Sj?gren’s syndrome (SS) is a chronic autoimmune disorder of the exocrine glands with clinical manifestation of dry eyes and dry mouth. The pathogenesis of SS is poorly understood, and efficient therapy is currently lacking. Therefore, an appropriate animal model recapitulating the key features of SS could be of profound value. Although several murine models have been established and evaluated, some of these models may develop other non-SS symptoms simultaneously. Herein, an autoimmunization-induced C57BL/6 female mouse model is evaluated. This mouse model exhibited less saliva secretion and swollen salivary gland with severe inflammation in the submandibular gland. Furthermore, apoptosis and pro-inflammatory cytokines were significantly increased and the expression of aquaporin 5, a water channel protein, was decreased and restricted to the basolateral membranes in acinar cells, indicating the weakening of water transport. Besides, autoantibodies such as Ro, La and other anti-nuclear autoantigens were found to be tremendously increased. The expression of M3 muscarinic receptor (M3R) increased in the acinar cells. This can be described as a compensatory expression due to the long term blockage from the autoantibodies which is similar in the SS patients. The characteristics of this model recapitulate the key features of human SS. Dendrobium officinale is an herbal medicine with yin-nourishing effect and clinically used in China as a health tonic to promote body fluid production. The polysaccharides extracted from Dendrobium officinale (DP) consisted of 6 monosaccharides: mannose, glucose, galactose, arabinose, xylose and glucuronic acid in the ratio of 10:0.25:1.2:4.7:1.3:1.4. DP was found to be protective on this experimental SS model. Specifically, administration of DP 20 mg/ml significantly prevented the chaos of immune responses and imbalance of pro-inflammatory cytokines. Our previous work also demonstrated that DP can promote saliva production in both SS patients and SS model. Therefore, we investigated the M3R activation induced by DP treatment. In contrast to the acute activation by acetylcholine, DP exerts slow, but long term activation on M3R. The botanical monosaccharides xylose and arabinose cannot be detected in the cell lysate, indicating that hydrolyzed DP did not permeate the cell membrane. Further investigations suggested that DP can inhibit the apoptosis induced by the addition of recombinant TNF-α on the human salivary gland epithelial cell line A-253. By investigating the potential mechanisms, we found that DP treatment can inhibit the apoptotic factors including the NF-κB activation, increased reactive oxygen species, decreased mitochondrial membrane potential and prolonged mitogen-activated protein kinase activation. The results suggested that DP may interfere with the TNF-α pathway and its receptor since DP did not permeate the cell membrane. / published_or_final_version / Chinese Medicine / Doctoral / Doctor of Philosophy

Patients with primary Sjögren’s syndrome (pSS) are at increased risk of developing malignant lymphoma. The studies in this thesis aim at broadening our understanding of the association between these two conditions. Germinal centre (GC)-like structures were found in minor salivary gland biopsies taken at the time of pSS diagnosis in 25% of 175 studied patients. Lymphoma development was observed in 86% of the GC-positive pSS patients and 14% of the GC-negative patients. GC-like structures in salivary gland biopsies at pSS diagnosis might identify pSS patients at high risk for later lymphoma development. We used the National Patient Register and the Cancer Register to identify pSS patients with lymphoid malignancy for the following studies. The lymphoma tissues were reviewed and classified according to the WHO classification. In a study of 79 patients with available lymphoma tissues, we identified histopathological and clinical features compatible with IgG4-related disease (IgG4-RD) in one patient (1.3%). Histological features of IgG4-RD in lymphoma tissue in patients with an initial pSS diagnosis seem to be rare but, if present, may indicate underlying IgG4-RD. We identified and compared pSS patients with (n=18/17%) and without (n=87) pre-existing lymphoma at pSS diagnosis and found similar pSS characteristics in both groups. Mucosa-associated lymphoid tissue (MALT) lymphoma in salivary glands was more common in patients with pre-existing lymphoma. The findings support the removal of pre-existing lymphoma as a general exclusion criterion for a pSS diagnosis in classification criteria. Further, the findings suggest an investigation for pSS in patients presenting with MALT lymphoma in salivary glands. We compared the distribution of lymphoma subtypes with a general population reference. Both diffuse large B-cell lymphoma (DLBCL) (32%) and marginal zone lymphoma (MZL) (31%) were common, but only MZL (MALT lymphomas) occurred at an increased relative frequency compared to the general population. Men constituted 15% of 105 pSS patients with lymphoma. Men had a shorter time between the pSS and lymphoma diagnoses and more often had lymphoma in the salivary glands compared with women. Increased awareness of signs of lymphoma in salivary glands already during the first years after pSS diagnosis is justified in men with pSS.

