Letters to the Editor
Natalizumab to kill two birds with one stone: A case of celiac disease and multiple sclerosis
Article first published online: 6 APR 2011
Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 17, Issue 6, pages E62–E63, June 2011
How to Cite
Phan-Ba, R., Lambinet, N., Louis, E., Delvenne, P., Tshibanda, L., Boverie, J., Moonen, G. and Belachew, S. (2011), Natalizumab to kill two birds with one stone: A case of celiac disease and multiple sclerosis. Inflamm Bowel Dis, 17: E62–E63. doi: 10.1002/ibd.21716
- Issue published online: 10 MAY 2011
- Article first published online: 6 APR 2011
To the Editor:
We report the unusual course of celiac disease associated with multiple sclerosis (MS). A patient who received natalizumab because of an interferon β1-resistant MS completely recovered from chronic digestive symptoms that proved to be due to celiac disease.
A 28-year-old woman was diagnosed with relapsing/remitting MS 5 years earlier, gradually exacerbated chronic diarrhea, post-meal abdominal cramps, and insidious weight loss during the last year. At that time she was treated for 4 years with interferon β1b 250 μg subcutaneously every other day and experienced her fifth MS relapse with a Lhermitte sign and hypoesthesia of the four limbs below a C4 level. A new gadolinium-enhancing cervical cord lesion was demonstrated and she received intravenous steroid pulses with a partial recovery. Two months later a brain magnetic resonance imaging (MRI) scan showed an increase of the total T2 lesion load (Fig. 1A–C) with one inflammatory lesion in the right frontal juxtaventricular region (Fig. 1A,B).
She had lost 8 kg in the last 4 months without changing her diet. Gastroenterological investigations were then begun. A double contrast barium enema was performed and provided evidence of a near complete loss of duodenal folds (Fig. 1D). Besides this indirect sign of duodenal atrophy, the number and thickness of the folds in the ileum were increased (data not shown). Blood tests revealed an iron deficiency without anemia, high titers of anti-gliadin (IgG and IgA), and positive anti-endomysium antibodies. The duodenal biopsy finally demonstrated a moderate to severe villous atrophy (Fig. 1E), associated with a massive intraepithelial infiltration by CD3-expressing T lymphocytes (Fig. 1F). We diagnosed adult celiac disease.
Based on the clinical and radiological activity of her MS condition, it was decided to stop interferon β1b immunomodulatory treatment and switch to natalizumab as monotherapy (300 mg intravenously every 4 weeks, TYSABRI) in order to halt relapses and reduce neurological disability progression. The week immediately after the first dose of natalizumab her diarrhea and post-meal pain completely vanished. Three months later, after 3 doses of natalizumab she remained diarrhea- and pain-free and had regained 7 kg with no specific diet. However, mild abdominal cramps resumed after 5 months of natalizumab. A control biopsy then showed recurrent histological signs of celiac disease and a gluten-free diet had to be undertaken.
Natalizumab is a humanized monoclonal immunoglobulin G4 directed against α4 integrins. In the present case, the induction of α4 integrin blockade by natalizumab matched a rapid-onset and drastic, but transient, clinical remission of concurrent celiac disease. This remission occurred with no specific change in the diet while the patient continued to be exposed to daily intake of gluten-containing products.
The α4 integrin protein dimerizes either with the β1 or β7 subunits. The therapeutic effect of natalizumab is mediated by the ability to block the binding of α4β1 and α4β7 complexes expressed by lymphocytes to their respective endothelial receptors, vascular-cell adhesion molecule 1 (VCAM-1), and mucosal addressin-cell adhesion molecule 1 (MAdCAM-1). These molecular interactions are required for lymphocytes to enter the central nervous system (mediated by α4β1 and VCAM-1) and the intestine (mediated by α4β7 and MAdCAM-1). Previous studies have shown that natalizumab is effective as induction therapy for patients with moderate to severely active Crohn's disease,1–3 but nothing is known about the potential effect of this antibody in celiac disease. It is established that gliadin epitope specific T cells induced in peripheral blood after a gluten challenge in celiac disease patients express the intestinal homing integrin α4β7.4, 5 Hence, the present observation emphasizes that the α4 chain of α4β7 complex may play a crucial role in the pathogenesis of T-cell intraepithelial infiltration of the duodenum in celiac disease. Such a case paves the way for new therapeutic avenues6 in severe or gluten-free diet refractory celiac disease and sheds new light on the understanding of this enteropathy.
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- 2Natalizumab for active Crohn's disease. N Engl J Med. 2003; 348: 24–32., , , et al.
- 3Natalizumab induction and maintenance therapy for Crohn's disease. N Engl J Med. 2005; 353: 1912–1925., , , et al.
- 4Characterizing the circulating, gliadin-specific CD4+ memory T cells in patients with celiac disease: linkage between memory function, gut homing and Th1 polarization. J Leukoc Biol. 2006; 79: 676–685., , , et al.
- 5T cells in peripheral blood after gluten challenge in coeliac disease. Gut. 2005; 54: 1217–1223., , , et al.
- 6Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet. 2007; 369: 1641–1657., .
Rémy Phan-Ba MD* **, Nadine Lambinet MD* **, Edouard Louis MD, PhD* **, Philippe Delvenne MD, PhD* § **, Luaba Tshibanda MD* ¶ **, Jacques Boverie MD* ¶ **, Gustave Moonen MD, PhD* **, Shibeshih Belachew MD, PhD* **, * MYelin Disorders REsearch teAM (MYDREAM), C.H.U. de Liège University of Liège Liège, Belgium, Department of Neurology C.H.U. de Liège University of Liège Liège, Belgium, Department of Gastroenterology C.H.U. de Liège University of Liège Liège, Belgium, § Department of Medical Imaging C.H.U. de Liège University of Liège Liège, Belgium, ¶ Department of Pathology C.H.U. de Liège University of Liège Liège, Belgium, ** Department of Neurology C.H.U. de Liège University of Liège Liège, Belgium.