Recombinant interleukin 2 therapy in severe combined immunodeficiency disease.
Severe combined immunodeficiency disease (SCID) is a congenital disorder of severe B- and T-lymphocyte dysfunction in which several pathogenic mechanisms have been identified. The present study describes a female child with SCID who had a primary defect in the ability of T cells to secrete interleukin 2 (IL-2). B- and T-cell numbers were normal, but their functions were severely deficient. Mitogen and antigen-driven lymphoproliferative responses were diminished but were correctable in vitro with recombinant IL-2 (rIL-2). The patient's phytohemagglutinin-stimulated lymphocytes expressed IL-2 receptors normally. Despite the presence of the gene for IL-2, the patient's cells were grossly deficient in messenger RNA for IL-2 and endogenous IL-2 production. Pokeweed mitogen-driven B-cell differentiation was decreased and was not corrected by the addition of normal T cells to the B cells. Two attempts at immune reconstitution by haploidentical bone marrow transplantation failed. Therapy with rIL-2 (30,000 units/kg, given daily i.v.) resulted in marked clinical improvement as well in improved T-cell functions. The child, now 3 yr old, has been on rIL-2 therapy for 2 yr and receives rIL-2 (30,000 units/kg) three times weekly at home. This case study points to a new direction in the treatment of such disorders with rIL-2.
Pahwa
R
R
Department of Pediatrics, Schneider Children's Hospital of Long Island Jewish Medical Center, New Hyde Park, NY 11042.
Chatila
T
T
Pahwa
S
S
Paradise
C
C
Day
N K
NK
Geha
R
R
Schwartz
S A
SA
Slade
H
H
Oyaizu
N
N
Good
R A
RA
D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000188:drug therapy* / Q000276:immunology; D007223:Infant; D007376:Interleukin-2 / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012016:Reference Values; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology
D007376:Interleukin-2; D011994:Recombinant Proteins