Frequência de centros germinativos e caracterização de células dendríticas mieloides e plasmocitoides na síndrome de Sjögren
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Data
2021-03-05
Autores
Silva, Evânio Vilela da
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Universidade Estadual Paulista (Unesp)
Resumo
A síndrome de Sjögren (SS) é uma doença autoimune crônica sistêmica que afeta principalmente as glândulas salivares e lacrimais, ocasionando xerostomia e ceratoconjuntivite sicca, respectivamente. A histopatologia de biópsias de glândulas salivares menores (GSm) exibindo sialadenite linfocítica focal (SLF) com um escore focal ≥1, é um critério diagnóstico importante para definir o dignóstico de SS. Em alguns casos, a SLF mostra a presença de centros germinativos (CGs). Alguns estudos sugerem que CGs na SLF pode ser preditivo para o desenvolvimento de linfoma em pacientes com SS. As células dendríticas (CDs) são eficientes células apresentadoras de antígenos e foram sugeridas agir modulando a ativação de células T e B na SS; no entanto, a sua contribuição precisa ser melhor esclarecida. Este estudo analisou a frequência de CGs e a presença de CDs mieloides e plasmocitoides em biópsias de GSm de pacientes com SS primária (SSp). Cinquenta casos de SSp (grupo SSp) e 31 casos de lesões orais reativas (não SS, não sicca, grupo controle) contendo também características típicas de SLF, foram avaliados por análise morfológica e imunoistoquímica (CD10, CD23 e Bcl-6), visando à detecção de CGs. Além desses, para caracterizar a presença de CDs, foram utilizados os seguintes anticorpos CD1a, CD207, CD123 e CD303. A análise morfológica revelou CGs em 20% (10/50) e 19% (6/31) do grupo SSp e controle, respectivamente. O número de focos foram significativamente maiores no grupo SSp do que no grupo controle com FS <1. A imunoistoquímica confirmou todos os achados morfológicos (CG mostrando positividade para CD23 e Bcl-6, com expressão variável de CD10) e adicionalmente em 3 e 1 casos do grupo SSp e controle, respectivamente. A análise imunoistoquímica para CDs, no grupo SSp, revelou uma população heterogênea de células de Langerhans (CLs) CD1a+ e CD207+ localizadas preferencialmente em padrão periductal, e de CDs plasmocitoides (CDp) CD123+ e CD303+ distribuídas na periferia dos infiltrados inflamatórios; enquanto que, no grupo controle, essas células foram escassas (CLs, p<0,05). Em conclusão, este trabalho mostra que a SLF também pode ser observada quando examinando lesões orais reativas, as quais apresentaram frequência de CGs semelhante às encontradas em pacientes com SSp. Ainda, a imunoexpressão de marcadores de CDs em pacientes com SSp sugere a participação dessas células na perpetuação do processo imunoinflamatório na SSp, contribuindo na elucidação de alvos imunoterapêuticos.
