Clinical outcome in IL-10- and IL-10 receptor-deficient patients with or without hematopoietic stem cell transplantation

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• 作者：Karin R. Engelhardt ; PhD^a ; ^b ; Neil Shah ; MD^c ; Intan Faizura-Yeop ; MD^c ; Dilara F. Kocacik Uygun ; MD^d ; Natalie Frede^b ; Aleixo M. Muise ; MD ; PhD^e ; ^f ; Eyal Shteyer ; MD^g ; Serkan Filiz ; MD^d ; Ronnie Chee ; MD^a ; Mamoun Elawad ; MD^c ; Britta Hartmann ; PhD^h ; Peter D. Arkwright ; MD ; PhDⁱ ; Christopher Dvorak ; MD^j ; Christoph Klein ; MD ; PhD^k ; Jennifer M. Puck ; MD^j ; Bodo Grimbacher ; MD^a ; ^b ; Erik-Oliver Glocker ; MD^l ; ^{erik-oliver.glocker@uniklinik-freiburg.de}
• 关键词：IL-10 ; IL-10 receptor ; enterocolitis ; mutations ; colectomy ; hematopoietic stem cell transplantation
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2013
• 出版时间：March, 2013
• 年：2013
• 卷：131
• 期：3
• 页码：825-830.e9
• 全文大小：861 K

文摘

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Background

Inherited deficiencies of IL-10 or IL-10 receptor (IL-10R) lead to immune dysregulation with life-threatening early-onset enterocolitis.

Objectives

We sought to gather clinical data of IL-10/IL-10R-deficient patients and devise guidelines for diagnosis and management, including hematopoietic stem cell transplantation (HSCT).

Methods

We enrolled 40 patients with early-onset enterocolitis and screened for mutations in IL10/IL10R using genetic studies, functional studies, or both of the IL-10 signaling pathway. Medical records of IL-10/IL-10R-deficient patients were reviewed and compiled.

Results

Of 40 patients, we identified 7 with novel mutations, predominantly in consanguineous families with more than 1 affected member. IL-10/IL-10R-deficient patients had intractable enterocolitis, perianal disease, and fistula formation. HSCT was carried out in 2 patients with IL-10 deficiency and 1 patient with IL-10R ¦Á chain deficiency and proved to be an effective therapy, leading to rapid improvement of clinical symptoms and quality of life.

Conclusion

Because the defect in patients with IL-10/IL-10R deficiency resides in hematopoietic lineage cells and their colitis is resistant to standard immunosuppressive therapy, HSCT should be considered early as a potentially curative therapeutic option.