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ID PMID Title PublicationDate abstract
16980211 New cytokine targets in inflammatory rheumatic diseases. 2006 Oct With the advent of biological therapies, considerable advances have been achieved in the treatment of inflammatory arthritis. These have arisen primarily from studies elucidating mechanisms of pathophysiology and are best exemplified in the wide use of tumour necrosis factor (TNF) blockade in several rheumatic diseases. The identification of additional pro-inflammatory factors in rheumatic diseases and an understanding of their effector function, now offers major possibilities for the generation of novel therapeutics. To address unmet clinical need, such interventions will ideally fulfil several of the following criteria: (1) control of inflammation, (2) modulation of underlying immune dysfunction - promoting the re-establishment of immune tolerance, (3) protection of targeted tissues such as bone and cartilage - this should encompass promoting healing of previously damaged tissues, (4) preservation of host immune capability - to avoid profound immune suppression and (5) amelioration of co-morbidity associated with underlying inflammatory arthritis. This short review will consider those novel cytokine activities that represent optimal utility as therapeutic targets. Since we wish to reflect the current predominant research effort, we will focus primarily on rheumatoid arthritis (RA) based studies.
18390896 Social functioning and facial expression recognition in survivors of pediatric brain tumor 2008 Nov OBJECTIVE: To assess social functioning and facial expression recognition skill in survivors of pediatric brain tumors (BT) as compared to children with juvenile rheumatoid arthritis (JRA). METHODS: The social functioning of 51 survivors of BT and 31 children with JRA was assessed using a facial expression recognition task, questionnaire ratings of social functioning, and an IQ screener. RESULTS: After controlling for estimated IQ, survivors of BT made significantly more errors interpreting adult facial expressions as compared to children with JRA. Additionally, history of therapy and diagnosis age predicted performance on the child portion of the facial recognition task. Finally, survivors of BT demonstrated significantly impaired social functioning across multiple measures when compared to children with JRA. CONCLUSIONS: Survivors of pediatric BT showed significant deficits in social functioning as compared to an illness comparison group. Errors in facial expression recognition represent another method for evaluating deficits that contribute to social outcomes.
16889732 [Arthroscopic assisted diagnosis and treatment of knee extension limitation]. 2006 Jun 15 OBJECTIVE: To figure out the incidence and etiology of knee extension limitation and then to find out the proper methods of arthroscopic assisted diagnosis and treatment. METHODS: We reviewed 303 cases of arthroscopic assisted operation from January to October 2003, 95 cases of which suffered from knee extension limitation before operation, including 54 male and 41female and the mean age was 36.2 years old. The direct reasons of knee extension limitation were identified by routine arthroscopic examination and operations were carried out according to results of the examination. RESULTS: Incidence of knee extension limitation in this group of patients was 31.4%. Trauma, mainly meniscus and ligament injury accounted for 67.4%, which was the most common reason of knee extension limitation. Acute or chronic arthritis like degenerative arthritis, non-specific synovitis, synovial chondromatosis, rheumatoid arthritis, pigmented villonodular synovitis, gouty arthritis and acute pyogenic arthritis formed another common reason. The follow-up period ranged from 3 to 20 months, average 13.3 months. 82 cases gained full extension immediately after operation, 9 cases gained full extension after 3 weeks rehabilitation post-operation, 4 cases did not gain full extension 1 year after operation, recurrence was observed in 4 cases. CONCLUSIONS: Arthroscopy is the best method for diagnosis of knee extension limitation at present. Satisfactory results can be expected after early arthroscopic assisted treatment.
16038012 A novel approach for gene therapy: engraftment of fibroblasts containing the artificial ch 2006 Jan BACKGROUND: Rheumatoid arthritis is characterized by inflammation of the synovial tissue. High systemic doses are necessary to achieve therapeutic levels of anti-rheumatic drugs in the joints. Gene transfer might provide a more efficient delivery system for genes encoding therapeutic proteins. METHODS: The artificial chromosome expression system (ACE System) is a new non-integrating, non-viral gene expression system which functions like a natural chromosome. This technology offers advantages over current expression systems because it allows stable and predictable expression of proteins encoded by single or multiple genes over long periods of time. We are developing ex vivo gene therapy using murine artificial chromosomes containing a reporter gene (LacZ and red fluorescent protein (RFP)) for local delivery of genes in rats with adjuvant arthritis (AA). RESULTS: The delivery of the intact ACE System into rat fibroblast-like synoviocytes (FLS) and rat skin fibroblasts (RSF) was detected within 24 to 48 h post-transfection. After growing cells under selection, clones expressing LacZ and RFP were identified. Furthermore, we investigated the feasibility of local delivery of a reporter gene to the joints of rats with AA by ex vivo gene therapy. This resulted in engraftment of the injected cells in the synovial tissue microarchitecture and expression of the reporter gene. CONCLUSIONS: This work demonstrates the potential feasibility of treating arthritis and other inflammatory diseases using fibroblasts containing the ACE System as a non-viral vector for gene therapy.
