Primary Sjögren's Syndrome Patients Research Articles

IL‐10 Promoter −1082 Polymorphism is Associated with Elevated IL‐10 Levels in Control Subjects but Does not Explain Elevated Plasma IL‐10 Observed in Sjögren's Syndrome in a Hungarian Cohort

The aim of this study was to investigate the frequency of the -1082 polymorphism of the interleukin-10 (IL-10) gene and the soluble IL-10 levels in Hungarian primary Sjögren's syndrome (SS) patients. Ninety-nine SS patients and 135 healthy volunteers were examined. Samples were analysed by the PCR restriction fragment length polymorphism method, and IL-10 plasma levels were assessed by a commercial enzyme-linked immunosorbent assay. IL-10 plasma levels were higher in the primary SS patients (36.4 +/- 57.5 pg/ml, n = 99) compared with the healthy subjects (9.9 +/- 20.3 pg/ml, n = 135, P = 10(-6)). The elevated IL-10 phenotype of SS patients was not associated with increased G allele frequency as reported earlier, while in the control group, we found higher IL-10 levels among the subjects who were carriers of the GG genotype (17.7 +/- 23.2 pg/ml) as compared with the other two genotype carriers (AA 8.98 +/- 16.5 and GA 8.5 +/- 21.1 pg/ml, P = 0.01). Our data do not support previous observations indicating an association between deregulated IL-10 secretion in SS and higher G allele frequency. However, the results clearly demonstrate that GG homozygosity is associated with elevated IL-10 levels in apparently healthy subjects, but this cannot account for the IL-10-related specific disease features observed in SS. Thus, other genetic factors contribute to the clinical spectrum of this heterogeneous disease at least in the Hungarian population.

Lymphocytic Infiltration and Enlargement of the Lacrimal Glands: A New Subtype of Primary Sjögren’s Syndrome?

<h3>Purpose</h3> To review the clinical, radiologic, serologic, histopathologic, immunohistochemical, and molecular genetic features of patients having Sjögren's syndrome (SS) with lacrimal gland enlargement. <h3>Design</h3> Retrospective case series review. <h3>Participants</h3> Fourteen patients histopathologically diagnosed with SS with lacrimal enlargement. Twenty-three age- and gender-matched controls were used for comparison on radiologic analysis. <h3>Methods</h3> Clinical and serologic data were determined directly or by chart review. Computed tomography images from patients were compared with those from the control group. Histopathologic sections were reviewed and graded using the Chisholm-Mason scale, and quantitative immunohistochemical analysis was applied. <h3>Main Outcome Measures</h3> Clinically, patients were assessed for age, gender, onset, symptoms and signs, systemic features, treatment, and outcome. Existing histologic specimens were reviewed according to the Chisholm-Mason scale, and then the percentages of plasma cells containing immunoglobulin (Ig) A, IgG, and IgM were determined. Imaging was assessed for lacrimal gland thickness, prolapse, density, and margin contour; extraocular muscle size; orbital tissue displacement; and proptosis. <h3>Results</h3> Clinical and histopathological data fulfilled the revised American-European criteria for primary SS in 79% of patients. Compared with other large series of primary SS patients, similarities were found with age, xerophthalmia, parotidomegaly, and articular involvement. Differences included a lower incidence of autoantibodies, xerostomia, and extraglandular features and a higher male-to-female ratio. In almost all patients (93%), the percentage of plasma cells positive for IgA was less than 70%, consistent with SS. Compared with controls, the lacrimal glands were enlarged significantly (<i>P</i><0.0001) and prolapsed (<i>P</i><0.001). Involved glands had blurred margins (<i>P</i><0.007), caused displacement of adjacent tissues (<i>P</i> = 0.03), and were associated with hyperdense fat (<i>P</i> = 0.007). Lymphocytic infiltration of orbital fat was present in all patients for whom fat biopsy results were available. Three patients had monoclonal infiltrates, and 1 patient experienced subsequent extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type, 4 years after presentation. <h3>Conclusions</h3> The criteria used to diagnose primary SS are controversial, but both diagnostic and quantitative immunohistochemical criteria suggest that these patients, with lacrimal gland enlargement resulting from lymphocytic infiltration, represent a new subtype of primary SS. This is clinically important in view of the increased risk of lymphoma associated with SS, compared with idiopathic nonspecific lacrimal inflammation.

