原发性干燥综合征患者血清B淋巴细胞刺激因子水平的检测

目的检测原发性干燥综合征(pSS)患者血清中B淋巴细胞刺激因子(BLys)的水平,探讨其在pSS发病机制中的作用。方法pSS患者50例,采用酶联免疫吸附试验(ELISA)检测血清BLyS水平,速率散射比浊法检测类风湿因子(RF)、免疫球蛋白IgG、IgM、IgA及补体C3、C4水平,间接免疫荧光法及免疫印迹法检测抗核抗体(ANA)、抗SSA抗体、抗SSB抗体的水平。对照组30名为我院门诊的健康体检者,性别、年龄构成与pSS患者组匹配。分析BLyS在pSS患者血清中的水平及其与RF、免疫球蛋白、补体、ANA、抗SSA抗体、抗SSB抗体的相关性。结果血清BLyS平均水平在pSS患者组为(560±380)pg/ml,在对照组为(195±93)pg/ml,pSS患者组明显高于对照组(P＜0．01),血清BLyS水平与RF、IgG、丙种球蛋白呈正相关(r=0．598,P＜0．01；r=0．522,P＜0．01；r=0．547,P＜0．01),与IgA、IgM、C3、C4无明显相关性。ANA和抗SSA抗体、抗SSB抗体阳性者血清BLyS水平高于上述指标正常者。结论pSS患者的血清BLyS水平升高,且与免疫球蛋白定量、自身抗体表达有相关性。BLys的异常表达可能是pSS发病的重要环节。     

抗SSA和SSB抗体均阳性的原发性干燥综合征患者的临床资料分析

原发性干燥综合征(pSS)是一种以侵犯泪腺、唾液腺等外分泌腺体,具有高度淋巴细胞浸润为特征的弥漫性结缔组织病[1].pSS患者血清中可出现抗核抗体(ANA)、抗SSA抗体、抗SSB抗体和抗着丝点抗体(ACA)等多种自身抗体.国内外文献多报道抗SSA抗体(或)抗SSB抗体阳性pSS患者的临床特点[2-4].本研究分析了抗SSA抗体、抗SSB抗体均阳性的pSS患者的临床资料,旨在了解其临床特点.     

慢性丙型肝炎病毒感染相关性干燥症与原发性干燥综合征临床对比分析

目的研究分析慢性丙型肝炎病毒感染相关性干燥症(SSAHCVI)与原发性干燥综合征(pSS)在临床方面的异同。方法对27例SSAHCVI和56例pSS患者详细记录有无口眼干燥等临床表现,实验室进行血、尿常规、血沉、C反应蛋白,肝、肾功能,有关免疫学项目及其他检查。结果SSAHCVI组和pSS组比较有相似的临床表现,如口眼干燥、关节痛、关节炎、皮肤血管炎、肝脏损害等。不同点SSAHCVI组年龄偏大(60±7)岁vs(56±8)岁,P<0.05;病程短(5.7±2.4)年vs(8.4±1.2)年,P<0.01;男性多见(性别3.5∶1vs1∶7);口干症状明显,P=0.0568;皮肤血管炎如雷诺征,紫癜阳性发生率高;肾小管酸中毒,肺间质病变,萎缩性胃炎,腮腺肿大发生率低;ALT、AST、TBIL、DBIL升高发生率高,P<0.01~0.05;ANA、抗SSA/SSB抗体,阳性率低;补体C3、C4下降,冷球蛋白(CG)升高发生率高,P<0.01。结论SSAHCVI患者有别于pSS患者的特点,主要是口干症状明显,肝脏常受累,多伴冷球蛋白血症,肺、肾、胃受累较少,缺乏抗SSA/SSB抗体。     

初诊原发性干燥综合征86例临床研究

目的 探讨初诊原发性干燥综合征(pSS)的临床特点,旨在提高对pSS的早期诊断水平.方法 对2006～2007本院86例旨次诊断为pSS的住院患者临床表现及实验室指标进行回顾总结.结果 除口干、眼干、关节痛外,患者血液系统受累较为多见.18岁以下青少年患者口干、眼干发生率低,而出现发热、淋巴结肿大比例高.抗SSA或SSB抗体阳性患者血液系统损害发生率高,并且红细胞沉降率(ESR)增快、球蛋白或免疫球蛋白G增高、抗核抗体(ANA)及类风湿因子(RF)阳性较抗SSA或SSB抗体阴性患者更多见.结论 干燥综合征(SS)并不是都呈良性疾病过程,部分患者早期即存在重要脏器损伤.年轻患者出现不明原因发热、球蛋白增高、RF阳性者应注意排除SS可能.     