A síndrome de Sjögren primária (SSp) é uma doença crônica autoimune sistêmica que pode levar à hipossalivação e afetar negativamente o ambiente oral. Os objetivos deste estudo foram detectar a influência da SSp nos níveis de biomarcadores inflamatórios na saliva e no fluido gengival nas amostras de pacientes com periodontite crônica, avaliar o efeito do tratamento periodontal não cirúrgico sobre os valores do índice clínico de avaliação da atividade sistêmica de pacientes com SSp e do índice reportado pelo paciente com SSp. Amostras de fluido gengival, saliva e os parâmetros clínicos periodontais que consistiram de medida da profundidade de sondagem (PS), nível clínico de inserção (NCI), sangramento à sondagem (SS) e índice de placa (IP) foram coletadas no início do estudo e 45 dias após a terapia periodontal não-cirúrgica de pacientes sistemicamente saudáveis com periodontite crônica (PC, n = 7) e pacientes com SSp e periodontite crônica (SP, n = 7). Pacientes periodontalmente saudáveis com SSp (SC, n = 7) e sistemicamente saudáveis (C, n = 7) também foram avaliados no início do estudo. Os grupos C, PC e SC foram pareados em gênero, idade e critério socioeconômico com o grupo SP. Os níveis de interleucina-8 (IL-8), IL-10 e IL-1ß foram avaliados por ensaio multiplex. Os níveis de atividade da doença foram medidos usando o Gold Standard da literatura chamado Índice Eular de atividade da síndrome de Sjögren (ESSDAI). Já para avaliação dos sintomas reportados pelo paciente com SSp foi utilizado o Índice Eular reportado pelo paciente com Sjögren (ESSPRI). Os parâmetros clínicos melhoraram após a terapia periodontal (p <0,05). No entanto, o NCI em pacientes com SSp não melhorou significativamente após a terapia (p> 0,05). Houve um aumento nos níveis de IL-1ß, IL-8 e diminuição dos níveis de IL-10 nas amostras de saliva de pacientes do grupo SC em comparação ao grupo C (p <0,05). Já em relação ao fluido gengival, pacientes do grupo SC tiveram maiores níveis de IL-1ß em comparação com o grupo C (p<0,05). Além disso, o tratamento periodontal não cirúrgico resultou num aumento dos níveis de IL-10 no fluido gengival no grupo SP e grupo PC em relação ao valor basal (p <0,05). O fluxo salivar foi significativamente aumentado após o tratamento periodontal apenas em pacientes do grupo SP (p = 0,039). Além disso, o tratamento periodontal não influenciou o índice ESSDAI (p = 0,35) e levou a uma diminuição significativa no índice ESSPRI (p = 0,03). Os presentes dados demonstraram que a SSp influencia os níveis salivares e de fluido gengival de biomarcadores inflamatórios em favor de um perfil próinflamatório, no entanto, este perfil parece não aumentar susceptibilidade dos indivíduos SSp à destruição periodontal. Além disso, os presentes dados demonstraram que o tratamento periodontal não-cirúrgico tem um impacto positivo sobre o fluxo salivar e sobre o índice ESSPRI de pacientes com SSp. Sugere-se assim que o tratamento periodontal pode melhorar a qualidade de vida de indivíduos com SSp. / Primary Sjögren\'s syndrome (pSS) is a chronic systemic autoimmune disease that might lead to hyposalivation and negatively affect the oral environment. The aims of this study were to detect the influence of pSS on the levels of inflammatory biomarkers in salivary and gingival crevicular fluid (GCF) samples of patients with chronic periodontitis and to evaluate the effect of non-surgical periodontal treatment on the disease activity index of patients with pSS, and on the reported index of patients with pSS. GCF and salivary samples and clinical parameters consisting of measuring probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP) and plaque index (PI) were collected at baseline and 45 days after non-surgical periodontal therapy from systemically healthy patients with chronic periodontitis (PC, n=7) and patients with pSS with chronic periodontitis (SP, n=7). Periodontally healthy patients with pSS (SC, n=7) and systemically healthy (C, n=7) were also evaluated at baseline. The groups C, PC and SC were pared on gender, years and socioeconomic status with the SP group. The levels of interleukin-8 (IL-8), IL-10, and IL-1ß were measured by using multiplex immunoassays. Disease activity levels were measured by using the Gold Standard called Eular Sjögren\'s syndrome disease activity index (ESSDAI). Also to evaluate the symptoms reported by the pacients with pSS we used the Eular Sjögren\'s syndrome patient reported index (ESSPRI). The clinical parameters improved significantly after periodontal therapy (p<0.05). However, CAL in pSS patients was not statistically improved after therapy (p>0.05). There was an increased expression of IL-1ß, IL-8 and decreased levels of IL-10 in the salivary