转录因子Foxp3在干燥综合征患者唇腺及外周血的表达

目的观察转录因子Foxp3在干燥综合征（SS）患者外周血及唇腺组织的表达。方法选31例SS患者（SS组）及6例健康体检者（健康对照组）,另选6份健康人和唇腺囊肿患者的唇腺标本。免疫磁珠分选受试者外周血CD4^＋T细胞,实时荧光定量PCR法检测Foxp3 mRNA表达;唇腺组织行免疫组化。观察CD4、Foxp3表达。结果（1）SS组患者唇腺组织中浸润的淋巴细胞以CD4^＋T细胞占大多数。而健康对照组唇腺组织几乎未见CD4^＋T细胞浸润。（2）两组唇腺均未见CD4^＋T细胞Foxp3^＋表达。（3）6例SS患者外周血CD4^＋T细胞Foxp3 mRNA平均相对表达水平为0．21±0．17,低于健康对照组（1．32±0．38）。差异有统计学意义（t=4．68,P〈0．0184）。SS组和健康对照组的唇腺组织均未检测到Foxp3 mRNA表达。结论转录因子Foxp3参与了SS的发病过程。     

白细胞介素-17在原发性干燥综合征患者唇腺组织和外周血的表达

目的 探讨白细胞介素(IL)-17在原发性干燥综合征(pSS)患者唇腺组织及外周血及唾液中的表达及意义.方法 采用免疫组织化学的方法对30例DSS患者及5名对照组的唇腺石蜡组织的连续切片进行IL-17、CD45RO和CD20染色.用双抗体夹心酶联免疫吸附试验(ELISA)法检测30例pSS患者和20名健康对照组外周血及唾液中IL-17水平.结果 pSS患者唇腺组织均有IL-17阳性细胞表达;而对照组无表达.在pSS患者唇腺组织少量淋巴细胞浸润组,IL-17阳性细胞数(15±5)个低于多量淋巴细胞浸润组(21±8)个(P＜0.05);但在少量淋巴细胞浸润的pSS组,IL-17阳性的淋巴细胞占总淋巴细胞的比率(14±5)%,高于多量淋巴细胞浸润组(10±4)%(P＜0.05).在大量淋巴细胞聚集的部位,IL-17主要表达在腺体外周的淋巴细胞上.呈胞质表达.相关性分析显示:IL-17阳性细胞数与红细胞沉降率(ESR)呈显著正相关(r=0.557,P＜0.05).血清中IL-17的浓度在多量淋巴细胞浸润组(7.8±0.6)pg/ml与少量淋巴细胞浸润组(7.6±1.0)pg/ml及健康对照组(7.4±1.0)pg/ml相比差异无统计学意义(P＞0.05).结论 IL-17在pSS患者中可能参与局部的炎症损伤过程.     

Parotid gland biopsy compared with labial biopsy in the diagnosis of patients with primary Sjogren's syndrome

OBJECTIVE: To assess the value of the parotid biopsy as a diagnostic tool for primary Sj?gren's syndrome (pSS), and to compare the parotid biopsy and the labial biopsy with regard to diagnostic value and biopsy-related morbidity. METHODS: In 15 consecutive patients with pSS and 20 controls, the parotid biopsy was assessed as a diagnostic tool based on the presence of lymphocytic foci, benign lymphoepithelial lesions and lymphoid follicles. These new histological criteria were compared with established diagnostic criteria for the labial biopsy in 35 consecutive patients suspected for pSS who underwent simultaneous biopsies from both sites. In addition, both biopsies were compared for morbidity. RESULTS: The first analysis revealed a focus score of >or=1 or lymphocytic infiltrates (not fulfilling the criterion of a focus score of 1) combined with benign lymphoepithelial lesions as diagnostic criteria for pSS. When comparing the parotid biopsy with the labial biopsy sensitivity and specificity were comparable (sensitivity 78%, specificity 86%). Level of pain was comparable and no loss of motor function was observed. No permanent sensory loss was observed after parotid biopsy, while labial biopsy led to permanent sensory loss in 6% of the patients. Malignant lymphoma was detected in one parotid biopsy by chance, without involvement of the labial salivary gland. CONCLUSION: A parotid biopsy has a diagnostic potential comparable with that of a labial biopsy in the diagnosis of pSS, and may be associated with less morbidity.     