原发性干燥综合征相关间质性肺疾病患者血清活性氧、转录因子κB及转化生长因子β_1水平变化及其临床意义研究

目的观察原发性干燥综合征相关间质性肺疾病(pSS-ILD)患者血清活性氧(ROS)、转录因子κB(NF-κB)及转化生长因子β_1(TGF-β_1)水平变化,并探讨其临床意义。方法选取2015年7月—2017年6月宁夏回族自治区人民医院呼吸科和风湿科收治的女性原发性干燥综合征(pSS)患者94例,其中单纯pSS患者46例作为pSS组,pSS-ILD患者48例作为pSS-ILD组;另选取同期体检健康女性50例作为对照组。采用免疫印迹法检测抗干燥综合征A(SSA)抗体、抗干燥综合征B(SSB)抗体、抗Robert52(Ro52)抗体,采用酶联免疫吸附试验(ELISA)检测血清ROS、NF-κB及TGF-β_1水平;血清NF-κB水平与pSS-ILD患者血清ROS及TGF-β_1水平的相关性分析采用Pearson相关性分析。结果 pSS组和pSS-ILD组患者抗SSA抗体、抗SSB抗体及抗Ro52抗体阳性率高于对照组(P<0.05);pSS组和pSS-ILD组患者抗SSA抗体、抗SSB抗体及抗Ro52抗体阳性率比较,差异无统计学意义(P>0.05)。pSS组和pSS-ILD组患者血清ROS、NF-κB及TGF-β_1水平高于对照组,pSS-ILD组患者血清ROS、NF-κB及TGF-β_1水平高于pSS组(P<0.05)。Pearson相关性分析结果显示,血清NF-κB水平与pSS-ILD患者血清ROS(r=0.95)及TGF-β_1(r=0.98)水平呈正相关(P<0.05)。结论 pSS-ILD患者血清ROS、NF-κB及TGF-β_1水平明显升高,且血清NF-κB水平与血清ROS、TGF-β_1水平有关,推测ROS-NF-κB-TGF-β_1信号通路可能与pSS-ILD的发生有关。     

原发性干燥综合征患者外周血B细胞FcγRⅡb的表达及临床意义

目的 探讨原发性干燥综合征(pSS)患者外周血B细胞FcγRⅡb的表达及其临床意义.方法 流式细胞术检测19例pSS患者、15名健康对照外周血B细胞FcγRⅡb的平均荧光强度(MFI);酶联免疫吸附试验( ELISA)方法测定19例pSS患者血清抗SSA、SSB抗体水平,统计学分析采用t检验、单因素方差分析、SNK-q检验及Pearson相关分析.结果 pSS患者CD 19+CD27+记忆性B细胞亚群的百分率[(20.8±2.7)％,19例]显著低于健康对照组[(37.8±2.2)％,15名](t=-4.002,P＜0.01);活动期pSS患者外周血CD19+CD27+记忆性B细胞FcγRⅡb的MFI[( 74±8),13例]低于非活动期组[(132±11),6例]及健康对照组[(139±12),15名](F=10.699,P＜0.01);pSS患者外周血CD19+CD27+记忆性B细胞FcγRⅡb的MFI与pSS疾病活动指数(SSDAI)呈负相关(r=-0.744,P=0.0003);抗SSA、SSB抗体阳性组pSS患者CD19+CD27+记忆性B细胞FcγRⅡb的MFI[分别为(75±3),12例;(48±7),5例]显著低于抗SSA、SSB抗体阴性组[分别为(122±11),7例;(108±9),14例](t分别为-4.336和-3.776,P均＜0.01);抗SSA抗体阳性组pSS患者CD19+CD27+记忆性B细胞FcγRⅡb的MFI与抗SSA抗体滴度呈负相关(r=-0.685,P=0.014).结论 pSS患者活动期外周血记忆性B细胞FcyRⅡb表达与SSDAI呈负相关,并与抗SSA抗体呈负相关.FcγR Ⅱb表达异常可能在pSS免疫发病机制中起重要作用.     