Detection of apoptosis-specific autoantibodies directed against granzyme B-induced cleavage fragments of the SS-B (La) autoantigen in sera from patients with primary Sjögren's syndrome

The objective of this study was to detect autoantibodies against granzyme B cleavage products in sera from patients with primary Sjögren's syndrome (SS). Cell lysates derived from human salivary gland (HSG) cell lines were incubated with granzyme B. The susceptibility to the generation of cleavage fragments of SS autoantigens was assayed by immunoblotting using sera from 57 primary SS patients, 17 primary SS patients with malignant lymphoma (ML), 28 systemic lupus erythematosus (SLE) patients, and 20 healthy controls. A 27 kD protein was recognized by serum autoantibodies in 8 (14.0%) of 57 primary SS patients, 5 (29.4%) of 17 SS patients with ML, 2 (7.1%) of 28 SLE patients, but not in 20 normal subjects. This protein was recognized by anti-SSB (La) monoclonal antibodies. Granzyme B-treated recombinant La protein was also shown to migrate as a discrete 27 kD protein by SDS PAGE. Blocking studies demonstrated the existence of an apoptosis-specific B cell epitope present in sera from 2 of 8 primary SS patients and in 2 of 5 primary SS patients with ML which recognized the 27 kD protein. Granzyme B-induced La fragments are generated during cytotoxicity in vitro. This is the first report describing autoantibodies in sera from primary SS patients that specifically recognize fragments of the La protein that are produced by the granzyme B protease.

Endothelıal dysfunctıon ın patıents wıth prımary Sjögren’s syndrome

The aim of this study was to determine the endothelial function in patients with primary Sjögren's syndrome (SS). We also aimed to determine whether endothelial (dys)function correlates with extraglandular manifestations, specific autoantibodies and the severity of salivary gland involvement of SS. Endothelium-dependent vasodilation and endothelium-independent vasodilation of the brachial artery were assessed by a high-resolution ultrasound on 25 patients with primary SS and on 29 healthy controls. Patients with primary SS had significantly less mean endothelium-dependent vasodilation than did controls (3.0 +/- 0.4% vs 4.2 +/- 0.3%; p = 0.012). Endothelium-independent vasodilation induced by sublingual glycerol trinitrate was not different between the two groups (12.9 +/- 1.4% vs 14.1 +/- 1.2%; p = 0.86). We concluded that endothelium-dependent vasodilation was impaired in primary SS patients, in particular those presenting with Raynaud's phenomenon, when compared with the healthy controls and this impairment was not associated with the presence of RF, ANA, anti-Ro/SS-A, anti-La/SS-B and with the other extraglandular manifestations of the disease.

Gene expression profiling of minor salivary glands clearly distinguishes primary Sjögren's syndrome patients from healthy control subjects

To identify gene expression signatures in minor salivary glands (MSGs) from patients with primary Sjogren's syndrome (SS). A 16K complementary DNA microarray was used to generate gene expression profiles in MSGs obtained from 10 patients with primary SS and 10 control subjects. The data were analyzed by 2 different strategies, one strict primary analysis and one subanalysis that allowed for inclusion of genes with no signal in more than 3 samples from each group. The results were validated by quantitative reverse transcriptase-polymerase chain reaction techniques. We found a distinct difference in gene expression levels in MSGs, enabling a simple class prediction method to correctly classify 19 of the 20 samples as either patient or control, based on the top 5 differentially expressed genes. The 50 most differentially expressed genes in the primary SS group compared with the control group were all up-regulated, and a clear pattern of genes involved in chronic inflammation was found. CXCL13 and CD3D were expressed in >/=90% of primary SS patients and in </=10% of the controls. Lymphotoxin beta, as well as a number of major histocompatibility complex genes, cytokines, and lymphocyte activation factors, manifested its role in the pathogenesis of SS. Numerous type I interferon genes related to virus infection were found among the top 200 genes, with increased expression in primary SS. Interestingly, the expression of carbonic anhydrase II, which is essential in saliva production and secretion, and the apoptosis regulator Bcl-2-like 2 were down-regulated in primary SS patients. We have identified distinct gene expression profiles in MSGs from patients with primary SS that provide new knowledge about groups of genes that are up-regulated or down-regulated during disease, constituting an excellent platform for forthcoming functional studies.

