Secondary Sjögren's Syndrome Research Articles

AB0427 Clinical and laboratory findings in patients with late-onset sle and correlations with il6 concentrations

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune rheumatic disease that usually develops in women aged 18-50 years. It is known that age at onset modifies the clinical manifestations of SLE,...

SAT0237 Usefulness of the mayor salivary gland ultrasonography in the evaluation of the patient affected by SICCA syndrome

ObjectivesThis study aims to describe the sonographic abnormalities of the major salivary glands in patients evaluated for sicca syndrome.Methods110 consecutive patients with sicca syndrome, 104 females and 6 males, aged...

Immunogenicity of influenza H1N1 vaccination in mixed connective tissue disease: effect of disease and therapy

OBJECTIVE:To assess the potential acute effects regarding the immunogenicity and safety of non-adjuvanted influenza A H1N1/2009 vaccine in patients with mixed connective tissue disease and healthy controls.METHODS:Sixty-nine mixed connective tissue disease patients that were confirmed by Kasukawa's classification criteria and 69 age- and gender-matched controls participated in the study; the participants were vaccinated with the non-adjuvanted influenza A/California/7/2009 (H1N1) virus-like strain. The percentages of seroprotection, seroconversion, geometric mean titer and factor increase in the geometric mean titer were calculated. The patients were clinically evaluated, and blood samples were collected pre- and 21 days post-vaccination to evaluate C-reactive protein, muscle enzymes and autoantibodies. Anti-H1N1 titers were determined using an influenza hemagglutination inhibition assay. ClinicalTrials.gov: NCT01151644.RESULTS:Before vaccination, no difference was observed regarding the seroprotection rates (p = 1.0) and geometric mean titer (p = 0.83) between the patients and controls. After vaccination, seroprotection (75.4% vs. 71%, p = 0.7), seroconversion (68.1% vs. 65.2%, p = 1.00) and factor increase in the geometric mean titer (10.0 vs. 8.0, p = 0.40) were similar in the two groups. Further evaluation of seroconversion in patients with and without current or previous history of muscle disease (p = 0.20), skin ulcers (p = 0.48), lupus-like cutaneous disease (p = 0.74), secondary Sjögren syndrome (p = 0.78), scleroderma-pattern in the nailfold capillaroscopy (p = 1.0), lymphopenia ≤1000/mm3 on two or more occasions (p = 1.0), hypergammaglobulinemia ≥1.6 g/d (p = 0.60), pulmonary hypertension (p = 1.0) and pulmonary fibrosis (p = 0.80) revealed comparable rates. Seroconversion rates were also similar in patients with and without immunosuppressants. Disease parameters, such as C-reactive protein (p = 0.94), aldolase (p = 0.73), creatine phosphokinase (p = 0.40) and ribonucleoprotein antibody levels (p = 0.98), remained largely unchanged pre and post-vaccination. No severe side effects were reported.CONCLUSIONS:The non-adjuvanted influenza A/H1N1 vaccination immune response in mixed connective tissue disease patients is adequate and does not depend on the disease manifestations and therapy.

P8-04 Immunological profile of plasmacytoid dendritic cells and mast cells in Sjogren's syndrome

Although the role of lymphocytes in the pathology of Sjogren's Syndrome (SS) has been investigated, the role plasmacytoid dendritic cells (PDCs) and mast cells (MCs) remains poorly understood.Lip biopsy specimen from 178 SS and 7 Sicca syndrome (Sicca) were analyzed for histological scores and density of PDCs and MCs. Lymphocytes infiltration, acinar atrophy and intralobular fibrosis were observed with increased pDCs and MCs in SS compared to Sicca patients. Positive correlation was observed in pDCs density with lymphocytes infiltration and MCs density with intralobular fibrosis in primary SS but not in secondary SS. Within the primary SS, CXCL13+ cells density positively correlated with lymphocyte infiltration and pDCs density. Double staining with anti-CXCL13 and anti-CD68 revealed that majority of CXCL13+ cells are macrophages, and that pDCs and CXCL13+ cells are localized at the surrounding area of the duct. Our data suggests the role of PDCs in lymphocyte infiltration and MCs in intralobular fibrosis in primary SS. Moreover, CXCL13 expression suggests the involvement of multiple lineage cells in the early stage of the disease, and MCs in the mid to late stage.