原发性和继发性干燥综合征肺间质病变的临床分析

目的了解原发性和继发性干燥综合征(SS)肺间质病变的发生情况、临床特点、肺功能、影像学检查及相关因素,以早期发现SS的肺部病变。方法回顾性分析我院2002年1月至2005年7月资料完整的原发性和继发性SS患者136例的临床资料,包括抗SSA抗体和抗SSB抗体,胸部X线、肺高分辨CT(HRCT)、肺功能等。结果①抗SSA抗体阳性的原发性SS(pSS)患者易出现肺间质病变,而且病变较重;②肺HRCT示继发性SS(sSS)肺间质病变程度比pSS肺间质病变程度重,可能受其病程长的影响;③pSS肺间质病变者其肺容量减少、顺应性降低较sSS肺间质病变者更多见,sSS肺间质病变者以阻塞性通气障碍为主,二者肺功能损害均以小气道及弥散功能损害为主。结论SS患者应早期做肺HRCT及肺功能检查,以早期诊断和治疗肺间质病变,尤其是抗SSA抗体阳性pSS患者。     

以肾损害为首要表现的抗SSA/SSB抗体阴性的原发性干燥综合征1例报告

<正>原发性干燥综合征（primary Sj?gren’s syndrome,pSS）以口眼干燥为主要临床表现,抗SSA/SSB抗体是本病的标志性抗体,多个pSS国际分类标准将抗SSA抗体/抗SSB抗体阳性作为诊断条件之一。然而,当患者抗SSA/SSB抗体阴性,口眼干燥的症状轻微,并同时以突出的肾脏损害为首要表现时,诊断较为困难。现报道1例以肾损害为首要表现的抗SSA/SSB抗体阴性的pSS病例,以期进一步提高临床医生对该病的认识,避免漏诊或误诊。     

抗α-胞衬蛋白多肽IgA抗体对干燥综合征的诊断价值

目的以α-胞衬蛋白(α-Fodrin)多肽为抗原,采用ELISA检测干燥综合征(Sjgren's syndrome,SS)患者血清抗α-Fodrin多肽IgA抗体(α-Fodrin-derived polypeptide antibody,αF5-IgA),并分析其与SS临床表现和其他实验室指标的关系。方法以固相法合成的α-Fodrin 37-59多肽(αF5)为包被抗原,ELISA定量检测169例原发性干燥综合征(primary Sjgren's syndrome,pSS)、31例继发性干燥综合征(secondary Sjgren syndrome,sSS)、221例其他结缔组织病患者及88名健康对照者血清抗α-Fodrin37-59多肽IgA(αF5-IgA)抗体水平,并分析其与SS患者临床表现及自身抗体、IgG、IgA、血沉及血常规等的相关性。结果 ELISA定量检测抗αF5-IgA抗体,pSS和sSS组的阳性率分别为73.4%和64.5%,而类风湿关节炎、系统性红斑狼疮和健康对照组的阳性率分别是27.3%、17.8%和2.3%,抗αF5-IgA抗体在SS患者的阳性率显著高于其他结缔组织病患者及健康对照组(χ2=114.5～234.1,P0.01)。抗αF5-IgA抗体对SS诊断的特异性为86.1%,在抗SSA、抗SSB抗体和ANA阴性的pSS患者中,抗αF5-IgA抗体的阳性率分别为48.9%、46.6%和57.1%。抗αF5-IgA抗体阳性pSS患者的肾脏受累率高于抗αF5-IgA抗体阴性患者(χ2=3.0,P0.05)。抗αF5-IgA抗体阳性pSS患者IgG、IgA升高,血沉增快,白细胞与血小板下降的概率明显高于抗体阴性的患者(χ2=17.9～73.5,P0.05)。结论 ELISA法可用于检测SS患者血清抗αF5-IgA抗体,该抗体为诊断SS较为特异的自身抗体之一,且抗αF5-IgA抗体对其他自身抗体阴性的SS的诊断有参考意义。     