Diagnostic Potential of Tear Proteomic Patterns in Sjögren's Syndrome

Histological and functional changes of the lacrimal gland might be reflected in proteomic patterns in tear fluids. In this study, we carried out a determination of the disease biomarkers in tear fluid for Sjögren's syndrome (SS) and a performance of noninvasive diagnostic test based on the proteomic patterns. Thirty-one SS patients and 57 control subjects were enrolled to this study. Their details were 23 cases with primary SS, 8 with secondary SS, 14 with dry eyes, 22 with miscellaneous ocular diseases, and 21 of healthy volunteers. Protein profiling in tear fluids was identified by surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Multiple protein changes were reproducibly detected in the primary SS group, including 10 potential novel biomarkers. Seven of the biomarkers (2094, 2743, 14191, 14702, 16429, 17453, 17792 m/z) were down-regulated and 3 biomarkers (3483, 4972, 10860 m/z) were up-regulated in primary SS group, comparing to the protein profiles of control subjects. When cutoff value of SS down-score was set less than 0.5, this result yielded 87% sensitivity and 100% specificity. The positive predictive value for this sample set was 100%. There was a significant inverse correlation between SS down-scores and epithelial damages of the ocular surface in primary SS patients. These findings support the potential of proteomic pattern technology in tear fluids as the noninvasive diagnostic test for primary SS.

Circulating Monoclonal Immunoglobulins in Sjögren Syndrome

We conducted the current study to analyze the prevalence and clinical significance of circulating monoclonal immunoglobulins in patients with Sjögren syndrome (SS), focusing on the association with extraglandular features, immunologic markers, hematologic neoplasia, and hepatitis C virus (HCV) infection. We performed serum immunoelectrophoresis in 200 patients with primary SS and 37 patients with HCV-related SS. All patients fulfilled 4 or more of the 1993 European classification criteria for SS.Of the 200 patients with primary SS, 35 (18%) presented circulating monoclonal immunoglobulins. The monoclonal bands identified were 20 IgG (13 kappa, 7 lambda), 10 IgM (5 kappa, 5 lambda), 2 IgAkappa, and 3 free circulating light chains. Of the 37 SS-HCV patients, 16 (43%) had circulating monoclonal immunoglobulins. The monoclonal bands identified were 10 IgMkappa, 5 IgGlambda, and 1 free light lambda chain. Compared with primary SS patients, SS-HCV patients presented a higher frequency of monoclonal immunoglobulins (43% vs 18%, p = 0.001), with monoclonal IgMkappa being the most frequent monoclonal band. Six (12%) of the 51 SS patients with circulating monoclonal immunoglobulins presented hematologic neoplasia, compared with 3 (1.6%) of those without monoclonal immunoglobulins (p = 0.004; odds ratio = 8.13; 95% confidence intervals, 1.64-51.54). In 2 of the 6 patients with monoclonal immunoglobulins and lymphoproliferative disorders, a change of the monoclonal component was detected in previous immunoelectrophoresis determinations before the development of hematologic neoplasia. Circulating monoclonal immunoglobulins were detected in nearly 20% of patients with primary SS, with monoclonal IgG being the most frequent type of immunoglobulin detected. In SS-HCV patients, the prevalence of monoclonal immunoglobulins was higher (43%), with monoclonal IgM being the most frequent type found. SS-HCV patients presented a more restrictive monoclonal expression (limited to either monoclonal IgMkappa or monoclonal IgGlambda) than primary SS patients, who showed all types of heavy and light chains.

Oral health condition and saliva flow in southern Chinese with Sjögren’s syndrome

To investigate the oral health condition and saliva flow of southern Chinese patients with Sjögren's syndrome (SS). 51 SS patients (26 primary and 25 secondary cases) and 29 controls took part in this cross-sectional study. Stimulated whole and parotid saliva flow rates, pH, and buffer capacity, and xerostomia, oral mucosal lesions, oral hygiene status, dental and periodontal conditions, prosthetic status were assessed and compared between groups. Stimulated whole saliva (SWS) flow was reduced in primary and secondary SS cases (p<0.001), pH and buffer capacity were also reduced in the primary SS group (p<0.05). SS patients had a greater prevalence of xerostomia than controls (p<0.001). Primary SS patients had a higher mean DMFT, more missing teeth, and more prostheses than secondary SS cases and controls (p<0.05). SWS flow correlated negatively with the number of filled teeth in both SS groups (p<0.05) and the number of decayed teeth in the primary SS group (p<0.05). Despite good oral hygiene and regular dental check-ups, the oral health of southern Chinese with primary SS was significantly compromised compared with secondary SS cases and controls, most probably due to the combined effect of impaired salivary gland function and poorer saliva buffer capacity.