Validation of different sets of criteria for the diagnosis of Sjögren’s syndrome in Japanese patients

To validate the revised Japanese Ministry of Health criteria for the diagnosis of Sjögren's syndrome (SS) (JPN) (1999), The American-European Consensus Group classification criteria for SS (AECG) (2002), and American College of Rheumatology classification criteria for SS (ACR) (2012). The study subjects were 694 patients with SS or suspected SS who were followed-up in June 2012 at ten hospitals that form part of the Research Team for Autoimmune Diseases, The Research Program for Intractable Disease by the Ministry of Health, Labor and Welfare (MHLW). All patients had been checked for all four criteria of the JPN (pathology, oral, ocular, anti-SS-A/SS-B antibodies). We studied the clinical diagnosis made by the physician in charge and the satisfaction of the above criteria. Of the 694 patients, 499 patients did not have other connective tissue diseases (CTDs). SS was diagnosed in 476 patients (primary SS in 302, secondary SS in 174), whereas non-SS was diagnosed in 218 patients (without other CTDs in 197, with other CTDs in 21) by the physician in charge. The sensitivities of JPN, AECG, and ACR in the diagnosis of all forms of SS (both primary and secondary SS) were 79.6, 78.6, and 77.5%, respectively, with respective specificities of 90.4, 90.4, and 83.5%. The sensitivities of the same systems in the diagnosis of primary SS were 82.1, 83.1, and 79.1%, respectively, with specificities of 90.9, 90.9, and 84.8%, respectively. The sensitivities of the same systems in the diagnosis of secondary SS were 75.3, 70.7, and 74.7%, respectively, with specificities of 85.7, 85.7, and 71.4%, respectively. The sensitivity of JPN to all forms of SS and secondary SS, the sensitivity of AECG to primary SS, and the specificities of JPN and AECG for all forms of SS, primary SS, and secondary SS were highest in the diagnosis of SS in Japanese patients. These results indicate that the JPN criteria for the diagnosis of SS in Japanese patients are superior to ACR and AECG.

Prevalence and predictors of Sjögren's syndrome in a prospective cohort of patients with aqueous-deficient dry eye

AimsTo assess the prevalence and determine predictors of Sjögren's syndrome (SS) in patients with clinically significant aqueous-deficient dry eye.MethodsPatients enrolled in an industry-sponsored, multicentre clinical trial (NCT00784719) were assessed prospectively...

Isolated rheumatoid arthritis-associated cerebral vasculitis: A diagnostic challenge

Central nervous system involvement in rheumatoid arthritis is uncommon. In order of frequency, published cases have reported rheumatoid nodules, meningeal vasculitis, and cerebral vasculitis (CV). The frequency of vasculitic cerebral involvement in rheumatoid arthritis is unknown. However, it is known that it is more common in patients with seropositive, long-standing rheumatoid arthritis, and in those with concomitant systemic vasculitis. We report the case of a 47-year-old woman with an 11-year history of seropositive rheumatoid arthritis without any extra-articular manifestations, with the exception of secondary Sjogren's syndrome, presenting with mental status changes and tonic-clonic seizures as symptoms of isolated CV. Magnetic resonance imaging (T2) showed hyperintense white-matter lesions in the frontal and temporal lobes, as well as in the hippocampus and cerebellum. Transcranial Doppler ultrasound findings were consistent with CV. Other differential diagnoses were ruled out. The patient responded favorably to methylprednisolone and intravenous gammaglobulin therapy.

A comparison of two clinical methods for measuring saliva in patients with Sjögren's syndrome

Objective. The aim of the present study was to evaluate two different ways of measuring unstimulated and stimulated whole salivary output in the dental clinic, namely by volume (mL/min) and by weight (g/min). Materials and methods. Thirty-one patients diagnosed with Secondary Sjögren's syndrome (SSS) participated in the study. Results. The results showed a large discrepancy between the measurements performed by volume and by weight (p < 0.001) and additionally when taking into account density calculation, especially in individuals with low salivary secretion rate. Conclusion. It is suggested that weight measurement of saliva should be more routinely implemented, especially in patients with reduced salivary secretion.

Olho seco e Sjögren secundário na artrite reumatóide

OBJECTIVE: To examine the prevalence of keratoconjuntivitis sicca and secondary Sjogren syndrome (SS) in patients with RA from Southern Brazil and to analyze their relationship with RA duration, activity and patient's functional class. Patients with rheumatoid arthritis (RA) may have keratoconjuntivitis sicca that can be considered an extra articular manifestation of this disease. METHODS: We studied 82 RA patients for sicca symptoms, Schirmer test, DAS-28 (RA activity index) and functional class. RESULTS: There were eye sicca symptoms in 57.3%, positive Schirmer test in 41.2% and Secondary SS in 24.3%. The presence of a positive Schirmer test or the secondary SS had no relation with disease duration (p=0.65 and 0.80), RA activity (p=0,42 and 0,25) and neither with the patient's functional class (p= 0.84 and 0.79). CONCLUSION: There is a high prevalence of sicca syndrome in RA patients; one fourth of them have secondary SS. Secondary SS and sicca syndrome occurrence is independent of underlying RA activity, duration and cumulative damage.