16879255 Arthritogenicity of collagen type II is increased by chlorination. 2006 Aug During inflammation, activated neutrophils, monocytes and macrophages produce and release myeloperoxidase (MPO). MPO converts hydrogen peroxide to hypochlorous acid, a highly reactive and oxidizing agent. Proteins subjected to hypochlorous acid become chlorinated. We analysed how chlorination of the cartilage antigen collagen type II (CII) affects its immunogenic and arthritogenic properties by studying immune responses to chlorinated CII in comparison to immune responses to CII and by studying the development of arthritis in rats immunized with CII-Cl. CII-Cl immunization of LEW.1AV1 rats caused a 100% incidence of arthritis with a mean maximum score of 9.2 (maximal score possible 16). The same dose of non-chlorinated CII did not induce arthritis at all. Rats immunized with CII-Cl developed high anti-CII-Cl IgG titres and also developed IgG antibodies recognizing the non-chlorinated form of CII. Analysis of cytokine mRNA expression in lymph nodes 10 days after immunzation revealed an increased expression of interferon (IFN)-gamma mRNA and interleukin (IL)-1beta mRNA in CII-Cl-immunized rats compared to CII-immunized rats. Thus, chlorination of CII increased its immunogenicity as well as its arthritogenicity. As neutrophils, monocytes and macrophages are abundant cells in arthritic joints of patients with rheumatoid arthritis, chlorination might be a mechanism by which immunoreactivity to CII is induced and by which chronic joint inflammation is supported.
16249085 Pyrazoloheteroaryls: novel p38alpha MAP kinase inhibiting scaffolds with oral activity. 2006 Jan 15 A test library with three novel p38alpha inhibitory scaffolds and a narrow set of substituents was prepared. Appropriate combination of substituent and scaffold generated potent p38alpha inhibitors, for example, pyrazolo[3,4-b]pyridine 9, pyrazolo[3,4-d]pyrimidine 18a and pyrazolo[3,4-b]pyrazine 23b with potent in vivo activity upon oral administration in animal models of rheumatoid arthritis.
18843953 [A clinical analysis of primary Sjögren's syndrome with anticentromere antibodies]. 2008 Apr OBJECTIVE: To investigate the clinical manifestations, immunological features and prognosis of primary Sjögren's syndrome (pSS) with anticentromere antibodies (ACA). METHODS: Sixty pSS patients with ACA in our hospital between 1985 and 2006 were screened retrospectively and compared with those without ACA. RESULTS: The mean age at the onset of pSS with ACA was higher than that of those without ACA [(48 +/- 11) yr vs (41 +/- 12) yr, P =0.000]. There was no difference in sex ratio, dry mouth, dry eyes and positive salivary gland biopsy between the two groups (P > 0.05). Compared with those without ACA, patients with ACA presented a higher prevalence of liver involvement (68.3% vs 37.0%, P = 0.000), while a lower prevalence of renal involvement (13.3% vs 30.9%, P = 0.009), neuropathy (1.7% vs 11.5%, P = 0.025) and hypergammaglobulinemia (20.8% vs 45.7%, P = 0.002). The difference was not significant between the two groups in Raynaud's phenomenon, articular involvement, myositis, hematologic involvement, lung involvement, and thyroiditis. While both groups showed the same prevalence of antinuclear antibody (ANA), the patterns of ANA-IF were different and the discrete speckled pattern was the most frequent in patients with ACA and occurred in 61.7%. Different from those without ACA, patients with ACA presented a lower prevalence of anti-SSA, anti-SSB, rheumatoid factor, and anti-U1RNP, while showed a higher prevalence of antimitochondrial antibodies (AMA) and AMA-M2. The most frequent cause of death was the complications associated with cirrhosis, notably bleeding varices (3/5 cases). CONCLUSION: Patients with ACA present a high risk of liver involvement. Because of the remarkable difference in the mean age of disease onset and also differences in systemic damage, immunological and antibody features, pSS with ACA may be a special subtype of pSS.