samples of patients in the group SC compared to the group C (p<0.05). The GCF, patients in the group SC had bigger levels of IL-1ß in comparation with the C group (p<0.05). Moreover, nonsurgical periodontal treatment resulted in increased levels of IL-10 on GCF in the groups SP and PC in relation to the baseline (p<0.05). Salivary flow was significantly increased post-treatment only in the SP\'s group patients (p=0.039). In addition, periodontal treatment did not influence ESSDAI index (p=0.35) and led to a statistically significant decrease on the ESSPRI index (p=0.03). The present data demonstrated that pSS influences the salivary and GCF levels of inflammatory biomarkers in favour of a proinflammatory profile, however, this profile might doesn\'t increase the susceptibility of pSS subjects to periodontal breakdown. In addition, the present data demonstrated that non-surgical periodontal treatment has a positive impact on the salivary flow and ESSPRI index of pSS patients. Thus suggesting that periodontal treatment may improve the quality of life of pSS subjects.

A síndrome de Sjögren primária (SSp) é uma doença crônica autoimune sistêmica que pode levar à hipossalivação e afetar negativamente o ambiente oral. Os objetivos deste estudo foram detectar a influência da SSp nos níveis de biomarcadores inflamatórios na saliva e no fluido gengival nas amostras de pacientes com periodontite crônica, avaliar o efeito do tratamento periodontal não cirúrgico sobre os valores do índice clínico de avaliação da atividade sistêmica de pacientes com SSp e do índice reportado pelo paciente com SSp. Amostras de fluido gengival, saliva e os parâmetros clínicos periodontais que consistiram de medida da profundidade de sondagem (PS), nível clínico de inserção (NCI), sangramento à sondagem (SS) e índice de placa (IP) foram coletadas no início do estudo e 45 dias após a terapia periodontal não-cirúrgica de pacientes sistemicamente saudáveis com periodontite crônica (PC, n = 7) e pacientes com SSp e periodontite crônica (SP, n = 7). Pacientes periodontalmente saudáveis com SSp (SC, n = 7) e sistemicamente saudáveis (C, n = 7) também foram avaliados no início do estudo. Os grupos C, PC e SC foram pareados em gênero, idade e critério socioeconômico com o grupo SP. Os níveis de interleucina-8 (IL-8), IL-10 e IL-1ß foram avaliados por ensaio multiplex. Os níveis de atividade da doença foram medidos usando o Gold Standard da literatura chamado Índice Eular de atividade da síndrome de Sjögren (ESSDAI). Já para avaliação dos sintomas reportados pelo paciente com SSp foi utilizado o Índice Eular reportado pelo paciente com Sjögren (ESSPRI). Os parâmetros clínicos melhoraram após a terapia periodontal (p <0,05). No entanto, o NCI em pacientes com SSp não melhorou significativamente após a terapia (p> 0,05). Houve um aumento nos níveis de IL-1ß, IL-8 e diminuição dos níveis de IL-10 nas amostras de saliva de pacientes do grupo SC em comparação ao grupo C (p <0,05). Já em relação ao fluido gengival, pacientes do grupo SC tiveram maiores níveis de IL-1ß em comparação com o grupo C (p<0,05). Além disso, o tratamento periodontal não cirúrgico resultou num aumento dos níveis de IL-10 no fluido gengival no grupo SP e grupo PC em relação ao valor basal (p <0,05). O fluxo salivar foi significativamente aumentado após o tratamento periodontal apenas em pacientes do grupo SP (p = 0,039). Além disso, o tratamento periodontal não influenciou o índice ESSDAI (p = 0,35) e levou a uma diminuição significativa no índice ESSPRI (p = 0,03). Os presentes dados demonstraram que a SSp influencia os níveis salivares e de fluido gengival de biomarcadores inflamatórios em favor de um perfil próinflamatório, no entanto, este perfil parece não aumentar susceptibilidade dos indivíduos SSp à destruição periodontal. Além disso, os presentes dados demonstraram que o tratamento periodontal não-cirúrgico tem um impacto positivo sobre o fluxo salivar e sobre o índice ESSPRI de pacientes com SSp. Sugere-se assim que o tratamento periodontal pode melhorar a qualidade de vida de indivíduos com SSp. / Primary Sjögren\'s syndrome (pSS) is a chronic systemic autoimmune disease that might lead to hyposalivation and negatively affect the oral environment. The aims of this study were to detect the influence of pSS on the levels of inflammatory biomarkers in salivary and gingival crevicular fluid (GCF) samples of patients with chronic periodontitis and to evaluate the effect of non-surgical periodontal treatment on the disease activity index of patients with pSS, and on the reported index of patients with pSS. GCF and salivary samples and clinical parameters consisting of measuring probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP) and