Department of Clinical Science and Biotechnology, Rheumatology Unit, University of L׳Aquila, L׳Aquila 67100, Italy.
Department of Medicine, Rheumatology Unit, University of Perugia, Perugia, Italy.
Semin Arthritis Rheum. 2014 Dec;44(3):314-24. doi: 10.1016/j.semarthrit.2014.05.015. Epub 2014 May 15.
Several histological scoring systems, including the focus score, performed in minor salivary glands (MSGs) by hematoxylin-eosin (H&E) staining, have been employed in clinical practice to assess the inflammatory infiltrate and provide the diagnosis of primary Sjo¨gren׳s syndrome (pSS). Aims of this study were to integrate different scoring systems and identify potential differences in the molecular profile of lymphoid cytokines related to germinal center (GC) formation and clinical subsets in pSS.
Overall, 104 pSS patients and 40 subjects with sicca non-pSS were retrospectively evaluated. MSG biopsies were evaluated by H&E and immunofluorescence to assess histological pattern, Chisholm and Mason grading system, Tarpley score, a grading for the severity of inflammatory infiltrate, T-/B-cell segregation, and the presence of GC. MSGs from 50 pSS patients and 30 sicca non-pSS patients were processed by real-time PCR to assess LTα, LTβ, BAFF, CXCR4, CXCL12, CXCR5, CXCL13, CCR7, CCL19, and CCL21.
GCs presence was associated with anti-Ro/SSA and anti-La/SSB antibodies, hypergammaglobulinemia, salivary gland swelling, higher Tarpley score and focus score, and extraglandular involvement but, at multivariate analysis, only extraglandular involvement was independently associated to GC. pSS patients displayed higher level of all cytokines compared to those with sicca symptoms. GC(+) pSS patients displayed higher level of all cytokines compared to those GC(-).
Our study demonstrates that different histopathological patterns, including GC presence, reflect different cytokine expression and different clinical subsets. We believe that the combined immunofluorescence/molecular approach in MSGs would help to tailor diagnostic and therapeutic approach for different subsets of pSS patients.
几种组织学评分系统,包括苏木精-伊红(H&E)染色的小唾液腺(MSG)焦点评分,已在临床实践中用于评估炎症浸润并提供原发性干燥综合征(pSS)的诊断。本研究的目的是整合不同的评分系统,并确定与生发中心(GC)形成和 pSS 临床亚型相关的淋巴细胞因子的分子谱中的潜在差异。
回顾性评估了 104 例 pSS 患者和 40 例干燥非 pSS 患者。通过 H&E 和免疫荧光评估 MSG 活检以评估组织学模式、Chisholm 和 Mason 分级系统、Tarpley 评分、炎症浸润严重程度的分级、T-/B 细胞分离和 GC 的存在。对 50 例 pSS 患者和 30 例干燥非 pSS 患者的 MSG 进行实时 PCR 处理,以评估 LTα、LTβ、BAFF、CXCR4、CXCL12、CXCR5、CXCL13、CCR7、CCL19 和 CCL21。
GC 的存在与抗 Ro/SSA 和抗 La/SSB 抗体、高丙种球蛋白血症、唾液腺肿胀、更高的 Tarpley 评分和焦点评分以及腺外受累相关,但在多变量分析中,只有腺外受累与 GC 独立相关。与有干燥症状的患者相比,pSS 患者显示出更高水平的所有细胞因子。与 GC(-)pSS 患者相比,GC(+)pSS 患者显示出更高水平的所有细胞因子。
我们的研究表明,不同的组织病理学模式,包括 GC 的存在,反映了不同的细胞因子表达和不同的临床亚型。我们相信,MSG 中的联合免疫荧光/分子方法将有助于针对不同的 pSS 患者亚组定制诊断和治疗方法。