Sjögren's syndrome (SS) is a chronic autoimmune disease that mainly affects the salivary and lacrimal glands, causing xerostomia and ceratoconjunctivitis sicca, respectively. Histopathology of minor salivary glands (mGSs) biopsies showing the presence of focal lymphocytic sialadenitis (FLS) with focal score ≥1 is an important diagnostic criterion to define SS. In some cases, the FLS shows the presence of germinal centers (GCs).Some studies suggest that GCs in FLS may be predictive for lymphoma development in SS patients. Dendritic cells (CDs) are efficient antigen presenting cells and have been suggested to act by modulating the activation of T- and B-cells in SS, however, their contribution needs to be further clarified. This study analyzed the frequency of GC and the presence of myeloid and plasmacytoid DCs in mGSs biopsies of patients with primary SS (pSS).Fifty cases of primary SS (pSS group) and 31 cases of oral reactive lesions (non-SS non-sicca, control group) containing also typical FLS features, were assessed by morphological and immunohistochemical (CD10, CD23 and Bcl-6) analysis, aiming at the detection of GCs. In addition to these, to characterize the presence of DCs, the following antibodies CD1a, CD207, CD123 and CD303 were used. The morphological analysis revealed CGs in 20% (10/50) and 19% (6/31) of the pSS and control group, respectively. The FS and number of foci were significantly higher in pSS than control group with FS<1. Immunohistochemistry confirmed all morphological findings (GCs showing CD23 and Bcl-6 positivity, with variable CD10 expression) and additionally in 3 and 1 cases of the pSS and control group, respectively. Moreover, another 6 and 2 cases of the pSS and control group with FS≥1, respectively, showed positivity only for CD23. Immunohistochemical analysis for DCs, in the pSS group, revealed a heterogeneous population of CD1a+ and CD207+ Langerhans cells, preferably located in a periductal pattern, and of CD123+ and CD303+ plasmacytoid DCs (pDCs) distributed on the periphery of inflammatory infiltrates; whereas, in the control group, these cells are scarce (LCs, p<0,05). In conclusion, this study demonstrated that FLS can also be observed when assessing of reactive oral lesions, which showed similar frequency of GCs with those found in SSp patients. In addition, the immunoexpression of DCs in pSS patients suggest the participation of these cells in the perpetuation of the inflammatory process in pSS, contributing to the elucidation of immunotherapeutic targets.
Sjögren's syndrome (SS) is a chronic autoimmune disease that mainly affects the salivary and lacrimal glands, causing xerostomia and ceratoconjunctivitis sicca, respectively. Histopathology of minor salivary glands (mGSs) biopsies showing the presence of focal lymphocytic sialadenitis (FLS) with focal score ≥1 is an important diagnostic criterion to define SS. In some cases, the FLS shows the presence of germinal centers (GCs).Some studies suggest that GCs in FLS may be predictive for lymphoma development in SS patients. Dendritic cells (CDs) are efficient antigen presenting cells and have been suggested to act by modulating the activation of T- and B-cells in SS, however, their contribution needs to be further clarified. This study analyzed the frequency of GC and the presence of myeloid and plasmacytoid DCs in mGSs biopsies of patients with primary SS (pSS).Fifty cases of primary SS (pSS group) and 31 cases of oral reactive lesions (non-SS non-sicca, control group) containing also typical FLS features, were assessed by morphological and immunohistochemical (CD10, CD23 and Bcl-6) analysis, aiming at the detection of GCs. In addition to these, to characterize the presence of DCs, the following antibodies CD1a, CD207, CD123 and CD303 were used. The morphological analysis revealed CGs in 20% (10/50) and 19% (6/31) of the pSS and control group, respectively. The FS and number of foci were significantly higher in pSS than control group with FS<1. Immunohistochemistry confirmed all morphological findings (GCs showing CD23 and Bcl-6 positivity, with variable CD10 expression) and additionally in 3 and 1 cases of the pSS and control group, respectively. Moreover, another 6 and 2 cases of the pSS and control group with FS≥1, respectively, showed positivity only for CD23. Immunohistochemical analysis for DCs, in the pSS group, revealed a heterogeneous population of CD1a+ and CD207+ Langerhans cells, preferably located in a periductal pattern, and of CD123+ and CD303+ plasmacytoid DCs (pDCs) distributed on the periphery of inflammatory infiltrates; whereas, in the control group, these cells are scarce (LCs, p<0,05). In conclusion, this study demonstrated that FLS can also be observed when assessing of reactive oral lesions, which showed similar frequency of GCs with those found in SSp patients. In addition, the immunoexpression of DCs in pSS patients suggest the participation of these cells in the perpetuation of the inflammatory process in pSS, contributing to the elucidation of immunotherapeutic targets.
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Palavras-chave
Síndrome de Sjogren, Glândulas salivares menores, Centro germinativo, Células dendríticas, Imuno-histoquímica, Sjogren’s syndrome, Salivary glands minor, Germinal center, Dendritic cells, Immunohistochemistry