17881909 Management of ocular surface inflammation in Sjögren syndrome. 2007 Oct PURPOSE: To evaluate the clinical efficacy of anti-inflammatory therapy in the management of primary Sjögren syndrome. METHODS: Thirty-eight patients with primary Sjögren syndrome were included in this study. The diagnosis of Sjögren syndrome was made on the basis of the classification criteria of the American-European Consensus Group. Fluorescein staining score, rose-bengal staining score, Schirmer test score, tear film breakup time, and functional parameters including ocular surface disease index (OSDI) and visual analog scale (VAS) score were measured at the first visit. Anti-inflammatory therapy included topical corticosteroids, topical autologous serum, and topical cyclosporin A. The clinical efficacy of anti-inflammatory treatment was evaluated in terms of subjective symptoms and objective signs (including Schirmer-1 test, breakup time, rose-bengal score, and fluorescein score). RESULTS: Patients with Sjögren syndrome had higher rose-bengal scores than patients with non-Sjögren dry eye (P < 0.05). The OSDI score showed better correlation with fluorescein score than with VAS score. Subjective symptoms improved with anti-inflammatory treatment in 70% of patients with primary Sjögren syndrome. Anti-inflammatory treatment provided significant improvement in visual acuity and fluorescein score but did not affect Schirmer score, tear breakup time, or rose-bengal score. CONCLUSIONS: Anti-inflammatory therapy in primary Sjögren syndrome significantly improved subjective symptoms and objective ocular signs; however, we did not find evidence that anti-inflammatory treatment increases tear production in patients with Sjögren syndrome.
17345806 [Lacrimal proteins electrophoretic analysis--diagnostic method in secondary Sjogren syndro 2006 PURPOSE: We analysed and compared electrophoretic tear protein patterns of healthy subjects and patients with different autoimmune diseases associated with secondary Sjogren's syndrome. MATERIALS AND METHODS: Tears were collected using the Schirmer's method. Proteins were separated by sodium-dodecyl sulfate poliacrylamide gel electrophoresis. The lanes were stained by Coomassie blue and/or silver. RESULTS: Lactoferrin, albumin, lipocalin and lysozyme were found to be the main components being identified using molecular weight markers. CONCLUSIONS: Electrophoretic analysis of tear proteins patterns is a fast, reproducible and simple method which provides information about the possibility of lacrimal gland involvement in autoimmmune diseases.
17911478 A new orally bioavailable synthetic androstene inhibits collagen-induced arthritis in the 2007 Sep Dehydroepiandrosterone (DHEA) has attracted much interest because of its many antiaging, metabolic and immune-modulating effects in rodents. Synthetic derivatives, such as 5-androstene-16alpha-fluoro-17-one (HE2500) and certain natural metabolites also provide benefit in various animal models of autoimmune and metabolic diseases. But, like DHEA, low potency and low oral bioavailability suggested limited usefulness of these compounds in humans. We hypothesized that HE3286, a novel 17-ethynyl derivative would be orally bioavailable, more potent, and chemically more useful in man than its parent compound. We found that on a dose/mass basis, HE3286 demonstrated up to 25% oral bioavailability in mice. In the DBA mouse model of collagen-induced arthritis (CIA), animals receiving oral treatment with HE3286 (50 mg/kg), beginning at onset of disease, significantly decreased CIA peak scores and daily severity of arthritis scores. Benefit was associated with decreases in: (1) production of TNF-alpha, IL-6, and IL-17; and (2) decreases in joint inflammation, erosion, and synovial proliferation as judged by histological analysis. HE3286 was not found to be immune suppressive in any of the classical models tested, including mitogen-induced proliferation, delayed-type hypersensitivity, or mixed lymphocyte reaction. Instead, benefit was associated with increases in numbers and function of CD4+CD25+FOXp3+CD127- regulatory T cells (T reg). To our knowledge, this is probably the first study to report that an orally bioavailable synthetic analogue of DHEA can ameliorate ongoing disease in a CIA mouse model with relevance to rheumatoid arthritis (RA) and to correlate that finding with decreases in proinflammatory cytokines and increases in T reg cells. Hormones targeting T reg cells hold the intriguing potential to treat autoimmune, infectious, and neoplastic diseases.
