The relationship between the use of tumor necrosis factor antagonists and onset of granulomatous infection was examined using data collected through the Adverse Event Reporting System of the US Food and Drug Administration for January 1998-September 2002. Granulomatous infections were reported at rates of approximately 239 per 100,000 patients who received infliximab and approximately 74 per 100,000 patients who received etanercept (P<.001). Tuberculosis was the most frequently reported disease, occurring in approximately 144 and approximately 35 per 100,000 infliximab-treated and etanercept-treated patients, respectively (P<.001). Candidiasis, coccidioidomycosis, histoplasmosis, listeriosis, nocardiosis, and infections due to nontuberculous mycobacteria were reported with significantly greater frequency among infliximab-treated patients. Seventy-two percent of these infection occurred < or =90 days after starting infliximab treatment, and 28% occurred after starting etanercept treatment (P<.001). These data indicate a risk of granulomatous infection that was 3.25-fold greater among patients who received infliximab than among those who received etanercept. The clustering of reports shortly after initiation of treatment with infliximab is consistent with reactivation of latent infection.

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The tubular gland of the chicken oviduct is an attractive system for protein expression as large quantities of proteins are deposited in the egg, the production of eggs is easily scalable and good manufacturing practices for therapeutics from eggs have been established. Here we examined the ability of upstream and downstream DNA sequences of ovalbumin, a protein produced exclusively in very high quantities in chicken egg white, to drive tissue-specific expression of human mAb in chicken eggs. To accommodate these large regulatory regions, we established and transfected lines of chicken embryonic stem (cES) cells and formed chimeras that express mAb from cES cell-derived tubular gland cells. Eggs from high-grade chimeras contained up to 3 mg of mAb that possesses enhanced antibody-dependent cellular cytotoxicity (ADCC), nonantigenic glycosylation, acceptable half-life, excellent antigen recognition and good rates of internalization.

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