SIR—Mannon et al. [1] reported a promising treatment of Crohn disease with anti–IL-12p40 antibody in a recent issue of the New England Journal of Medicine. This treatment had response and remission rates of 75% and 38%, respectively. Decreases in IL-12 and IFN-γ levels and TNF-α production by lamina propria mononuclear cells were documented but were not correlated with clinical response. Surprisingly, the authors did not discuss the possible risk of mycobacteriosis and salmonellosis in patients receiving anti-IL-12p40–specific antibody.

Patients with autosomal recessive complete deficiency of the p40 subunit of IL-12 (which is shared by IL-23) or the β1 chain of the IL-12/IL-23 receptor have impaired IL-12– and IL-23–dependent IFN-γ–mediated immunity. These patients have clinical disease caused by weakly virulent mycobacteria (i.e., bacille Calmette-Guérin substrains and environmental species) and nontyphoid Salmonella species and have severe forms of tuberculosis [2]. Since the first description in 1998 of inherited disorders associated with IL-12p40 and IL-12Rβ1 deficiency, the number of patients for whom these conditions were diagnosed has steadily increased, providing invaluable clinical information [3, 4]. These inherited conditions are mimicked in patients who are receiving anti–IL-12p40 antibody treatment.

Patients with Crohn disease who were treated with anti–TNF-α antibody were found to be at risk for reactivation of latent tuberculosis—an unexpected complication, given that no heritable disease associated with TNF-α–mediated immunity in humans was known at the start of clinical trials. Because these infections frequently induce intestinal manifestations, which may remain unrecognized in patients with Crohn disease, we wish to draw attention to the high risk of severe disease caused by even weakly virulent salmonellae or mycobacteria in patients with Crohn disease treated with anti–IL-12p40 antibody [5].

Acknowledgments

Potential conflicts of interest. All authors: no conflicts.

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