17911637 Hepatocyte growth factor significantly suppresses collagen-induced arthritis in mice. 2007 Oct 15 Hepatocyte growth factor (HGF) plays an important role in angiogenesis, cell proliferation, antifibrosis, and antiapoptosis. Moreover, recent studies have highlighted the immunosuppressive effect of HGF in animal models of allogenic heart transplantation and autoimmune myocarditis and in studies in vitro as well. We also reported that HGF significantly suppresses dendritic cell function, thus down-regulating Ag-induced Th1-type and Th2-type immune responses in allergic airway inflammation. However, the immunosuppressive effect of HGF in many other situations has not been fully clarified. In the present study, using a mouse model of collagen-induced arthritis (CIA) and experiments in vitro, we examined the effect of HGF on autoimmune arthritis and then elucidated the mechanisms of action of HGF. To achieve sufficient delivery of HGF, we used biodegradable gelatin hydrogels as a carrier. HGF suppressed Ag-induced T cell priming by regulating the functions of dendritic cells in the Ag-sensitization phase with down-regulation of IL-10. In contrast, under continuous Ag stimulation HGF induced IL-10-producing immunocytes both in vivo and in vitro. Moreover, HGF potently inhibited the development of CIA with enhancing the Th2-type immune response. We also confirmed that HGF significantly suppressed the production of IL-17 by immunocytes. These results indicate that HGF suppresses the development of CIA through different ways at different phases. They also suggest that HGF could be an attractive tool for treating patients with rheumatoid arthritis.
17673151 T cells are involved in the development of arthritis induced by anti-type II collagen anti 2007 Oct T cells play an important role in initiating autoimmune responses and maintaining synovial inflammation in rheumatoid arthritis. Although, anti-type II collagen antibody-induced arthritis (CAIA) is generally believed to be a T cell- and B cell-independent model, the detailed pathogenesis of CAIA remains unclear. In the present study, to elucidate the contribution of T cells to the pathogenesis of CAIA, we evaluated the effects of CTLA4 Ig and cyclosporin (CsA). Arthritis was induced in mice by intravenous injection of anti-type II collagen antibody followed by intraperitoneal injection of lipopolysaccharide. CTLA4 Ig was intraperitoneally administered and CsA was subcutaneously administered; then the severity of arthritis was evaluated by scoring the edema and erythema of paws and by measuring hind paw thickness. Paw samples were collected 12 days after the antibody injection, and the mRNA expression levels were analyzed by real-time quantitative polymerase chain reaction. Administration of CTLA4 Ig ameliorated the increases in arthritic score and paw thickness in the later phase, but not in the early phase of arthritis. CsA suppressed the increases in arthritic score and paw thickness in both the early and later phases of arthritis. CTLA4 Ig and CsA suppressed mRNA up-regulation of T-cell markers, CD3 and CD25, and immune response-related mediators, IFN-gamma and IL-12. They also suppressed the up-regulation of macrophage marker, F4/80, and proinflammatory cytokines, TNF-alpha, IL-1beta and IL-6. The results provide direct evidence that arthritis in this model is T-cell activation dependent.
19107087 [Salivary gland scintigraphy in the evaluation of patients with sicca complaints]. 2008 Oct Salivary gland scintigraphy is a non invasive method widely accepted as an objective assessment of salivary gland function and a diagnostic criterion of primary Sjögren's Syndrome. In this study we evaluated the performance of qualitative and semi--qualitative salivary gland scintigraphy in primary Sjögren's Syndrome. Additionally we aimed to identify the scintigraphic patterns of salivary gland involvement in this condition. PATIENTS AND METHODS: Observational study of fifty--six women with suspected primary Sjögren's Syndrome (pSS). Investigation included clinical history and observation, ophtalmologic examination, autoantibodies (SSA and SSB) determination, minor salivary gland biopsy and salivary gland scintigraphy interpreted according to Schall classification, visual quality of radioactivity uptake, morphology of time-activity curves and semi-quantitative parameters of uptake and excretion. RESULTS: Twenty patients fulfilled diagnostic criteria for pSS. Submandibular glands showed more pronounced functional impairment. In pSS patients, all scintigraphic parameters were significantly lower on these glands: a) qualitative evaluation ' visual quality of uptake (p=0,003), morphology of time-activity curves (p=0,001) and Schall classification (p<0,001); b) semi-quantitative parameters ' maximum counts (p=0,005), maximum counts/second/MBq administered (p=0,01), index of maximum counts versus counts at first minute (p=0,002) and excretion index (p=0,006). CONCLUSIONS: Despite being qualitative and observer-dependent, Schall classification is valuable for the diagnosis of primary Sjögren's Syndrome. Nevertheless, semi-quantitative evaluation of salivary gland scintigraphy reveals significant differences in pSS patients and may have incremental value for the interpretation of salivary gland scintigraphy results.