Sexual dysfunction in rheumatoid arthritis patients: arthritis and beyond

Rheumatoid arthritis treatment has been shown to improve quality of life. There is little data regarding the impact of the disease and treatments on sexual function. The aim of this study was to describe the results of an assessment of sexual activity/sexual satisfaction of rheumatoid arthritis patients, identify the sexual dysfunction features, and assess their association with disease activity/disease activity parameters and other systemic risk factors/comorbidities. Consecutive rheumatoid arthritis patients attending the outpatient rheumatology clinic completed the multidimensional patient-reported outcome measures questionnaire. There are three questions screening for sexual dysfunction: patients who ticked any of the boxes were further assessed. Men completed the Sexual Health Inventory for Men; whereas women completed the Female Sexual Function Index. All patients underwent clinical assessment of disease activity parameters and cardiovascular risk. Among 231 rheumatoid arthritis patients included in this study, 49/91 (53.8%) men and 64/140 (45.7%) women reported sexual dysfunction. Among men, erectile dysfunction significantly correlated (p < 0.01) with pain score, cardiovascular disease, age, disease activity, fatigue score, intramuscular steroid injection, and tender joint count. Among women, sexual dysfunction was significantly correlated (p < 0.01) with occurrence of secondary Sjogren's syndrome, pain score, cardiovascular disease, hip joint involvement, disease activity, and tender joint count. Sexual dysfunction is common among rheumatoid arthritis patients. Erectile dysfunction in men, and problems with orgasm, arousal, and satisfaction in women, were the most prevalent manifestations. The significant correlation of sexual dysfunction with CVD may help to identify patients at high risk of cardiovascular disorders.

Reflections in the assessment of secondary Sjogren's syndrome

Reflections in the assessment of secondary Sjogren's syndrome

Prognostic factors for the clinical severity of keratoconjunctivitis sicca in patients with Sjögren's syndrome

AimsTo determine whether prognostic immunological profiles predict the severity of keratoconjunctivitis sicca (KCS) in patients with Sjögren's syndrome (SS).Methods121 patients diagnosed with SS and followed for at least 1 year...

In Vivo Confocal Microscopy of Meibomian Glands in Sjögren's Syndrome

To evaluate morphologic changes in meibomian glands (MGs) and the status of periglandular inflammation in patients with primary and secondary Sjögren's Syndrome (SS) using in vivo confocal laser microscopy (LSCM). Twenty patients with primary SS (SSI), 25 with secondary SS (SSII), 20 with MG dysfunction (MGD), and 25 age- and gender-matched control subjects were enrolled consecutively. Each participant completed an Ocular Surface Disease Index questionnaire and underwent a full eye examination, including tear film break-up time (BUT), fluorescein and lissamine green staining, Schirmer test, and an LSCM examination of the MGs, the last to determine acinar unit density and diameter, glandular orifice diameters, meibum secretion reflectivity, inhomogeneous appearance of glandular interstice, and acinar wall. All parameters indicated statistically significant differences among groups (P < 0.001, Kruskal-Wallis test). LSCM demonstrated no differences between SSI and SSII (Mann-Whitney U test). Compared with control subjects, SS subjects' MGs showed more periglandular inflammation and higher secretion reflectivity (P < 0.001, Mann-Whitney U test). Compared with MGD patients, SS patients' MGs had higher acinar density, smaller diameters, greater density of periglandular inflammatory cells, and lower secretion reflectivity (P < 0.001, Mann-Whitney U test). In SS patients, the two measured confocal signs of inflammation were significantly interrelated and correlated with corneal fluorescein staining (P ≤ 0.01, Spearman correlation coefficient). Acinar density and diameters were strongly correlated among themselves (P < 0.001) and with BUT (P < 0.05). LSCM is capable of effectively revealing morphologic and inflammatory changes in MGs and showed discernible patterns of MG abnormalities in SS and MGD not easily distinguishable by the usual clinical exams.

