Synergistic Effect of Steroids and Intravenous Immune Globulin (Ivig) in a Patient With Autoimmune Neutro Penia (Ain)

Abstract

IVIG has been used to treat AIN, but it is not always effective. We report a patient in which the concommitant use of IVIG and steroid was more effective than either alone. A 10 year old girl with neutropenia and anti-neutrophil antibodies had chronic gingivitis, buccal erosions, and staphylocca skinabsces-4 ses. Absolute neutrophil counts (ANC) were 40-400/mm . IVIG at 2 gmlkg had no effect. She later developed fever, anorexia, and abdominal pain due to bacterial ileitis. Antibiotics alone gaveonly partial clinical improvement. The addition of Solumedrol, lmglkgl day, transiently raised the ANC from 100 to 3500. The ANC subsequently declined to <loo, with clinical relapse, while on thesame steroid dose. Adding 1 gmlkglday IVIG X 3 raised the ANC to 2400 in 2 daysand to 11000 in 6 days. This allowed resection of the infected ileum without complications. The ANC remained >I000 for 30 days. Subsequently, while on 40120 mg alternate day prednisone, 4 infusions of 1 gmlkg IVIG over 7 days did not raise the ANC. Increasing the steroids to 45 mglday (1 mglkg) promptly increased the ANC from 800 to 9700 without further IVIG. Ten monthly lgmlkg infusions of IVIG have kept her infection-free by maintaining ANC >500, although anti-neutrophil antibodies continue to be present. As prednisone was tapered and discontinued, the ANC response to each course of IVIG decreased. Optimization of prednisone dose in relation to the IVIG infusions is in progress. Our observations suggest that IVIG and steroids may act synergistically to decrease peripheral destruction of antibody sensitized blood cells. WAS is an X-linked disorder characterized by immune deficiency, thrombocytopenia and eczema. Previous studies of G-6-PD isozyne expression in rare females doubly heterozygous for WAS and G-6-PO found one of two X chromosomes to be preferentially active in T cells and platelets compared to their fibroblasts. Presumably this is due to selection against cells in which the X chromosome with the WAS allele is active. We have used a new strategy that distinguishes the active and inactive X chromosomes for the detection of WAS carriers. Genomic DNA is analyzed by Southern blot to detect heterozygosity for X chromosome restriction fragment length polqmorphisms (RFLP) at the P6K or HGPRT loci. For both loci, the state of methylation is different and constant between the active and inactive X chromosomes. In females heterozygous for these RFLP1s the active and inacttve X's can thus be distinguished with with methylation-sensitive restriction endonucleases. We have screened 32 female relatives of WAS patients: 14 were heterozygous at one of the two loci (44% potential1 y informative). CLINICAL AND IMMUNOLOGIC FEATURES OF PEDIATRIC AIDS-RELATED FOMPLEX (PARC).The methylation pattern of DNA from T cells of non-carriers showed random X-inactivation. In contrast, DNA from T cells of WAS carriers showed only one of the two X chromosomes to be active. Thus. X-inactivation analysis appears to dl rectl y identify WAS carriers and does not require the rare...