Segment-specific but pathologic laminin isoform profiles in human labial salivary glands of patients with Sjogren's syndrome

OBJECTIVE: To assess the laminins in basement membrane of the labial salivary glands of patients with Sjogren's syndrome (SS) and healthy controls. METHODS: Labeling of laminin alpha1-alpha5, beta1, beta2, gamma1, and gamma2 chains was performed using immunohistochemistry with chain-specific monoclonal antibodies and pattern recognition analysis of the labeled specimens. RESULTS: Laminin alpha1, alpha2, and alpha4 chains were detected exclusively in the acinar basement membranes, whereas laminin alpha3, alpha5, beta1, gamma1, and gamma2 chains were also detected in ductal basement membranes. Laminin beta2 chain was not found. In patients with SS, laminin alpha1 and alpha2 chains were weakly labeled, but laminin alpha4 labeling was also intense in areas not infiltrated by lymphocytes. Pattern recognition analysis suggested that laminin alpha1, alpha2, and alpha4 chains were associated with acinar cells, myoepithelial cells, and tissue damage/repair, respectively. CONCLUSION: All salivary gland basement membranes signal through laminin 5, laminin 6, and laminin 10 trimers, but acinar basement membranes also signal through laminin 1, laminin 2, and laminin 8 trimers. Laminin alpha1 chain/laminin 1 may play a central role in the maintenance of acinar cells in healthy glands. This possibility was supported by the finding of variable expression of laminin alpha1 chain/laminin 1 in acinar basement membrane and its weak expression in SS with acinar cell atrophy. The impairment of myoepithelial laminin alpha2 chain/laminin 2 in patients with SS indicates a double defect in the acinar compartment and pathologic extracellular matrix-to-cell signaling, which may contribute to structural deterioration and functional abnormality of the exocrine glands.     

Changes in salivary gland immunohistology and function after rituximab monotherapy in a patient with Sjogren's syndrome and associated MALT lymphoma

OBJECTIVES: To report the successful use of rituximab on salivary gland immunohistology and function in a patient with Sjogren's syndrome (SS) and associated MALT lymphoma. CASE REPORT: The patient was a 42 year old woman with primary SS and associated MALT lymphoma located in the parotid gland and the hard palate. Four infusions of rituximab (375 mg/m(2)) weekly resulted in complete remission of the lymphoma. An incision biopsy of the parotid gland before and after treatment showed improvement of the (immuno)histopathological characteristics of SS, with possible regeneration of salivary gland tissue. Furthermore, salivary analysis showed decreased inflammatory characteristics and increased stimulated salivary flow. DISCUSSION: Rituximab is a promising agent in the treatment of SS associated MALT lymphoma. In addition to the effect on MALT lymphoma, B cell depletion by rituximab may also attenuate the activity of SS. This case report is the first to describe the effect of rituximab on histological and sialometric/chemical characteristics of SS. The efficacy of rituximab in the treatment of SS warrants further investigation.     

Management of patients presenting with Sjogren's syndrome

Sjogren's syndrome is an autoimmune exocrinopathy that predominantly affects salivary and lachrymal glands, leading to dry eyes and mouth. The most common clinical problems faced by the rheumatologist are those of dry eyes and mouth, parotid swelling, fatigue and extraglandular manifestations. The first stage in management is to make an accurate diagnosis based on the American/European consensus criteria. The most frequent differential diagnoses are dry eyes and mouth symptoms, a variant of chronic fatigue syndrome and fibromyalgia, and sialosis, which causes a non-inflammatory enlargement of the parotid glands. The mainstay of treatment for the sicca symptoms is local therapy, and that for the milder systemic symptoms is hydroxychloroquine. Steroids and immunosuppressive drugs are reserved for more severe extraglandular disease. In spite of intensive research in other systemic treatments including biologic therapies, there is limited evidence to support their use in routine clinical practice.     

