Immunoglobulin replacement therapy, intravenously orsubcutaneously, is a lifesaving therapy for patients with severeantibody deficiency diseases and SCIDs. It provides passiveimmunity against common microorganisms and reduces thefrequency and severity of infection in most patients. Immunoglobulin replacement therapy is usually administered ata total monthly dose of 400 to 600 mg/kg of body weightadministered intravenously every 3 to 4 weeks, or subcutaneously by infusion pump every 1 to 2 weeks. IVIG therapyshould be monitored by regularly measuring trough immunoglobulin levels and, more important, the patient’s clinical course. Patients who continue to have recurrent infections, especially in the last week before the administration of IVIG,may require higher doses or more frequent administration.A combination of prophylactic antibiotics and immunoglobulin replacement therapy may be indicated in patientswho continue to have recurrent infections. Complications of IVIG therapy include transfusion reactions with chills,fever, and myalgias. They usually can be prevented in subsequent infusions by pretreatment with an antihistamine, anantipyretic, and by a slower rate of infusion. Headache fromaseptic meningitis can develop after IVIG therapy, usually inthe first 24 hours. It most often responds to treatment with ibuprofen. Allergic reactions to IVIG can occur in patientswith absent IgA. Allergic reactions are rare and should not occur in patients who have detectable serum IgA levels or patients who cannot synthesize any antibodies. Subcutaneous administration of immunoglobulin has fewer adverseeffects but may be complicated by local reactions at the site(s)of infusion. The risk of transmission of infectious agents,despite preparation from large numbers of selected donors,is extremely low.
Therapy for severe T-cell disorders is stem cell transplantation, preferably from a human leukocyte antigen–matchedsibling (see Chapter 76). Immunoglobulin replacement provides passive antibody-mediated immunity. Some patientscontinue to have poor B-cell function after stem cell transplantation and require lifelong immunoglobulin replacementtherapy. GVHD, in which the transplanted cells initiate animmune response against the host tissues, is the main complication of stem cell transplantation. Patients with the ADAdeficiency form of SCID who lack matched sibling donors canreceive repeated intramuscular replacement doses of ADA,stabilized by coupling to polyethylene glycol. Gene therapyhas been performed in several patients with common gammachain deficiency and ADA deficiency by transfer of a normalgene into bone marrow stem cells, which are infused into thepatient. Gene therapy for common gamma chain deficiencywas successful in most of the treated patients; however, itwas complicated by the development of leukemia in somepatients.
Population-based screening programs for SCID is underwaybecause early identification of SCID prior to infectious complications improves outcomes. Polymerase chain reaction amplification of T-cell receptor excision circles (TRECs) formed duringT-cell receptor recombination can be performed on newbornscreening blood spots to detect severe T-cell lymphopenia. Newborn screening for TRECs has been shown to detect SCID at birth,and this test has been recommended for universal screening.