抗α-胞衬蛋白抗体在干燥综合征诊断及病情判断中的作用

目的探讨抗α-胞衬蛋白（Fodrin）抗体在干燥综合征（SS）诊断及病情判断中的作用。方法应用酶联免疫吸附试验（ELISA）检测40例原发性SS（pSS）、24例继发性SS（sSS）、32例其他结缔组织病（CTD）和31例非CTD患者血清抗α-Fodrin—IgA、IgG抗体,同时记录SS患者的临床资料。结果抗α-Fodrin-IgA、IgG抗体诊断ss的敏感性分别为31．3％、28．1％,特异性分别为90．5％、88．9％;同时检测两型抗体诊断ss的敏感性显著提高,达48．4％（P〈0．05）。pSS和sSS患者抗α-Fodrin抗体（I型或Ⅱ型）的阳性率均显著高于非CTD组（P〈0．05）;SS患者抗α-Fodrin抗体的出现与临床症状、眼部体征及核素检查显示的唾液腺功能受损无明显相关性（P〉0．05）;抗α-Fodrin抗体阳性患者血清C反应蛋白高于阴性者（P〈0．05）;抗核抗体（ANA）、抗SSA（干燥综合征抗原A）、抗SSB（干燥综合征抗原B）抗体3项阴性的患者抗α-Fodrin抗体阳性率为36．4％。结论抗α-Fodrin抗体特异性较好,对诊断SS有一定参考价值,尤其对于ANA、抗SSA、抗SSB抗体阴性的患者,且可能有助于评估SS病情活动性。     

原发性胆汁性胆管炎合并甲状腺疾病患者临床特征分析

目的:探究原发性胆汁性胆管炎(PBC)合并甲状腺疾病(TD)患者的临床特征,以及两者之间的联系。方法:回顾性分析青岛大学附属医院2005—2017年确诊为PBC的患者,根据是否合并TD将患者分组,对2组患者的一般情况和临床特征进行组间比较。采用独立样本t检验、非参数检验、χ^2检验或Fisher确切概率法进行分析。结果:资料完整的148例PBC患者中45例(30.4%)合并TD。合并TD的PBC患者出现SS的比例更高(33.3%比17.5%,χ^2=4.545,P=0.033),其血清抗SP100抗体和抗SSB抗体的阳性率较未合并TD患者高,2组间差异有统计学意义(20.0%比5.8%,χ^2=5.440,P=0.020;20.0%比2.9%,χ^2=10.087,P=0.001)。未合并TD的PBC患者腹胀和黄疸发生率较高(29.1%比11.1%,χ^2=5.629,P=0.018;23.3%比8.9%,χ^2=4.241,P=0.039),总胆红素(TBIL)、直接胆红素(DBil)和ALP更易高于正常值,2组间差异有统计学意义(40.8%比17.8%,χ^2=7.405,P=0.007;43.7%比17.8%,χ^2=9.147,P=0.002;69.9%比51.1%,χ^2=4.811,P=0.028),肝纤维化和门静脉高压常见,2组间差异有统计学意义(40.8%比22.2%,χ^2=4.731,P=0.030;25.2%比8.9%,χ^2=5.183,P=0.023)。结论:TD不影响PBC的自然病程。PBC合并TD患者较少出现肝纤维化、门脉高压和胆汁淤积,但易合并SS,应加强多科室的联合诊断和治疗。     

In primary Sjögren's syndrome,HLA class II is associated exclusively with autoantibody production and spreading of the autoimmune response