Correlation between ultrasound imaging of major salivary glands and histopathological findings of labial gland biopsy samples in Sjogren's syndrome

BackgroundUltrasound imaging has been recognised as a non-invasive, reproducible method for assessing the major salivary glands. The aim of this study was to investigate the relation between ultrasound imaging of major glands and focal lymphocytic score (FS) of minor salivary glands in Sjogren's syndrome.MethodsBiopsies of labial glands and ultrasound imaging of major glands were done on 196 patients (mean age 55 years, 19 male, 177 female) attending the Sjogren's Clinic at Guy's Hospital. FS of labial glands was judged by two histopathologists whose assessment was standardised. Ultrasonography was done with a single Philips-iU22 Ultrasound machine, and a disease severity score (US) was determined. Patients were categorised into three groups: those diagnosed with Sjogren's syndrome according to the American-European classification criteria (Sjogren's syndrome group), those with non-specific sialadenitis (sialadenitis group), and those with normal biopsy results (non-salivary gland disease group).FindingsThere was a highly significant correlation between FS and US scores (mean score 1·8 [SD 2·4, range 0–11·3] vs 2·7 [2·9, 0–9], r=0·665, n=196; p<0·0001). Mean FS and US scores for the Sjogren's syndrome group were significantly greater than for the sialadenitis group (p=0·0001). For the Sjogren's syndrome group, there was a significant correlation between FS and US scores (mean score 3·6 [SD 2·6, range 0–11·3] vs 5·0 [2·4, 0–9], r=0·395, n=87; p<0·0001). For the sialadenitis group, there was a significant correlation between FS and US scores (mean score 0·4 [SD 0·6, range 0–2·3] vs 1·1 [1·7, 0–7], r=0·321, n=66; p<0·005). No obvious correlation between FS and US scores existed for the non-salivary gland disease group (mean score 0·2 [SD 0·5, range 0–2·6] vs 0·5 [SD 1·2, 0–5], n=43).InterpretationThis is the first large-scale study to show the strong relation between US scores of major salivary glands, and FS scores of minor salivary glands, suggesting a uniform disease process. Ultrasound analysis proves to be an important methodology in management and studies of Sjogren's syndrome.FundingNational Institute for Health Research.     

Correlations between salivary gland scintigraphy and histopathologic data of salivary glands in patients with primary Sjogren’s syndrome

Clinical Rheumatology - Our aim was to evaluate the association between salivary gland scintigraphy and the clinical parameters, including histological characteristics of salivary glands, in...     

Objective measures of swallowing in patients with primary Sjogren's syndrome

Primary Sjogren's syndrome (SS) is an autoimmune disorder primarily affecting salivary and lacrimal glands. Durational measures of the oral phase of swallowing were obtained on 34 patients with primary SS and 34 age-matched controls from analyses of ultrasound scans. Two conditions were examined: a basal (BA) swallow (only endogeneous secretions present in the subjects' mouths) and a 10 ml water bolus (WB) swallow. The patients with SS produced swallowing durations significantly longer (p<0.05) than those of the controls for each of the two conditions. Moreover, unlike normals, over 40% of the patients with SS produced WB swallows that were longer than their BA swallows. For further analyses, patients with SS were classified into two groups based on the difference in duration between their BA and WB swallows. These two groups differed from each other on clinical evaluations of oral motor function and presenting complaints. No significant differences were found between these two groups for salivary function or immunologic profile. These findings support the hypothesis that dysphagia can result from conditions leading to salivary gland dysfunction and document the need for the assessment of swallowing function in patients with Sjogren's syndrome.     

Heterogeneity of neutrophil antibodies in patients with primary Sjogren's syndrome

Our aims were to determine the prevalence of neutrophil antibodies in patients with primary Sjogren's syndrome (pSS), identify their target antigen(s), and evaluate their functional significance. Neutrophil antibodies were detected using an indirect immunofluorescence (IIIF) test and an enzyme-linked immunosorbent assay (ELISA), using recombinant human Fc-gamma receptor (Fc gamma RIIIb) as a capture agent. Luminol-dependent chemiluminescence was then measured by an established technique. Antibodies to neutrophils were detected in 30 of 66 patients (45%) and categorized on the basis of positivity for the two assays: IIF+/ELISA+ (group A: five patients), IIF+/ELISA- (group B: five patients), and IFF-/ELISA+ (group C: 20 patients). All positive sera contained antibodies directed to the neutrophil specific Fc gamma RIIIb, and none of them bound to NAnull neutrophils. The titer of neutrophil-reactive antibodies (groups A and B) showed no correlation with the neutrophil count, but these autoantibodies did reduce the cell ability to generate a respiratory burst. Thus, neutrophil antibodies are common in patients with pSS. Their main target appears to be Fc gamma RIII, and this may partly account for the dysfunction in Fc gamma R-mediated clearance by the reticuloendothelial system reported in these patients.