We report an atypical case of complete DiGeorge (DG) anomaly that presented initially exclusively as severe combined immunodeficiency (SCID). The child had severe infections at diagnosis, in keeping ...with the SCID phenotype; however, normal lymphocyte counts and immunoglobulin levels were noted at admission, which delayed diagnosis. Importantly, the child presented without neonatal hypocalcemia or velofacial or cardiac abnormalities at the time of diagnosis, which masked underlying DG. This case outlines the difficulties in making the diagnosis of SCID in a timely manner and illustrates the variation in presentation of the 22q11.2 deletion syndrome. There should be a high index of suspicion for primary immunodeficiency among children with severe infections and, because management may vary, DG anomaly should be considered in the differential diagnosis of T- B+ natural killer+ SCID.
Intravenous immunoglobulin (IVIG) has become an accepted mode of therapy in immune diseases with the potential to act as an immune enhancer or immunomodulator. A 14-year-old girl with severe ...steroid-dependent asthma was enrolled in a trial of high dose intravenous immunoglobulin because of the unremitting nature of her illness and severe steroid side effects. She received 2 g/kg of IVIG every month for six months. In the 4 months preceding IVIG therapy she had repeated exacerbations of her asthma. In contrast, during the 6 months of IVIG therapy, she only had one exacerbation of her asthma. Her steroid dose was tapered by 75% and her FEV1 improved by 100%. To detect alterations in immune reactivity, we monitored serial skin tests to an individualized panel of antigens, RAST tests to the same panel, and specific IgG levels. Serial titrations of her prick skin tests showed a 2-3 log increase in threshold for skin reactivity to all five antigens on her panel. In parallel, RAST results to the same antigen panel showed a decrease in specific IgE production. The significant clinical improvement and steroid reduction in this patient appear due, at least in part, to the immunomodulatory effects of high dose IVIG therapy.
Background: Intravenous immunoglobulin (IVIG) has been used extensively in the treatment of autoimmune and allergic diseases, but the precise mechanism behind its efficacy remains unclear. Ligation ...of the low-affinity IgG Fc receptor FcγRIIb can inhibit B-lymphocyte activation. Our laboratory has shown that IVIG suppresses proliferation and IgE production by human B cells stimulated with IL-4 and anti-CD40 antibodies.Objective: We sought to determine whether the regulatory action of IVIG is mediated through binding FcγRIIb, phosphorylation of the receptor, and induction of phosphatases, including SH2-containing inositol-5'-phosphatase.Methods: All experiments were performed on human tonsillar B cells. Phenotyping was performed by means of flow cytometry. Cells were cultured with IL-4 and anti-CD40 antibodies with or without IVIG (10 mg/mL), and FCγRIIb receptor activation and phosphorylation were measured by means of Western blot analysis.Results: FcγRIIb was the predominant isoform of Fcγ receptor expressed on tonsillar B cells, and preincubation with IVIG failed to block binding of FcγRIIb antibody. Anti-FcγRIIb antibodies did not reverse inhibition of B-cell proliferation or IgE production by IVIG. Treatment of stimulated B lymphocytes with IVIG for 1 to 60 minutes did not change the global protein tyrosine phosphorylation pattern, except for tyrosine phosphorylation of an unidentified 30-kd protein. We directly examined tyrosine phosphorylation of FcγRIIb and its downstream-associated phosphatase, SH2-containing inositol-5'-phosphatase. Both remained unchanged after IVIG treatment, as did other related phosphatases.Conclusion: These data argue against the involvement of FcγRIIb in the inhibition of CD40/IL-4-induced B-cell activation by IVIG. (J Allergy Clin Immunol 2002;110:480-3.)
Intravenous immunoglobulin (IVIG) has been used extensively in the treatment of autoimmune and allergic diseases, but the precise mechanism behind its efficacy remains unclear. Ligation of the ...low-affinity IgG Fc receptor FcgammaRIIb can inhibit B-lymphocyte activation. Our laboratory has shown that IVIG suppresses proliferation and IgE production by human B cells stimulated with IL-4 and anti-CD40 antibodies.
We sought to determine whether the regulatory action of IVIG is mediated through binding FcgammaRIIb, phosphorylation of the receptor, and induction of phosphatases, including SH2-containing inositol-5'-phosphatase.
All experiments were performed on human tonsillar B cells. Phenotyping was performed by means of flow cytometry. Cells were cultured with IL-4 and anti-CD40 antibodies with or without IVIG (10 mg/mL), and FCgammaRIIb receptor activation and phosphorylation were measured by means of Western blot analysis.
FcgammaRIIb was the predominant isoform of Fcgamma receptor expressed on tonsillar B cells, and preincubation with IVIG failed to block binding of FcgammaRIIb antibody. Anti-FcgammaRIIb antibodies did not reverse inhibition of B-cell proliferation or IgE production by IVIG. Treatment of stimulated B lymphocytes with IVIG for 1 to 60 minutes did not change the global protein tyrosine phosphorylation pattern, except for tyrosine phosphorylation of an unidentified 30-kd protein. We directly examined tyrosine phosphorylation of FcgammaRIIb and its downstream-associated phosphatase, SH2-containing inositol-5'-phosphatase. Both remained unchanged after IVIG treatment, as did other related phosphatases.
These data argue against the involvement of FcgammaRIIb in the inhibition of CD40/IL-4-induced B-cell activation by IVIG.
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