plaque index (PI) were collected at baseline and 45 days after non-surgical periodontal therapy from systemically healthy patients with chronic periodontitis (PC, n=7) and patients with pSS with chronic periodontitis (SP, n=7). Periodontally healthy patients with pSS (SC, n=7) and systemically healthy (C, n=7) were also evaluated at baseline. The groups C, PC and SC were pared on gender, years and socioeconomic status with the SP group. The levels of interleukin-8 (IL-8), IL-10, and IL-1ß were measured by using multiplex immunoassays. Disease activity levels were measured by using the Gold Standard called Eular Sjögren\'s syndrome disease activity index (ESSDAI). Also to evaluate the symptoms reported by the pacients with pSS we used the Eular Sjögren\'s syndrome patient reported index (ESSPRI). The clinical parameters improved significantly after periodontal therapy (p<0.05). However, CAL in pSS patients was not statistically improved after therapy (p>0.05). There was an increased expression of IL-1ß, IL-8 and decreased levels of IL-10 in the salivary samples of patients in the group SC compared to the group C (p<0.05). The GCF, patients in the group SC had bigger levels of IL-1ß in comparation with the C group (p<0.05). Moreover, nonsurgical periodontal treatment resulted in increased levels of IL-10 on GCF in the groups SP and PC in relation to the baseline (p<0.05). Salivary flow was significantly increased post-treatment only in the SP\'s group patients (p=0.039). In addition, periodontal treatment did not influence ESSDAI index (p=0.35) and led to a statistically significant decrease on the ESSPRI index (p=0.03). The present data demonstrated that pSS influences the salivary and GCF levels of inflammatory biomarkers in favour of a proinflammatory profile, however, this profile might doesn\'t increase the susceptibility of pSS subjects to periodontal breakdown. In addition, the present data demonstrated that non-surgical periodontal treatment has a positive impact on the salivary flow and ESSPRI index of pSS patients. Thus suggesting that periodontal treatment may improve the quality of life of pSS subjects.

Sjögren's Syndrome (SS) is an autoimmune disease that causes extreme dryness, or sicca,of the eyes and mouth, as well as other potential drying of the throat and intestines. Speech, voice, and swallowing problems are common in individuals with SS. Therefore, this study examined the possible changes in acoustic characteristics of monophthongs (/i, æ, α, u, ʌ/) in eight females with SS following laryngeal hydration treatments. An ABAB experimental design was implemented. Treatment consisted of nebulized isotonic saline immediately following completion of audio-recordings. Using acoustic analysis software the duration, formant frequencies, and vowel space area (VSA) was calculated for the participant's vowel productions. Overall the mean duration of the participant's vowel productions increased slightly from baseline measurements through the last treatment phase. Minimal deviations were observed in first and second formant frequency values throughout the study. Only minor differences were found in the participant's VSA from baseline phase of data collection through the final treatment phase, with most of these differences due to a change in the first formant of the /æ/ vowel. Despite the need for future research, the findings of this study increase understanding into how SS impacts speech production.

The purpose of this study was to analyze and quantify the effects of a nebulized saline treatment on speech production in eight females with Primary Sjögren's Syndrome (SS). The duration, formant frequency onset and offset, and slope were measured to determine the quality of participants' production of diphthongal American English vowels. Acoustic data were examined before treatment began, immediately following treatment, and during a one-week follow-up to determine the effects of a laryngeal hydration program that used nebulized saline to increase hydration of structures in the vocal tract. The vowels produced during the initial baseline condition were acoustically relatively similar to the productions of typical speakers not diagnosed with SS. Although some differences in mean vowel duration and formant frequency values were found in the recorded vowel productions, results indicated that the participants' vowel productions remained relatively stable across the different phases of treatment. The absence of large treatment effects, in terms of vowel acoustics, may be due to the possibility that although the dryness associated with SS is an irratant for speakers, it may not affect their ability to produce diphthongal vowels in a significant manner.