OBJECTIVE: To reevaluate, in a large series of patients with Sj?gren's syndrome (SS) recruited from 2 French centers, the question of whether HLA is associated with SS itself or with a pattern of secretion of autoantibodies. METHODS: One hundred forty-nine white patients fulfilling the American-European Consensus Group criteria for SS were divided into 3 subgroups, according to their anti-Ro/SSA and anti-La/SSB status, as follows: group 1 (n = 53), no antibody; group 2 (n = 46), anti-SSA only; group 3 (n = 50), both anti-SSA and anti-SSB. Patients were compared with 222 unrelated healthy subjects representative of the white population in France. RESULTS: Comparisons between the 149 SS patients and 222 controls confirmed the association of SS with DRB1*03 (the frequency was 25% in patients versus 10% in controls) and DQB1*02 (32% versus 22%). The association between HLA and SS was restricted to patients with anti-SSA and/or anti-SSB; no association with HLA was observed in patients in group 1 (no antibody). The frequency of HLA-DRB1*15 was highest in group 2 (24%), compared with 11% in group 1 and 11% in controls, whereas the frequency of HLA-DRB1*03 was highest in group 3 (44%), compared with 12% in group 1, 19% in group 2, and 10% in controls. Group 2 and group 3 had more clinical and biologic markers of activity than did group 1 but were not clinically different. HLA alleles were not associated with clinical features of the disease, and were associated with only some biologic features: rheumatoid factor positivity, increased serum IgG, and thrombocytopenia were associated with HLA-DRB1*03, and neutropenia was associated with DQB1*01. CONCLUSION: HLA class II markers confer genetic susceptibility to Sj?gren's syndrome. The association between HLA and SS is restricted to patients with anti-SSA and/or anti-SSB antibodies; HLA is not associated with SS in patients without these autoantibodies. The absence of a difference in disease severity between groups 2 and 3, as well as the restricted association of HLA-DRB1*03 in group 3, strongly suggest that HLA alleles predispose to autoantibody secretion, without being associated with clinical outcome. HLA class II phenotype might support epitope spreading: HLA-DR15 favors anti-SSA synthesis, whereas HLA-DR3 is associated with both anti-SSA and anti-SSB production.     

Mucosal microvilli in dry eye patients with chronic GVHD

The ocular surface is a frequent target tissue of mucosal chronic GVHD (cGVHD). We investigated the histopathological features of the conjunctival microvilli in patients with cGVHD. Conjunctival tissue specimens from patients with cGVHD or Sj?gren's syndrome (SS) or from healthy individuals were examined by light microscopy and EM, impression cytology, and immunohistochemistry. The cGVHD conjunctivae showed significantly more metaplasia and fewer goblet cells than the SS and normal conjunctivae. Abundant CD8(+) T cells infiltrated the basal epithelia in the cGVHD conjunctiva. The microvilli per standard epithelial unit and the secretory vesicles were counted by analyzing electron micrographs. The mean number of mucosal microvilli was significantly lower in the cGVHD than that in the SS or normal specimens, and the microvilli were significantly shorter, with a smaller height-width ratio. The mean number of secretory vesicles was also significantly lower, and the membrane-spanning mucin thinner, in the cGVHD compared with the SS and normal specimens. Thus, the conjunctival mucosal microvilli of cGVHD patients were significantly different in number and morphology from those of SS and normal subjects. These may be important factors affecting the stability of the tear-film layer and its contribution to cGVHD-related dry eye.     

Adult heart block is associated with disease activity in primary Sjögren's syndrome

OBJECTIVES: Congenital heart block occurring in the foetus and neonate may be associated with maternal anti-SS-A/anti-SS-B autoantibodies (anti-SSA/anti-SSB). The adult atrioventricular node is generally thought to be resistant to the damaging effects of anti-SSA/anti-SSB. However, case reports suggest that heart block developing in adult Sj?gren's syndrome (SS) patients may be associated with these autoantibodies. Therefore, we investigated the relationship between serum antibodies and heart block in adult SS patients. METHODS: We abstracted data from clinic patient records. Diagnosis of primary SS was based on American-European classification criteria. Electrocardiograms (EKGs), laboratory immunology parameters, lipid profiles, and focus scores from labial salivary gland biopsies were available for 51 SS patients. Fifteen patients had follow-up EKGs. PR interval200 ms was considered to be first-degree heart block. RESULTS: Five patients showed prolonged PR intervals; the presence of heart block was not related to the presence of anti-SSA antibodies. However, significant differences between patients with prolonged and normal PR intervals were seen for mean focus scores (p<0.0001), anti-cardiolipin immunoglobulin IgG (p = 0.0009), age (p = 0.01), IgG (p = 0.02), anti-SSB antibodies (p = 0.02), and high density lipoprotein (HDL) cholesterol levels (p = 0.03). These parameters correlated with prolonged PR intervals. CONCLUSIONS: These results suggest an association between disease activity, the presence of anti-SSB antibodies, and the occurrence of first-degree heart block in adults with primary SS.     