Measurement of fatigue and discomfort in primary Sjögren's syndrome using a new questionnaire tool

Fatigue is a prominent symptom in primary Sjögren's syndrome (PSS). We set out to compare existing instruments and a new tool for measuring fatigue and general discomfort in PSS, with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and healthy controls. Groups of female Caucasian PSS patients completed a new questionnaire developed from PSS patients' own vocabulary, as well as the SF-36, WHOQOL-BREF and HAD scales. For comparison, the questionnaire was also completed by groups of SLE and RA patients and healthy controls. Each disease group differed significantly from healthy controls on each facet of fatigue and general discomfort in the new tool. Somatic fatigue was worst in RA, while mental fatigue was worst in PSS and SLE. The facets of somatic fatigue and discomfort in the new tool correlated well with comparable domains in existing scales. Fatigue in PSS can be measured using this new Sjögren's-based psychometric instrument. The new questionnaire tool was more sensitive than the SF-36, WHOQOL-BREF and HAD at distinguishing the three rheumatic disorders from controls.

Psychiatric and central nervous system involvement in Sjogren's syndrome

To study psychiatric features and the manifestations of central nervous system involvement in Chinese patients with primary Sjogren's syndrome (PSS). The Minnesota Multiphasic Personality Inventory (MMPI) was used to study 27 PSS female patients and 57 healthy women. The results from two groups were compared. Ten SS patients were evaluated by electroencephalography (EEG), transcranial doppler ultrasound (TCD) and magnetic resonance imaging (MRI). Of 27 patients tested, the three highest clinical mean scales included Hypochondriasis (Hs), Hysteria (Hy), Psychasthenia (Pt) were found. When PSS group was compared with normal control, T scores of SS patients were significantly higher than the healthy women in Hs, Hy. Abnormal EEG was found in 3 of 9 PSS patients. TCD was abnormal in 5 of 9 patients. MRI in 1 patient showed abnormality. This study shows that the personality of PSS patients is abnormal, the features are neuroticism. Central nervous system was markedly involved in Chinese patients with PSS, including abnormal EEG and TCD. The changes of central nervous system may be related to abnormalities of psychiatric changes.

Manometric assessment of esophageal motility in patients with primary Sjögren's syndrome.

The aim of this study was to assess the esophageal motility by manometry in patients with primary Sjögren's syndrome. Esophageal manometry was carried out in 40 patients with primary Sjögren's syndrome (SS), 15 with rheumatoid arthritis (RA), 15 with RA and secondary SS, and 21 healthy volunteers. We found that the mean lower esophageal sphincter (LES) pressures measured by station pull-through and rapid pull-through techniques were significantly higher in primary SS patients than with healthy controls and RA patients with or without SS (P<0.05). Our study did not show any major differences when comparing the three patient groups (P>0.05). However, peristaltic contraction velocity was lower and peristaltic contraction duration significantly higher at the middle and lower thirds of the esophagus in primary SS patients than in healthy controls (P<0.05). The results of our study support the view that various esophageal motility disorders can be found in patients with primary SS which could be related to an increase in LES pressure. We also found no correlation of the esophageal abnormalities with other factors studied, suggesting that the cause of dysphagia is multifactorial in nature.

Physical capacity in women with primary Sjögren's syndrome: A controlled study

To examine physical capacity (aerobic capacity, joint mobility, muscle function, and standing balance) in women with primary Sjögren's syndrome (primary SS) and to examine the correlation of aerobic capacity with fatigue, functional disability, and mental aspects (anxiety and depression). Fifty-one women who fulfilled the European Community criteria for primary SS and who had anti-SSA/SSB antibodies or a positive lip biopsy were compared with 51 age-matched controls. Physical capacity, fatigue, functional disability, anxiety, and depression were investigated by means of questionnaires and clinical examinations. The women with primary SS had significantly decreased aerobic capacity (VO(2max) = 28.7 versus 32.4 ml/kg/minute; P = 0.013), shoulder mobility (58 versus 59 scale points; P = 0.003), grip strength (214 versus 259 N; P = 0.000), isokinetic strength of the knee flexors (51 versus 56 Nm; P = 0.049), endurance of the knee flexors (620 versus 712 J; P = 0.008), and standing balance (25 versus 28 seconds; P = 0.006) when compared with the reference group. For the primary SS patients, greater effort was needed to carry out the test of aerobic capacity, and they experienced more pain during the shoulder mobility test. Aerobic capacity correlated with the fatigue experienced (r = -0.33, P = 0.022) but not with functional disability or mental aspects. The results indicate that women with primary SS have decreased physical capacity, which may be related to the experience of fatigue.