Le syndrome de Gougerot-Sjögren (SGS) est une maladie auto-immune systémique. Il se caractérise principalement par une infiltration lymphocytaire des glandes salivaires (GS) et lacrymales responsable d’une sécheresse buccale et oculaire. Par ailleurs,les Toll-like récepteurs (TLR) endosomaux – notamment le TLR9 qui reconnait l’acide désoxyribonucléique (ADN) microbien mais aussi, dans certaines conditions, l’ADN du soi –s’avèrent être importants pour l’activation des lymphocytes B (LB) lors du lupus, une maladie proche du SGS. Nos travaux montrent que la stimulation du TLR9 chez les LB transitionnels,des LB immatures fraichement émigrés de la moelle osseuse, favorise leur différenciation selon la voie des LB de la zone marginale, et entraine la sécrétion d’auto-anticorps. L’analyse des LB infiltrant les GS lors du SGS révèle que ce phénomène pourrait être impliqué dans la physiopathologie de cette maladie. De plus, nous montrons que LL37, un peptide produit dans les GS, pourrait participer à l’activation du TLR9 des LB transitionnels. Enfin, nous avons mis en évidence une inattendue expression du TLR9 à la surface des LB. Si l’étude des conséquences fonctionnelles de cette localisation reste à poursuivre, elle semble avoir un effet négatif sur la stimulation du TLR9 endosomal. En conclusion, ces résultats suggèrent que leTLR9 puisse être une nouvelle cible thérapeutique lors du SGS. / Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease. It is mainly characterized by B cell and T cell infiltration in lacrimal and salivary glands (SG) responsible for eye and mouth dryness. In addition, endosomal Toll-like receptors (TLR) – especially TLR9 which recognizes microbial deoxyribonucleic acid (DNA) and also, under certain conditions, self DNA – are important for B cell activation during lupus, a disease close topSS. Our work shows that TLR9 stimulation on transitional B cells, immature B cells freshly emigrated from bone marrow, promotes their differentiation into marginal zone B cell pathway and drives to auto-antibodies production. Analysis of infiltrating B cells in pSS SG reveals that this phenomenon might be involved in the pathogenesis of the disease.Furthermore, we show that LL37, a peptide produced in the SG, could participate in TLR9activation of transitional B cells. Finally, we demonstrated an unexpected TLR9 expression on B cell surface. If the functional consequences of this localization remain to be more precisely evaluated, it seems that cell surface TLR9 has a negative effect on endosomal TLR9 stimulation. In conclusion, these results suggest TLR9 could be a new therapeutic target incase of pSS.

Primary Sjögren's Syndrome (SS) is an autoimmune disease that causes dehydration of the eyes, mouth, and throat. Individuals with Primary SS are at risk for voice problems associated with vocal fold dehydration. Topical hydration treatments show promise in reducing the negative effects of vocal fold dehydration on voice production. However, no studies have examined the preventive effects of topical hydration treatments on voice production in individuals at risk for vocal fold dehydration. The purpose of this study was to quantify the effects of a topical vocal fold hydration treatment on voice production in individuals with Primary SS using the Cepstral Spectral Index of Dysphonia (CSID). Eight participants with Primary SS completed an eight-week study involving twice-daily audio recordings of sustained vowels and the Rainbow Passage. Participants received 9 mL of nebulized isotonic saline (0.9% Na+Cl-) immediately following morning and evening voice recordings during weeks 3, 4, 7, and 8 using an ABAB within-subjects experimental design. Baseline CSID values were in the mild range. Although CSID values decreased (improved) during the treatment phases of the study, no statistically significant changes were observed from baseline to treatment. Statistically significant correlations were observed among CSID values and patient-based ratings of vocal effort and dryness, which did improve with treatment (p < .05). These results indicate that topical saline treatments may prevent and treat some voice problems associated with vocal fold dehydration in at-risk populations.

