α4β7 Integrin expression and blockade in pediatric and young adult gastrointestinal graft‐versus‐host disease
| Autor: | Kelly E. Lake, Michael B. Jordan, Rebecca A. Marsh, Parinda A. Mehta, Adam Lane, Azada Ibrahimova, Vijaya Chaturvedi, Stella M. Davies, Erika Owsley, Kasiani C. Myers, Adam S. Nelson, Bridget Litts, Pooja Khandelwal |
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| Rok vydání: | 2021 |
| Předmět: |
Integrins
medicine.medical_specialty Graft vs Host Disease chemical and pharmacologic phenomena Gastroenterology Vedolizumab Memory T Cells Young Adult 03 medical and health sciences 0302 clinical medicine immune system diseases Internal medicine medicine Humans Young adult Child Adverse effect biology business.industry Hematopoietic Stem Cell Transplantation Hematopoietic stem cell Hematology medicine.disease Blockade surgical procedures operative medicine.anatomical_structure Graft-versus-host disease Oncology 030220 oncology & carcinogenesis Pediatrics Perinatology and Child Health biology.protein Steroids Antibody business CD8 030215 immunology medicine.drug |
| Zdroj: | Pediatric Blood & Cancer. 68 |
| ISSN: | 1545-5017 1545-5009 |
| DOI: | 10.1002/pbc.28968 |
| Popis: | Background We hypothesized that α4β7 integrin expression on effector memory T cells (TEMs) would be elevated in pediatric hematopoietic stem cell transplant (HSCT) patients before and at diagnosis of acute gastrointestinal graft-versus-host disease (GI GVHD) symptoms compared to patients without GVHD, and that clinical blockade of α4β7 integrin with vedolizumab would be effective in pediatric GI GVHD. Methods We analyzed surface expression of α4β7 integrin on T cells from 48 pediatric allogeneic HSCT recipients from our biorepository with known clinical outcomes as follows: acute GI GVHD (n = 22), isolated skin GVHD (n = 12), and no GVHD (n = 14). T-cell analyses were performed 1 week before and at GVHD diagnosis in patients with GVHD, and day +30 after HSCT in patients without GVHD. We describe clinical outcomes of seven additional patients, different from above-described 48 patients, who received vedolizumab (anti-α4β7 integrin antibody) for the treatment of steroid-refractory acute GI GVHD. Results Expression of α4β7 integrin on CD8+ TEMs was upregulated in patients with GI GVHD compared to the no GI GVHD (skin GVHD + no GVHD) group 1 week prior to clinical symptoms (p = .02) and at acute GI GVHD diagnosis (p = .05). Four of seven treated patients with clinical steroid-refractory acute GI GVHD were evaluable for response to vedolizumab. One patient had a complete response at day +28, while two had a partial response, and one had no response. No adverse effects directly attributable to vedolizumab were observed. Conclusion Our data suggest a rationale for the blockade of α4β7 integrin for acute GI GVHD management in children. |
| Databáze: | OpenAIRE |
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