Association of transforming growth factor beta1 and tumor necrosis factor alpha polymorphisms with anti-SSB/La antibody secretion in patients with primary Sjögren's syndrome

OBJECTIVE: To determine whether cytokine gene polymorphisms of interferon-gamma (IFNgamma), interleukin-6 (IL-6), IL-10, tumor necrosis factor alpha (TNFalpha), and transforming growth factor beta1 (TGFbeta1) predispose subjects to the development of primary Sj?gren's syndrome (SS). METHODS: Single-base-exchange cytokine gene polymorphisms were analyzed in 129 French patients with primary SS who fulfilled the American-European Consensus Group criteria, as well as in 96 unrelated healthy subjects. RESULTS: The frequency of the TNF-308A (TNF2) allele was significantly higher in the SS patients (26% versus 11%). This TNF2 association was restricted to patients with anti-SSB (37% versus 11% in controls). Stratification did not reveal an independent effect of TNF2 and HLA-DRB1*03 on disease or on anti-SSB antibody secretion. The frequency of allele C at codon 10 of TGFbeta1 was strongly increased in the subgroup of patients with anti-SSB; this allele acted synergistically with DRB1*03 to predispose patients to the secretion of anti-SSB. The IL-10 GCC haplotype carrier rate was significantly higher in SS patients than in controls (67% versus 48%), but the IL-10 allele and genotype frequencies were not significantly different. No association was found between IL-6 or IFNgamma polymorphisms and primary SS. CONCLUSION: TNF2 was associated with anti-SSB antibody secretion, although this association was not independent of the association with DRB1*03. Allele C at codon 10 of TGFbeta1 was found to act synergistically with DRB1*03 in predisposing patients to the secretion of anti-SSB. These results therefore suggest that most of the known genetic predisposition to primary SS might concern the pattern of autoantibody diversification.     

Seroprevalence of Helicobacter pylori in primary Sj?gren's syndrome.

OBJECTIVE: To study the seroprevalence of Helicobacter pylori (H. pylori) infection in patients with primary Sj?gren's syndrome (SS), fulfilling the 1993 European classification criteria compared with three different control groups. METHODS: Serological tests investigating the presence of antibodies against H. pylori were performed by Enzyme Immuno Assay (EIA) and confirmed by immunoblot (IB). The samples were tested for antibodies against cytotoxin-associated-protein A (CagA). The three control groups included were: one simultaneously collected age-matched group of orthopaedic outpatients without rheumatological disease, a random primary care patient sample from the same geographic region and a group of age-matched blood donors. RESULTS: 45% of the SS patients (n = 164) were EIA-positive for H. pylori and 30% were positive in the confirming IB assay. 23% had antibodies to the CagA protein. We found a clear and statistically significant increase in seroprevalence with increasing age. These estimates were lower compared to the control group of orthopaedic patients but similar to those in the other two control groups, thus showing the importance of multiple control groups in case control studies. In the group of SS patients there were no significant associations between a positive EIA, IB or CagA for H. pylori and the presence of abnormal serum levels of autoantibodies (ANA, anti-SSA, anti-SSB, rheumatoid factor (RF)) or an abnormal lip biopsy. CONCLUSION: Swedish patients with primary SS do not have higher H. pylori seroprevalence rates than controls. Neither was H. pylori seropositivity associated with the presence of immunological markers of SS such as circulating autoantibodies or a lip biopsy with abnormal focus score.     

