; V(D)J = variable diversity joining.|