17278938 The role of exercise in the rehabilitation of patients with systemic lupus erythematosus a 2007 Mar PURPOSE OF REVIEW: The purpose of this review is to present an update on the evidence-based effects of exercise in systemic lupus erythematosus and in primary Sjögren's syndrome. RECENT FINDINGS: Physical capacity is reduced in both systemic lupus erythematosus and primary Sjögren's syndrome and fatigue is a dominating and disabling symptom in both conditions. The documentation on the effect of exercise on the rehabilitation of patients with systemic lupus erythematosus and primary Sjögren's syndrome is sparse; the studies are few and the sample sizes often small. The available studies indicate that patients with systemic lupus erythematosus of mild to moderate disease activity as well as patients with primary Sjögren's syndrome benefit from exercise of moderate to high intensity. Positive effects can be expected with regard to aerobic capacity, fatigue, physical function and depression. SUMMARY: There is reason to believe that exercise should be included in the rehabilitation of patients with mild to moderate systemic lupus erythematosus and patients with primary Sjögren's syndrome. Further research is needed and should aim to evaluate the effect of exercise on groups with varying degree of disease severity and to document the long-term impact on the disease.
16568213 Double-filtration plasmapheresis for resolution of corticosteroid resistant adult onset St 2006 Jul A 45-year-old Japanese male was diagnosed with adult onset Still's disease (AOSD). High-dose corticosteroid initially resolved the illness; however, high fever, maculopalpular rashes, arthralgia, and acute pericarditis rapidly recurred, and were followed by a somnolent state without focal signs. A diagnosis of corticosteroid resistant, severe, recurrent AOSD was made, and double-filtration plasmapheresis (DFPP) was performed immediately. The somnolent state began to resolve during the first plasmapheresis procedure, and the other symptoms resolved shortly thereafter. DFPP theoretically removes monocyte-activating cytokines, such as monocyte colony-stimulating factor (M-CSF) from the circulation, and therefore may prove to be an effective treatment for corticosteroid resistant, rapidly developing cases of AOSD.
17087339 [Case of rapid progressive interstitial pneumonia associated with primary Sjogren syndrome 2006 Oct A 72-year-old woman with a dry cough and dyspnea on exertion was admitted to our hospital. A chest radiograph showed reticular opacities and volume loss in both lower lung fields. She was troubled with xerostomia and her laboratory test showed positive reaction for anti SS-A and SS-B antibody. Labial biopsy led to a diagnosis of primary Sjogren's syndrome (pSjS). Lung biopsy specimens obtained by video-assisted thoracoscopic surgery (VATS) revealed interstitial pneumonia. On the sixth postoperative day, hypoxemia acutely worsened and her chest radiograph showed widespread diffuse ground-glass attenuation. A diagnosis of acute exacerbation was made, and steroid and immunosuppressive therapy was started. In spite of intensive therapy, she died due to respiratory failure. We report a rare case of interstitial pneumonia with pSjS resulting in acute exacerbation.
16453296 Peripheral neuropathy in an outpatient cohort of patients with Sjögren's syndrome. 2006 May Peripheral neuropathy is common in patients with Sjögren's syndrome (SS), but its precise prevalence is unknown. Most prior studies were conducted at neurology or rheumatology specialty clinics and likely selected for a more severely affected population. We evaluated 22 SS patients and 10 controls for evidence of neuropathy in an outpatient setting at a regional meeting of the Sjögren's Syndrome Foundation. We performed neurological examinations and nerve conduction studies (NCSs) and measured serum antinuclear antibody (ANA) and SS-A and SS-B antibody levels. Participants filled out a questionnaire pertaining to symptoms, diagnosis, and treatment. We found that signs and symptoms related to small axons were more common in patients with SS than in controls. Complaints of painful distal paresthesias in the feet were noted in 59% of patients but in only 10% of controls, and of abnormal sweating in 41% and 0%, respectively. Examination revealed decreased pinprick sensation in 64% of patients with SS, but in only 30% of controls. Overall, 45% of the patients but none of the controls were thought to have an isolated small-fiber neuropathy. Large-fiber dysfunction (as measured by testing vibration, deep tendon reflexes, and NCSs) was similar between the two groups. We conclude that small-fiber neuropathy is common in patients with SS.