Follistatin-like protein 1 is elevated in systemic autoimmune diseases and correlated with disease activity in patients with rheumatoid arthritis

IntroductionFollistatin-like protein 1 (FSTL1) is a proinflammation mediator implicated in arthritis in rodent animal models. The present study is aimed at assessing FSTL1 levels in systemic autoimmune diseases and correlating them with disease activity in patients with rheumatoid arthritis (RA).MethodsSerum FSTL1 levels from 487 patients with systemic autoimmune diseases and 69 healthy individuals were measured by enzyme-linked immunosorbent assay (ELISA). FSTL1 expression in synovial fluid (SF) and synovial tissues (STs) was determined by ELISA, immunohistochemistry, real-time polymerase chain reaction (RT-PCR) and western blot analysis in RA patients and trauma controls. FSTL1 levels in fibroblast-like synoviocytes (FLSs) from RA patients were determined by real-time PCR and western blot analysis.ResultsSerum FSTL1 levels were significantly elevated in patients with RA, ulcerative colitis, systemic lupus erythematosus, Sjögren's syndrome (SS), systemic sclerosis and polymyositis/dermatomyositis. Serum FSTL1 levels in the RA and secondary SS patients were substantially higher than those in other patients. Serum FSTL1 levels were increased in early RA, rheumatoid factor (RF)- and anti-cyclic citrullinated peptide antibody (ACPA)-negative patients compared to healthy controls. Moreover, serum FSTL1 concentrations were significantly higher in long-standing RA patients than in early RA patients and in the RF- and ACPA-positive RA patients than in RF- and ACPA-negative RA patients. Elevated FSTL1 levels in the STs and SF of RA patients were also observed. FSTL1 levels in serum were markedly higher than those in SF in RA patients. The strongest FSTL1 staining was detected in the cytoplasm of synovial and capillary endothelial cells from RA synovium. Furthermore, FSTL1 was induced in FLSs by inflammatory mediators. Importantly, serum FSTL1 levels were correlated with several important biologic and clinical markers of disease activity, including erythrocyte sedimentation rate, C-reactive protein, RF, ACPA, swollen joint count, patient global visual analogue scale score and Disease Activity Score 28 in the adult RA patient population. Notably, serum FSTL1 levels were significantly diminished following successful treatment and clinical improvement.ConclusionsElevated FSTL1 levels reflect not only joint diseases but also inflammation and tissue degradation in systemic autoimmune diseases. Serum FSTL1 levels may thus serve as a serological inflammatory marker of disease activity in RA patients.

Proteome analysis of biological fluids from autoimmune‐rheumatological disorders

Autoimmune-rheumatological diseases are worldwide distributed disorders and represent a complex array of illnesses characterized by autoreactivity (reactivity against self-antigens) of T-B lymphocytes and by the synthesis of autoantibodies crucial for diagnosis (biomarkers). Yet, the effects of the autoimmune chronic inflammation on the infiltrated tissues and organs generally lead to profound tissue and organ damage with loss of function (i.e., lung, kidney, joints, exocrine glands). Although progresses have been made on the knowledge of these disorders, much still remains to be investigated on their pathogenesis and identification of new biomarkers useful in clinical practice. The rationale of using proteomics in autoimmune-rheumatological diseases has been the unmet need to collect, from biological fluids that are easily obtainable, a summary of the final biochemical events that represent the effects of the interplay between immune cells, mesenchymal cells and endothelial cells. Proteomic analysis of these fluids shows encouraging results and in this review, we addressed four major autoimmune-rheumatological diseases investigated through proteomic techniques and provide evidence-based data on the highlights obtained in systemic sclerosis, primary and secondary Sjogren's syndrome, systemic lupus erythematosus and rheumatoid arthritis.

Dermatologic Manifestations of Sjögren Syndrome

Sjögren syndrome (SS) is a chronic autoimmune inflammatory disease that involves primarily the exocrine glands, resulting in their functional impairment. SS typically presents as dry eyes (xerophthalmia) and dry mouth (xerostomia). This process can manifest either as the independent phenomenon of primary SS or as secondary SS when found in the context of another autoimmune process, most commonly rheumatoid arthritis or systemic lupus erythematosus. Nearly half of the patients with SS develop cutaneous manifestations, which may include dry skin (xeroderma), palpable and nonpalpable purpura, and/or urticaria-like lesions. These cutaneous manifestations have been underemphasized because they are often overshadowed by the more prominent sicca symptoms. However, certain skin findings are of paramount clinical and prognostic importance as they confer an increased risk for the development of life-threatening conditions, including multisystem vasculitis and non-Hodgkin lymphoma.OBJECTIVE AND CONCLUSIONS:In this review, the cutaneous manifestations of primary SS are discussed, with an emphasis on those findings that portend an increased risk of mortality.

