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Background: The clinical significance and efficacy of treating patients who have immunoglobulin (Ig) G subclass deficiency and/or antibody deficiency with Ig-replacement therapy has been debated. There are no clear guidelines to recommend intravenous gammaglobulin (IgIV) in these patients as there are few published studies documenting its efficacy. Methods: We studied in an open-label protocol 10 adult patients with recurrent respiratory infections and IgG subclass and/or antibody deficiency. All patients received monthly IgIV for 12 months and then were observed for 3 months without IgIV infusions. We studied quality of life, incidence of infections, need for antibiotics, frequency of hospitalizations due to infections, IgG subclass and antibody (tetanus and pneumococcal) levels. Innate immunity was evaluated by studying the status of Toll-like receptors and polymorphisms, mannan-binding lectin levels and genotypes. Correction of the immune defects during IgIV therapy was evaluated. Results: Monthly IgIV significantly improved quality of life, decreased the number of infections and the need for antibiotics, and improved IgG subclass and antibody serum levels. No consistent finding of innate immunity could be detected. Conclusions: IgIV could be beneficial in patients with IgG subclass or antibody deficiency.

The major risk factor for developing systemic lupus erythematosus (SLE) is being female. The present study utilized gene profiles of activated T cells from females with SLE and healthy controls to identify signaling pathways uniquely regulated by estradiol that could contribute to SLE pathogenesis. Selected downstream pathway genes (+/- estradiol) were measured by real time polymerase chain amplification. Estradiol uniquely upregulated six pathways in SLE T cells that control T cell function including interferon-alpha signaling. Measurement of interferon-alpha pathway target gene expression revealed significant differences (p= 0.043) in DRIP150 (+/- estradiol) in SLE T cell samples while IFIT1 expression was bimodal and correlated moderately (r= 0.55) with disease activity. The results indicate that estradiol alters signaling pathways in activated SLE T cells that control T cell function. Differential expression of transcriptional coactivators could influence estrogen-dependent gene regulation in T cell signaling and contribute to SLE onset and disease pathogenesis.

Estrogen plays a role in the activation of systemic lupus erythematosus (SLE) and in upregulating intracellular signals by binding to the estrogen receptor(s). Fulvestrant (Faslodex, AstraZeneca Pharmaceuticals, Wilmington, DE, USA), an estrogen selective receptor downregulator, competes for receptor binding in vitro and inhibits estrogen action in target cells. We evaluated the efficacy, side effects, and expression of T cell activation markers, following the administration of fulvestrant or placebo to premenopausal patients with SLE.Twenty women with moderate SLE Disease Activity Index (SLEDAI; 7.87 +/- 3.7) were enrolled. They were premenopausal with regular menstrual cycles and not taking exogenous hormones. The study was double-blind and placebo-controlled. Ten patients received 250 mg fulvestrant intramuscularly for 12 months, and 10 received the placebo. All were observed monthly and 3 months after final fulvestrant/placebo injection. Measures studied were monthly SLEDAI scores, routine and serologic markers for lupus, and serum concentrations of estrogen and fulvestrant. Expression of T cell calcineurin and CD154 mRNA in peripheral T cells was measured by polymerase chain reaction. Medications the patients were taking were recorded each visit. Bone density was obtained at baseline and at visit 12.Sixteen patients completed the 15-month study, 8 from each group. SLEDAI improved significantly in the fulvestrant group at both 12 months (p = 0.02) and 15 months (p = 0.002), but serologic markers, routine laboratory tests, and bone density did not. Serum estrogen levels were higher in the fulvestrant group and dropped when fulvestrant was discontinued; these differences were not statistically significant. Medications for therapy of lupus to the fulvestrant group were reduced, whereas the placebo group medications were unchanged or increased. Comparison of relative values at individual timepoints revealed significantly lower median values for the T cell activation markers CD154 (p0.001) and calcineurin (p = 0.013) in the fulvestrant arm.Blocking estrogen receptors in vivo by an estrogen selective receptor downregulator could be considered as a new and relatively safe therapeutic approach in the management of SLE patients with moderately active disease for the 1-year study period.