18791828 Rapid and significant induction of TRAIL-mediated type II cells in apoptosis of primary sa 2008 Nov Expressions of the effector molecules of Fas-mediated apoptosis in primary cultured salivary gland epithelial cells (SGEC) of primary Sjögren's syndrome (pSS) remain to be clarified. We focused on Fas-mediated caspase cleavage compared to tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. Induction of apoptosis was performed by anti-Fas antibody coupled with PI3K inhibitor, or TRAIL. Activation of caspases, cytochrome C, and apoptotic protease activating factor-1 (Apaf-1) was determined by western blotting or immunofluorescence observed by confocal microscopy. Fas-mediated apoptosis and activation of caspase 3/8 were induced in the presence of LY294002. TRAIL-induced apoptosis in SGEC, which was stronger than that induced by anti-Fas antibody. TRAIL-induced caspase 9 cleavage accompanied by activation of cytochrome C and Apaf-1 were not mediated by anti-Fas antibody. Our results suggest that death receptor-dependent apoptosis in primary cultured SGEC is regulated by the engagement of type II cells in pSS.
18553114 Primary Sjögren's syndrome in men: clinical and immunological characteristic based on a l 2008 Dec The aim of the study was to define main symptoms of clinical appearance and immunoserological profile of male patients with primary Sjögren's syndrome (pSS). Four hundred and ninety-two patients fulfilling the European-American Consensus Criteria for pSS were involved in this study. The mean age of the patients was 55.93 years (55.67 years in women and 56.18 years in men). The female-male ratio was 7:1 (432 and 60 patients, respectively). At the time of the diagnosis of pSS, glandular, extraglandular manifestations (EGMs), and immunoserological parameters were assessed. The major EGMs differ between genders. Arthritis was frequently presented as EGM in both genders, but the ratio was higher in men (68% vs. 42%). Various vasculitis symptoms and lymphadenopathy were more frequent in men than in women, in contrast to Raynaud's phenomenon or autoimmune thyroiditis. Anti-SS-A and anti-SS-B were the most frequent autoantibodies in both genders, although autoantibodies against anti-nuclear factor and extractable nuclear antigens also presented in some patients. In a few cases, there were other specific autoantibodies correlated with EGMs, such as double-stranded DNA, anti-neutrophilic-cytoplasmic antibody, cyclic-citrullinated peptide, anti-thyreoglobuline antibodies, and anti-thyreoid-peroxidase antibodies. Based upon our large cohort of patients with pSS, we conclude that, although the disease is more frequent in women usually about climax, it develops also in men with the predominant symptoms of vasculitis or arthritis besides keratoconjunctivitis sicca or xerostomy.
17787040 Serological implications of germinal center-like structures in primary Sjögren's syndrome 2007 Oct OBJECTIVE: To determine serological implications of germinal center (GC)-like structures in primary Sjögren's syndrome (pSS). METHODS: Retrospectively, minor salivary gland biopsies (n = 269) with focal lymphoid aggregates corresponding to focus score > 1 were evaluated for the presence of GC-like morphology. Relevant clinical information was obtained from medical records. RESULTS: Of 269 patients, 169 fulfilled the American-European criteria for pSS. GC-like features were observed in 47/169 (28%) biopsies. In the majority of cases, GC-like lesions were confirmed by CD21-positive follicular dendritic cell networks. Mean inflammatory focus score was significantly higher in GC-positive compared to GC-negative samples (p < 0.001). GC-positive patients had lower mean salivary secretion (p < 0.001) and a higher frequency of patients with unstimulated salivary secretion < or = 1.5 ml/15 min (p < 0.01). In addition, elevated titers of rheumatoid factor, serum anti-Ro/SSA and anti-La/SSB (p < 0.05), and IgG levels > or = 15.3 g/l (p < 0.05) were more common in GC-positive compared to GC-negative. Enlarged salivary glands were observed in 46/163 (28%) patients, but could not be linked to either presence or absence of GC-like features. CONCLUSION: Inflammatory infiltrates with GC-like morphology were observed in 28% of the investigated patients with pSS, and was particularly noted in patients with higher focus score. The observed serological aberrations in patients with ectopic GC-like structures in the minor salivary glands warrant further prospective studies.