Salivary and serum β2-microglobulin and gamma-glutamyl-transferase in patients with primary Sjögren syndrome and Sjögren syndrome secondary to systemic lupus erythematosus

Background: Sialochemistry has been proposed as a simple and useful tool for the diagnosis of Sjögren syndrome (SS). Although many changes have been detected in several constituents of saliva from patients with SS, none are individually sensitive or specific enough for diagnosing SS. The aim of this study was to assess the value of the combined determination of β2-microglobulin (β2m) and gamma-glutamyl-transferase (GGT) activity in serum and saliva as a diagnostic instrument for differentiating primary and secondary [to systemic lupus erythematosus (SLE)] SS patients from normal subjects. Methods: Nineteen primary SS (pSS) patients, 15 patients with SS secondary to SLE, and 25 SLE patients without SS were studied. Thirty healthy subjects were included in the study as control group. Results: By means of a mathematical model, (a) 84.1%, (b) 85.7%, and (c) 87.0% of patients were correctly classified as SS or normal when (a) salivary β2m and GGT values, (b) serum β2m and salivary GGT values, and (c) salivary β2m and GGT along with serum β2m values, respectively, were considered. To differentiate between pSS and sSS by means of the mathematical model, the combination of serum β2m and salivary GGT values achieved that 81.8% of the patients were correctly classified. Conclusion: Since sialochemistry is an easy, safe and reliable test, the combined determination of β2m and GGT in saliva and serum was useful for differentiating SS patients from normal subjects, but not excessively good for differentiating pSS from sSS patients.

Paraneoplastic antineuronal antibodies in patients with systemic autoimmune diseases.

Sera from 71 patients with primary Sjögren's syndrome (PSS) and from 102 patients with systemic lupus erythematosus (SLE) were tested by immuno-dot blotting against HuD, Ri, Yo and amphiphysin recombinant proteins. For Ri, Yo and amphiphysin antigens, no immunoreactivity was found in the 173 sera tested. One PSS patient with a clinical picture of subacute sensory neuronopathy had high titers of anti-Hu antibodies. An extensive search for an underlying tumor was initially negative but a small cell lung cancer was eventually discovered three years later. Another patient with SLE and a clinical picture of demyelinating polyradiculoneuropathy had anti-Hu antibodies. Repeated search for an underlying tumor remains negative after five years follow-up in this young non-smoking patient. In addition, the neuropathy progressively improved and the anti-Hu antibodies titer slowly decreased from 1:8000 to 1:2000, making the diagnosis of paraneoplastic syndrome unlikely in this patient. This study indicates that the detection of anti-Hu antibodies in patients with known symptomatic systemic autoimmune diseases such as PSS or SLE should induce the same work-up than the detection of these antibodies in the absence of other immune diseases, i.e. repeated search for occult cancer during several years. As illustrated by our first patient, this strategy may be fruitful. Nevertheless, the clinician should know that anti-Hu antibodies may exceptionally (0.6% in this series) occur in systemic autoimmune disorders with neurological complications, in the absence of an underlying neoplastic disease.

The assessment of fatigue in primary Sjögren's syndrome

Objective. Disabling fatigue is a prominent feature of primary Sjögren's syndrome (PSS). We evaluated a number of questionnaires for their ability to discriminate fatigue in PSS from that in other rheumatic disorders and healthy controls.Methods. 33 female caucasian patients with PSS, 45 with rheumatoid arthritis (RA), 16 with systemic lupus erythematosus (SLE) and 30 controls completed self‐administered questionnaires including; Visual Analogue Scales (VAS), the Chalder Fatigue Scale (CFS), the Nottingham Health Profile (NHP) and the Medical Outcomes Short Form 36 Questionnaire (SF‐36).Results. All patient groups scored significantly worse than controls on the ‘Energy’ dimension of the NHP, the fatigue VAS and the ‘Vitality’ domain of the SF‐36. No significant differences were observed between PSS patients and controls using the CFS.Conclusions. The NHP, VAS and SF‐36 are useful in identifying fatigue in these rheumatic disorders. Further work is required to identify the characteristic features of fatigue in these conditions.