Autoantibodies and rheumatic disorders in a neurology inpatient population: a prospective study

PURPOSE: To determine the prevalence and spectrum of underlying rheumatic diseases, especially Sj?gren's syndrome (SS) and the antiphospholipid syndrome, and the prevalence of the lupus anticoagulant, antinuclear antibody (ANA), and rheumatoid factor (RF) within a neurologic patient population. PATIENTS AND METHODS: The study design entailed a prospective, consecutive sample of patients admitted to a university-affiliated neurology service for 72 hours or more. Study patients were obtained from a sequential evaluation of 100 inpatients with a wide spectrum of neurologic diseases. Another 31 eligible patients were not included due to refusal (n = 4), inability to give consent (n = 12), or an incomplete database (n = 15). All patients underwent a physical examination and responded to a rheumatic disease questionnaire (administered by one rheumatologist) assessing signs and symptoms relevant to rheumatic disease. All had lupus anticoagulant, ANA, and RF determinations. An independent patient evaluation was done by the attending neurologist. RESULTS: Eleven patients had a rheumatic or autoimmune disorder directly related to their neurologic admission: three patients with SS (one each with embolic stroke, dementia, and hemiparetic somatization); three patients with lupus anticoagulant syndrome (all with stroke, recurrent in two); one patient with systemic lupus erythematosus accompanied by migraine headache and the lupus anticoagulant; and one patient each with isolated central nervous system (CNS) angiitis, neuro-Beh?et's disease, CNS Whipple's disease, and HLA-B27-associated spondyloarthropathy. Nineteen patients had one or more autoantibodies: ANA greater than or equal to 1:80 (n = 10); RF greater than or equal to 1:80 (n = 6); and positive lupus anticoagulant (n = 7). The seroreactivity of 10 of these patients remained unexplained. CONCLUSIONS: This neurologic population demonstrated significant seroreactivity and rheumatic disease associations, with SS and lupus anticoagulant-related neurologic disease the most common. Since SS and the antiphospholipid syndrome can be overlooked, it is recommended that a formal evaluation for SS and a direct lupus anticoagulant assay should be considered in the examination of patients with neuropsychiatric symptoms.     

Pathogenesis of Sj?gren's syndrome.

Sj?gren's syndrome is a systemic autoimmune disease characterized by lymphocytic infiltrations of lacrimal and salivary glands. SS patients produce a variety of autoantibodies, including RF and ANA. Genetic factors, including HLA-DR3, predispose to primary SS. In contrast to normal SGs, the SS SG epithelial cells express high levels of HLA-DR antigens. This class II gene expression on the target organ may represent the structural basis for HLA-associated disease susceptibility. The glands are infiltrated with CD4+ T cells that can produce cytokines, including IL-2 and interferon-gamma. B cells within the SG produce autoantibodies, including RF. These SG B cells frequently use the VKIIIb subgroup of kappa light chain, a feature that SS patients share with Waldenstrom's macroglobulinemia patients. B cells undergo small clonal expansions that can be detected on Southern blot as immunoglobulin gene rearrangements, and SS patients have a markedly increased risk of developing non-Hodgkin's B-cell lymphoma involving the SGs and cervical lymph nodes. Due to accessibility of the SG for biopsy and the characteristic patterns of autoantibody production, SS provides an opportunity to study the target organ for autoimmune destruction and the transition from autoimmunity to lymphoma.     

Anti-SSB/La antibodies in Sj?gren's syndrome and related autoimmune diseases. Results of a quantitative immunoassay using a highly purified antigen

A quantitative immunoassay using a highly purified antigen from HeLa cells has allowed us to detect antibodies to SSB/La in 11/20 patients with primary Sj?gren's syndrome (SS), 15/33 with SLE, and 11/35 with progressive systemic sclerosis (PSS). However, positive results were found in only 2/12 patients with idiopathic Raynaud's disease and 2/20 with rheumatoid arthritis, including 4 with secondary SS. Anti-SSB/La were associated with extraglandular manifestations in primary SS, and with a diffuse sclerodermic pattern in PSS. In SS, SLE and PSS, a positive anti-SSB/La test was strongly associated with nodal or spleen enlargement and with an increased level of gamma-globulins. A direct association was also found with positive tests for rheumatoid factors, anti-SSA/Ro and anti-Scl 70. An inverse relationship was however found with anti-nRNP +/- Sm and anticentromere antibodies. Our data suggest that anti-SSB/La antibodies can be regarded as a marker of B-lymphocyte activation in patients with either primary SS, SLE or PSS.