Infliximab Drives Gamma-Delta T Cell Expansion In Crohn's Disease – a Predictor of Lymphoma Risk?

Due to the widespread use of combined immunosuppressive therapy in the management of Crohn's disease (CD), the risk of malignant lymphoproliferation, including the fatal hepato-splenic T cell lymphoma (HSTCL), has become a major concern. We investigated dynamic changes of peripheral gamma-delta (γδ)-T cells during CD treatment with the anti-TNF-α-antibodies infliximab (Remicade^®) and adalimumab (Humira^®).

Forty-six patients with active CD and nine healthy volunteers were analysed. Patients delivered blood samples before and 1, 7, and 42 days after infliximab 5 mg/kg (20 patients) or adalimumab given as induction with 160 mg and 80 mg after 2 weeks and subsequently 40 mg every other week (26 patients). The γδ-T cells were analysed using FACS analysis. Patients with high percentages of peripheral γδ-T cells were characterized by PCR-assessment of γδ-T cell clonality.

Of 46 patients included in the analysis, 35 (76%) had γδ-T cell levels comparable to those of healthy individuals (mean: 1.6%; 95% CI: 1.3–2.0%). Higher γδ-T cell levels from 5% up to 15% occurred in 11 patients (24% of the total cohort). A high γδ-T cell level was associated with non-smoker status and young age. In 18 patients receiving thiopurines or methotrexate, the mean baseline γδ-T cell percentage was 4.4% (95% CI: 2.1–6.7%). In three male CD patients with high baseline values, the γδ-T cell percentage doubled within 24 hours following infliximab therapy. Another male patient on infliximab monotherapy presented with a predominantly clonal baseline γδ-T cell population as high as 20%, further increasing to 25% shortly after infliximab treatment.

One fourth of the CD patients treated with immunomodulators had constitutive high levels of circulating γδ-T cells, and infliximab aggravates this γδ-T cell expansion. We raise the hypothesis that such patients may be at increased risk of developing a malignant γδ-T cell lymphoproliferation.

No relevant conflicts of interest to declare.