Photoprovocation test and immunohistochemical analysis of inducible nitric oxide synthase expression in patients with Sjögren's syndrome associated with photosensitivity.

Annular erythema (AE) in Sjögren's syndrome (SS) usually develops on areas of sun-exposed skin and is exacerbated during summer. To evaluate photosensitivity in SS and to investigate the involvement of ultraviolet (UV) radiation in the development of AE in SS. Phototesting with UVA and UVB was performed on 14 SS patients, including 10 with primary SS. Clinical and histological features as well as expression of inducible nitric oxide synthase (iNOS) in the evoked skin lesions were compared with those of lupus erythematosus (LE). Eleven SS patients had a history of photosensitive AE (n = 4), papules (n = 3) or other types (n = 4) of lesions on their sun-exposed skin that were induced or aggravated by sunlight exposure. Phototesting induced a prolonged erythematous response (n = 8), infiltrated erythema (IE) (n = 4) and/or papules (n = 3) in 11 of 14 SS patients, including one with primary SS without a history of photosensitivity. Histologically, the induced IE and papules showed coat-sleeve-like or sparse perivascular infiltration of lymphocytes similar to that in primary skin lesions of AE in SS. No epidermal changes characteristic for LE were found except for partial and mild liquefaction degeneration in three cases. In contrast, two cases were indistinguishable from the papular type of polymorphic light eruption in several aspects, including their primary skin lesions and early response to a photoprovocation test. Immunohistochemistry revealed diffuse expression of iNOS throughout the epidermis, which is characteristic for LE, in the three SS patients with minimal liquefaction degeneration, while the remaining seven SS patients examined exhibited no iNOS staining or a normal expression pattern. Our results indicate that photosensitivity exists in certain primary SS patients, and that UV is critical to the development of AE in SS, probably through a pathological mechanism distinct from that in LE.

Subcellular redistribution and surface exposure of the Ro52, Ro60 and La48 autoantigens during apoptosis in human ductal epithelial cells: a possible mechanism in the pathogenesis of Sjögren's syndrome.

The Ro52, Ro60 and La48 autoantigens are associated with Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE). The mechanisms behind tolerance breakdown of these self-peptides remain unclear; however, apoptosis has been proposed to cause their presentation to the immune system. We have examined the localization of transiently expressed enhanced green fluorescent protein (EGFP)-tagged Ro52, Ro60 and La48 autoantigens in a human salivary gland (HSG) cell line by laser confocal microscopy under normal growth conditions and during apoptosis. Surface exposure of Ro52, Ro60 and La48 was demonstrated on nonfixed apoptotic cells with monoclonal antibodies (MoAbs) or with primary SS patient antisera. Laser scanning cytometry determined the apoptotic frequency. EGFP alone was studied as control. We found that Ro52 mainly is cytoplasmic, Ro60 both nuclear and cytoplasmic, while La48 only resides in the nucleus under normal conditions. During early apoptosis, La48 is dramatically redistributed to the cytoplasm, while the localization of Ro52 and Ro60 is maintained. All three autoantigens filled apoptotic blebs and covered TUNEL (terminal-deoxynucleotidyl-transferase-mediated dUTP-digoxigenin nick end labelling)-positive apoptotic bodies. Identical results were obtained in COS-7 cells. We have developed a transfection system to study the intracellular localization of the three autoantigens Ro52, Ro60 and La48, without antibody detection. During apoptosis, there is an intracellular redistribution of endogenous and EGFP-tagged Ro52, Ro60 and La48, leading to surface exposure. These findings may indicate a role for apoptosis in the induction and facilitation of humoral responses to Ro52, Ro60 and La48 in the autoimmune exocrinopathy of SS.

Th1/Th2 cytokine imbalance in patients with Sjögren syndrome secondary to hepatitis C virus infection