Primary and Secondary Sjogren-Jones Syndromes—Historical Evolution

©2011 Ethis Communications, Inc. The Ocular Surface ISSN: 1542-0124. Murube J. Primary and secondary SjogrenJones syndromes—historical evolution. 2011;9(1):13-16. ccording to Norman Talal, the history of Sjogren syndrome (SS) can be divided into three phases: clinical (1888-1950), immunologic, and molecular.1 The concept of primary and secondary Sjogren syndrome developed during the transition between the second and third phases. In the last 50 years, since the publications of Jones,2 Bunim,3 and Bloch et al,4 most clinicians and researchers have accepted that SS refers to SS of autoimmune etiopathogenesis, or Sjogren-Jones syndrome. The recognition of the autoimmune basis of the disease opened a new clinical approach.5 The polymorphism of the SSs stimulated several classifications and subclassifications. In 1961, Sjogren6 had already accepted the possible auto-immunologic cause of the sicca syndrome suggested by Jones, Bloch et al, and Bunim,2-4 and he determined that the autoimmunopathies should be divided into collagenoses and adenopathies and that these groups could exist alone or together in various combinations. Clinical differences in SS in the absence or presence of rheumatoid arthritis and of systemic lupus erythematosus had been noted by many clinicians.7-21 The division into primary and secondary SSs had many antecedents, and in 1979 became universally accepted with the publications of Moutsopoulos.22,23 In medical terminology, primary and secondary designations may have several different bases, and have been variously used. In the case of SSs, primary does not mean that it is the origin of the secondary or that it is of more importance than the secondary. In the current terminology of SS, primary and secondary refer to two different etiopathogenic groups or types. De Cremoux et al preferred to say limited rather than primary SS in order to avoid the confusion of the terms.24 Ancochea et al preferred to name these two groups primary and associated SS, the latter being associated with autoimmune diseases and connectivopathies.25 The Triple Classification of Dry Eye proposed describing secondary SS as “SS associated with...” followed by the specific association. This is because sometimes this association is not autoimmunologic, but derives from hormonal, viral, or other causes, or is simply coincident with SS exocrinopathy.26,27 Some authors consider this expression the most appropriate to describe the clinical profile of an SS patient.28

Current Concepts: Mouse Models of Sjögren′s Syndrome

Sjögren's syndrome (SjS) is a complex chronic autoimmune disease of unknown etiology which primarily targets the exocrine glands, resulting in eventual loss of secretory function. The disease can present as either primary SjS or secondary SjS, the latter of which occurs concomitantly with another autoimmune disease such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma, or primary biliary cirrhosis. Current advancements in therapeutic prevention and treatment for SjS are impeded by lack of understanding in the pathophysiological and clinical progression of the disease. Development of appropriate mouse models for both primary and secondary SjS is needed in order to advance knowledge of this disease. This paper details important features, advantages, and pitfalls of current animal models of SjS, including spontaneous, transgenic, knockout, immunization, and transplantation chimera mouse models, and emphasizes the need for a better model in representing the human SjS phenotype.

Casi clinici di due bambini con sindrome di Sjögren primaria

Sjogren-Larsson syndrome (SLS) is a chronic autoimmune disease of unknown etiology most commonly seen in women (male/female ratio 1:9) mainly in the fourth and fifth decades of life. It may occur alone (primary Sjogren syndrome) or in association with other autoimmune diseases (secondary Sjogren syndrome) such as rheumatoid arthritis, systemic lupus erythematosus or systemic sclerosis. We report two cases of SLS. The first case report is about a 10-year-old girl with a history of episodes of tumor, calor and rubor in the back of her toes almost every month, which resolved in 4–5 days without therapy. She did not complain of dry mouth or eyes. The laboratory findings showed high inflammation markers, rheumatoid factor 128 IU, Waaler-Rose 256 IU, anti nuclear antibody (ANA) 1/640, SSA (anti-Sjogren antigen A) and SSB (anti-Sjogren antigen B) positive and hypergammaglobulinemia. The Schirmer’s test resulted pathologic, the ultrasonography images and biopsy of salivar glands and minor salivary glands revealed focal periductal lymphocytic infiltrate and sialoduct ectasia class IV of juvenile Sjogren syndrome. The second case report describes a 7-year-old boy with enlargement of both parotid glands and fever which occurred twice a month, treated with antibiotics and adenotonsillectomy. In his family, his maternal aunt suffered from Sjogren syndrome and his mother was under investigation for suspected Sjogren syndrome. Under our observation the child showed rheumatoid factor 37 IU, ANA 1/1280, SSA and SSB positive. He didn’t complain of dry mouth or eyes but the eye examination showed signs of keratoconjuctivitis sicca. The ultrasonography images of salivary glands and parotids revealed chronic inflammation. Juvenile Sjogren syndrome is uncommon in children. Laboratory findings may be similar to those found in adults and it may be important to consider also familiar history and other clinical manifestations, which might be different from the adult form.

