ABSTRACT
A doença enxerto contra hospedeiro (GVHD) é uma complicação comum nos pacientes submetidos ao transplante de células-tronco hematopoiéticas (TCTH), sendo considerada a maior causa de morbidade e mortalidade nesses pacientes. O principal objetivo do presente estudo foi relacionar a concentração de células de Langerhans em mucosa bucal de pacientes com GVHDc bucal com a expressão da quimiocina CCL20 e de seu receptor CCR6 no epitélio bucal, a fim de elucidar os mecanismos biológicos envolvidos no recrutamento das células de Langerhans na GVHDc. Foram selecionados fragmentos obtidos por biópsia de mucosa bucal de 60 pacientes onco-hematológicos e hematológicos submetidos previamente ao transplante de células tronco hematopoiéticas no Hospital Amaral Carvalho, Jaú SP, onde 30 pacientes desenvolveram GVHDc em mucosa bucal (Grupo 1) e 30 não desenvolveram GVHDc (Grupo 2). Amostras obtidas a partir de 30 biópsias de lesões não inflamatórias em mucosa bucal constituíram o Grupo Controle (Grupo 3). Cortes microscópicos foram avaliados em coloração de rotina Hematoxilina e Eosina, e submetidos à técnica imuno-histoquímica, utilizando-se anticorpos monoclonais anti-CD1a e anti-CCR6, e anticorpos policlonais anti-CCL20. As células de Langerhans CD1a+ foram quantificadas no epitélio da mucosa bucal, e os resultados demonstraram um maior número destas células nos pacientes com GVHDc quando comparados àqueles sem GVHDc e ao Grupo Controle (p<0,001). A análise da imunomarcação das moléculas CCR6 e CCL20 foi subjetiva com aplicação de escores. Quanto à molécula CCR6, houve maior expressão no Grupo 1 (p<0,001) em comparação aos outros Grupos; porém, quanto à expressão de CCL20, não houve diferença estatística entre os três Grupos (p=0,108). Estes resultados sugerem que o aumento das células de Langerhans, na doença enxerto contra hospedeiro crônica, em mucosa bucal, pode estar associado a maior expressão do receptor CCR6. Possivelmente, o maior recrutamento de células de...
The graft versus host disease (GVHD) is a common complication in patients undergoing hematopoietic stem cell transplantation (HSCT), and considered a major cause of morbidity and mortality in these patients. The main objective of this study was to compare the concentration of Langerhans cells in oral mucosa of patients with oral chronic GVHD (GVHDc) with the expression of the chemokine CCL20 and its receptor CCR6 in oral epithelium, in order to clarify the biological mechanisms involved in the recruitment of Langerhans cells in GVHDc. We selected 60 biopsies of oral mucosa from onco-hematological and hematological patients submitted to prior hematopoietic stem cell transplantation at Hospital Amaral Carvalho, Jaú - SP from which 30 patients developed GVHDc in the oral mucosa (Group 1) and 30 did not develop GVHDc (Group 2). The Control Group (Group 3) was obtained from 30 biopsies of non-inflammatory lesions of oral mucosa. Microscopic sections were evaluated in routine Hematoxylin and Eosin staining, and submitted to immunohistochemistry using anti-CD1a and anti-CCR6 monoclonal antibodies, and anti-CCL20 polyclonal antibody. The Langerhans cells (CD1a+) were quantified in the epithelium of the oral mucosa, and the results showed a greater number of these cells in patients with GVHDc compared to those without GVHDc and the Control Group (p<0.001). Analysis of immunostaining of molecules CCL20 and CCR6 were subjective with application of scores. The expression of CCR6 molecule was more significant in Group 1 (p<0.001) compared to other groups, but in relation to CCL20 expression, there was no statistical difference between the three groups (p=0.108). These results suggest that the increase of Langerhans cells in GVHDc affecting oral mucosa may be associated with increased expression of the receptor CCR6. We suggest that the increased recruitment of Langerhans cells to the oral mucosa in patients with transplanted bone marrow contributes...
Subject(s)
Humans , Male , Female , Adult , Langerhans Cells/pathology , Graft vs Host Disease/pathology , Mouth Mucosa/pathology , Chemokines/biosynthesis , /biosynthesis , Biopsy , Graft vs Host Disease/metabolism , Biomarkers/metabolism , Mouth Mucosa/metabolism , Sex Distribution , Statistics, Nonparametric , Hematopoietic Stem Cell Transplantation/adverse effectsABSTRACT
BACKGROUND: The Langerhans cells (LCs) are scattered throughout the epithelium of skin and mucosa and have been associated with the graft-vs.-host disease (GVHD), which is the highest cause of morbidity and mortality in patients who underwent bone marrow transplant (BMT). This study aims at quantifying the LCs in the oral chronic GVHD (cGVHD). METHODS: Microscopic sections from biopsies carried out in the buccal mucosa of 40 patients who underwent allogenic BMT and developed (20) or not (20) oral cGVHD (Groups 1 and 2, respectively) were utilised. For the control group, free surgical margins of 20 biopsies of non-inflammatory lesions in the buccal mucosa (Group 3) were used. The sections were studied in routine colouration and immunostained for CD1a. RESULTS: Group 1 (with cGVHD) presented a greater number of Langerhans' cells/mm(2) (50.6 +/- 37.2) when compared with the other groups (Group 2, 23.11 +/- 19.7; Group 3, 16.6 +/- 17.3). CONCLUSION: Our results suggest a greater recruitment of LCs in patients transplanted with cGVHD, probably as a result of cytokines secreted by the inflammatory cells.