Objective: To investigate if the serum immunologic profile, as delineated by serum circulating levels of Th1/Th2 cytokines and autoantibodies, is different in patients with Sjögren syndrome (SS) with and without hepatitis C virus (HCV) infection. Methods: This study included 20 patients with HCV-related SS and 47 consecutive patients with primary SS. All fulfilled 4 or more of the modified 1996 European criteria for SS. Serum levels of interleukin (IL)-2 (pg/mL), srIL-2 (pM), tumor necrosis factor (TNF)-α (pg/mL), IL-6 (pg/mL), and IL-10 (pg/mL) were determined using enzyme immunoassay. We also analyzed the following immunologic tests: anti-nuclear antibodies (ANA), anti-mitochondrial antibodies (AMA), anti–parietal cell antibodies (PCA), anti–smooth muscle antibodies (SMA), anti–liver-kidney microsome antibodies type-1 (LKM-1), anti–Ro/SS-A, anti–La/SS-B, rheumatoid factor (RF), complement factors (C3 and C4), and cryoglobulins. Results: Of the 20 patients with HCV-related SS, 18 were women and 2 men (mean age, 66 years). Patients with HCV-related SS had a different cytokine profile compared with patients with primary SS, with higher circulating levels of IL-6 (73.6 v 33.0 pg/mL, P =.045), IL-10 (6.7 v 3.1 pg/mL, P =.01), srIL-2 (124.6 v 72.7 pM, P =.001), and TNF-α (59.8 v 31.7 pg/mL, P =.003). The main immunologic features were ANA, detected in 75% of patients, RF in 63%, cryoglobulinemia in 50%, hypocomplementemia in 40%, SMA in 30%, PCA in 25%, anti–Ro/SS-A in 25%, AMA in 20% and anti–La/SS-B in 16%. When compared with primary SS patients, those with HCV-related SS had a higher prevalence of AMA (20% v 2%, P =.025), hypocomplementemia (40% v 11%, P =.015), and cryoglobulinemia (50% v 12%, P =.003). Conclusion: Although chronic HCV infection may mimic the main clinical, histologic and immunologic features of primary SS, patients with HCV-related SS showed some differentiated characteristics, including a predominant Th2 pattern and a higher frequency of cryoglobulinemia and hypocomplementemia (features closely related to HCV). This suggests that the SS observed in some HCV patients should be interpreted as one of the extrahepatic manifestations of chronic HCV infection. Semin Arthritis Rheum 32:56-63. Copyright 2002, Elsevier Science (USA). All rights reserved.

Role of Salivary IgA in the Pathogenesis of Sjögren Syndrome

Saliva IgA autoantibodies against M 3 muscarinic acetylcholine receptors (mAChRs) could be a new marker for the diagnosis for Sjögren syndrome (SS) dry mouth. Saliva IgA from dry mouth primary SS (pSS) or secondary SS patients tested by ELISA recognized membrane parotid gland acinar cell antigens and the synthetic 25-mer peptide corresponding to the second extracellular loop of human M 3 mAChRs. Moreover, the IgA fraction was able to inhibit the [ 3H]QNB binding to parotid acinar membrane mAChRs. In addition, the IgA prevented carbachol stimulation of protein secretion by the parotid gland. As controls, IgA and saliva from women without dry mouth and from normal control subjects gave negative results on ELISA, binding, and biological assays, thus demonstrating the specificity of the reaction. IgA autoantibodies against mAChR may be considered among the immunoglobulin factors implicated in the pathophysiology of the development of pSS dry mouth and could be a new marker for differentiating SS dry mouth from non-SS dry mouth.

Fatigue in daily life in patients with primary Sjögren's syndrome and systemic lupus erythematosus.

Fatigue is a well-recognized complaint with major impact on daily life in primary Sjögren's syndrome (PSS) and systemic lupus erythematosus (SLE). Previous research has not taken into account several crucial aspects of fatigue. This study examined various aspects of fatigue in the daily life of patients with PSS and SLE and in healthy controls. We compared age-adjusted, repeated measurements of fatigue across the day of female patients with SLE (n = 20, mean age 43.4 +/- 11.3), with PSS (n = 28, mean age 53.7 +/- 13.9) and healthy participants (n = 30, mean age 50.5 +/- 13.4). General and physical fatigue was significantly higher in patients than in healthy participants. Groups did not differ with respect to average levels of reduced motivation or mental fatigue. Both general and physical fatigue and reduced activity varied significantly during the day. Adjusting for depressive symptoms, groups showed significantly different time courses during the day. In healthy participants and patients with SLE, fatigue first decreased and then increased, whereas a rather opposite course-at least for the first part of the day-was observed in patients with PSS. Using an ecologically valid assessment method, we demonstrated substantially higher levels of daily fatigue in SLE and PSS patients as compared to healthy participants, thereby jeopardizing these patients' quality of life. The effect of disease on variations in fatigue over the day should be the subject of further inquiry, especially as it might clarify underlying mechanisms.