Significance of B cells and B cell clonality in Sjögren's syndrome

Sjogren’s syndrome (SS) is a chronic autoimmune disease in which the exocrine glands become sites of intense immunologic activity, leading to tissue damage that is manifested as mucosal dryness (1). This disorder can occur either alone, as primary SS, or on a background of another connective tissue disease, such as rheumatoid arthritis (RA), systemic sclerosis (SSc; scleroderma), or systemic lupus erythematosus (SLE), as secondary SS. One theory of the disease immunopathogenesis proposes that the syndrome is initiated by epitheliitis and is sustained by the ensuing influx of lymphocytes (2). Hence, the disease was referred to by those investigators as autoimmune epitheliitis. All affected organs, especially the salivary glands, exhibit a lymphoproliferative sialadenitis. Lymphoproliferative sialadenitis in SS is associated with lymphocyte infiltration, epithelial cell proliferation, and apoptosis (3). Compared with healthy individuals, patients with SS are at greater risk of developing non-Hodgkin’s lymphoma (4). Lymphocytes are therefore central to the pathophysiology of this autoimmune condition. However, there is controversy about which set of lymphocytes directs the immunopathologic process. Examination of the available evidence at a glance suggests that T lymphocytes play the principal role in the immunopathogenesis of these diseases. This proposition is based on the numerical predominance of T lymphocytes in the cellular composition of the inflamed tissues and on the restriction of the T cell receptor (5). One potential contradiction of this proposition, however, is that if the T lymphocytes were indeed the principal driving cells, then no increases in monoclonal Ig and B cell lymphoma would be seen in primary SS. Therefore, because the numerical predominance of T lymphocytes is not consistent with the clonal expansion of B cells in SS patients, attention has recently focused on the possibility that B lymphocytes play the leading role. Furthermore, there is good evidence to indicate that B lymphocytes promote the immune responses to self and non-self antigens through antibody-dependent and antibodyindependent mechanisms (6). Accumulation of B cells in exocrine glands results in their clustering into aggregates (7). There is nonetheless evidence from phenotype analyses suggesting that these aggregates are benign (8). Such findings raise questions as to why lymphomas frequently develop on a background of polyclonal proliferation of B cells in patients with SS (9). The frequent leukemic transformation in these patients with primary SS was first noted by Bunim and Talal (10). Subsequent studies by these investigators indicated that the two B cell aberrations were associated (11). They went on further to show a whole range of benign-to-malignant B cell proliferations in patients with primary SS, but not in those with secondary SS (12). Lymphoma in these patients has thus changed from an all-or-nothing phenomenon to one of a continuous spectrum of disease. This concept fits in with, but does not explain, the high frequency of lymphoma in patients with primary SS. In this review, we venture into the area of the ambiguous relationship between primary SS and B cell lymphoma. This analysis is focused in part on highlighting the centrality of B lymphocytes to the pathogenesis of primary SS and on exploring the likely processes that underpin the polyclonality or monoclonality of B cells in the disease. Our paradigm does not exclude a key role of Supported by the Association Francaise du Gougerot-Sjogren et des Syndromes Secs, the French Ministry for Education and Research, and the Institut Francais pour la Recherche Odontologique. Pierre Youinou, MD, DSc, Valerie Devauchelle-Pensec, MD, PhD, Jacques-Olivier Pers, DDS, PhD: EA2216 Immunology and Pathology, IFR 148 ScInBioS, European University of Brittany, and Brest University Medical School Hospital, Brest, France. Address correspondence and reprint requests to Pierre Youinou, MD, DSc, Laboratory of Immunology, Brest University Medical School Hospital, BP824, F29609 Brest, France. E-mail: youinou@univbrest.fr. Submitted for publication March 19, 2010; accepted May 11, 2010.