The purpose of this study was to examine the effectiveness of relative fundamental frequency (RFF) in quantifying voice disorder severity and possible change with treatment in individuals with Primary Sjögren's Syndrome (SS). Participants completed twice-daily audio recordings during an ABAB within-subjects experimental study investigating the effects of nebulized saline on voice production in this population. Voice samples of the Rainbow Passage from seven of the eight individuals with Primary SS involved in a larger investigation met inclusion criteria for analysis, for a total of 555 tokens. The results indicated that RFF values for this sample were similar to previously reported RFF values for individuals with voice disorders. RFF values improved with nebulized saline treatment but did not fall within the normal range for typical speakers. These findings were similar to other populations of voice disorders who experienced improvement, but not complete normalization, of RFF with treatment. Patient-based factors, such as age and diagnosis as well as measurement and methodological factors, might affect RFF values. The results from this study indicate that RFF is a potentially useful measure in quantifying voice production and disorder severity in individuals with Primary SS.

INTRODUÇÃO: A síndrome de Sjögren primária (SSp) é uma doença autoimune inflamatória crônica que afeta principalmente as glândulas exócrinas, levando aos sintomas de síndrome sicca. O olho seco é uma das características mais importantes dessa síndrome e um estudo recente relatou redução da atividade da DNase I em lágrimas de pacientes com olho seco de várias etiologias. Portanto, postulamos que pacientes com SSp possam ter anticorpos direcionados à DNase I. MÉTODOS: Avaliamos em um estudo de corte transversal 85 pacientes com SSp (conforme os critérios de classificação do American European Consensus Group Criteria, 2002), 50 pacientes com artrite reumatoide (AR) (American College of Rheumatology Criteria/ 1987) sem sintomas de síndrome sicca e 88 voluntários saudáveis. A reatividade IgG anti-DNase I foi detectada por ELISA utilizando a enzima de pâncreas bovino como antígeno e confirmada por Imunoblotting. RESULTADOS: A idade e sexo foram comparáveis nos três grupos (p > 0,05). A anti-DNase I foi detectada em 43,5% dos pacientes com SSp, conforme determinado por ELISA. Em contraste, essa reatividade estava ausente em todos os pacientes com AR (p= 0,0001). Comparações adicionais dos pacientes com SSp com (n= 37) e sem (n= 48) anti-DNase I revelaram que o primeiro grupo tinha níveis séricos de IgG mais altos (2293,2 ± 666,2 vs. 1483,9 ± 384,6 mg/dL, p= 0,0001) e uma frequência maior de leucopenia não induzida por drogas (43% vs. 19%, p= 0,02). A análise de regressão logística multivariada mostrou que apenas os níveis de IgG foram independentemente associados com o anti-DNase I. CONCLUSÃO: Descrevemos uma alta frequência de anticorpos anti-DNase I em pacientes com SSp associados a níveis séricos de IgG mais elevados. A falta dessa reatividade em pacientes com AR sem sintomas de sicca sugere que esse anticorpo pode ser útil no diagnóstico diferencial dessas doenças / INTRODUCTION: Primary Sjögren\'s syndrome (pSS) is a chronic inflammatory autoimmune disease that mainly affects exocrine glands. Dry eye is one of the most important features of this syndrome and a recent study reported reduced DNase I activity in tears of patients with dry eye of various etiologies. We therefore postulated that patients with pSS may have antibodies targeting DNase I. METHODS: We have evaluated in a cross-sectional study 85 pSS patients (American European Consensus Group Criteria/ 2002), 50 rheumatoid arthritis (RA) patients (American College of Rheumatology Criteria/ 1987) without sicca symptoms and 88 healthy volunteers. The IgG anti-DNase I reactivity was detected by ELISA using bovine pancreas enzyme as antigen and confirmed by Immunoblotting. RESULTS: Age/ gender were comparable in the three groups (p > 0.05). Anti-DNase I was detected in 43.5% of the pSS patients as determined by ELISA. In contrast, this reactivity was absent in all RA patients (p= 0.0001). Further comparison of pSS patients with (n= 37) and without (n= 48) anti-DNase I revealed that the former group had higher IgG serum levels (2293.2 ± 666.2 vs. 1483.9 ± 384.6 mg/dL, p= 0.0001) and a higher frequency of non-drug induced leukopenia (43% vs. 19%, p= 0.02). A multivariate logistic regression analysis identified that only IgG levels were independently associated with anti-DNase I. CONCLUSION: We describe a high frequency of anti-DNase I antibodies in pSS patients associated with higher serum IgG levels. The lack of this reactivity in RA patients without sicca symptoms suggests that this antibody may be helpful in the differential diagnosis of these diseases