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ID PMID Title PublicationDate abstract
12465146 The use of infliximab in academic rheumatology practice: an audit of early clinical experi 2002 Dec OBJECTIVE: To audit a first clinical experience of treating rheumatic disease patients with infliximab in the setting of an academic tertiary care rheumatology practice. METHODS: The infusion history of patients referred to the McGill University Health Centre during the first 18 month period of a special access program for treatment with infliximab, a tumor necrosis factor-a antibody, was audited for disease characteristics, dosing schedule for infliximab, concomitant treatments, response rate, and side effect profile. RESULTS: Forty-one patients received a total of 300 infusions of infliximab over a period of 9 +/- 5 months (mean +/- standard deviation). Rheumatic disease indications were rheumatoid arthritis in 30, spondyloarthropathy in 6, psoriatic arthritis in 2, juvenile onset polyarthritis in 2, and scleroderma in one. Disease duration was 17 +/- 11 years. Concomitant treatment with steroids and methotrexate was present in 68% and 54%, respectively. Infliximab treatment was continued beyond 5 infusions or 22 weeks in 63%. Of the 26 patients continuing treatment, adjustment to dosing and/or interval schedule of infusions was made in 58%. The clinical response rate was moderately to greatly improved in 96%. Severe side effects considered directly related to the treatment were observed in 6 (15%) patients; less severe side effects, which did not preclude continuation of treatment but frequently required medical intervention, were noted in 93%. CONCLUSION: Infliximab is a valuable treatment for patients with resistant rheumatic diseases in the short term. Both the serious, and the frequent, more benign complication rate observed in this group of patients should alert physicians to be vigilant in the routine care of patients treated with infliximab.
11792875 Outcome in patients with idiopathic inflammatory myositis: morbidity and mortality. 2002 Jan OBJECTIVE: To assess the long-term outcome of a cohort of 46 patients with idiopathic myositis by assessing both health status, as measured by the SF-36, and cumulative survival probability over a 20-yr follow-up period at a single rheumatology centre. Methods and results. Forty-six patients under long-term follow-up from 1978 to 1999 were identified from our database. All patients fulfilled three out of four of the Bohan and Peter criteria for myositis. We excluded those with malignancy-associated disease and those with inclusion body myositis. Twenty-three patients (50%) had adult-onset polymyositis, 14 (30.4%) had adult-onset dermatomyositis, one had childhood-onset dermatomyositis and eight (17.4%) had an overlap syndrome (associated with either systemic lupus erythematosus or rheumatoid arthritis). During the course of the disease, seven patients (15.2%) went into full remission, eight (17.4%) had monophasic illness, nine (19.6%) had a relapsing-remitting course, 16 (34.8%) had chronic progressive illness and six (13.04%) died. All patients had significantly lower SF-36 scores in all aspects of health compared with the general population (P< or =0.001). Patients with chronic progressive illness had significantly greater bodily pain (P< or =0.05, t-test) than those with a relapsing-remitting illness, but did not differ in other aspects of health. There was no significant difference in the scores in the different domains of the SF-36 between the patients with active disease and those with inactive disease (0.05
15124258 Rheumatic disease in an Australian Aboriginal community in North Queensland, Australia. A 2004 May OBJECTIVE: To estimate prevalences of rheumatic diseases in Aboriginal Australians. METHODS: The methodology of the Community Oriented Program for the Control of Rheumatic Diseases (COPCORD) was followed. Everyone aged 15 years or older in Yarrabah, North Queensland, was invited to complete a COPCORD Core Questionnaire. Aboriginal health workers carried out a house-to-house survey during January 2002. People reporting current musculoskeletal symptoms and 56 others (controls) were examined at the community health center. RESULTS: Eighty percent of the target population was covered during the survey. Eight hundred and forty-seven questionnaires were completed (47% men) and 135 people refused, a response of 86%. Rheumatic symptoms within the previous 7 days were reported by 33% and past symptoms by 22%. The most common sites of current pain were low back (12.5%), knee (11.2%), and shoulder (8.9%). Sixty-seven people (7.7%) said activities were limited by their symptoms. Two hundred and sixty-three people were examined, and the most common diagnoses were soft tissue pain (point prevalence 7.4%), osteoarthritis (5.5%), and low back pain (4.3%). The cumulative prevalence of gout was 7.0% in men and 0.9% in women over the age of 15 years. The relative risk of gout associated with drinking regularly was 2.5, and with body mass index > 25 was 3.3. No rheumatoid arthritis or systemic lupus erythematosus cases were identified, but there were 4 cases of psoriatic arthritis (point prevalence 0.5%). CONCLUSION: This is the first unselected population study of rheumatic diseases in Australian Aboriginals. There was a high prevalence of gout among men, with modifiable factors of weight and alcohol identified.
12745747 Intercurrent autoimmune conditions in classic and non-ulcer interstitial cystitis. 2003 OBJECTIVE: Interstitial cystitis (IC) is known to be one of the most bothersome conditions encountered in urological practice. It is frequently divided into two subtypes: classic and non-ulcer. Several authors have reported on autoantibodies in patients with IC and clinical and histopathological findings show similarities with those in some autoimmune disorders. Furthermore, IC has been shown to be associated with autoimmune diseases such as systemic lupus erythematosus, Sjögren's syndrome and autoimmune diseases of the thyroid gland. Our aim was to study the occurrence of associated autoimmune conditions in patients with IC diagnosed according to the National Institutes of Health/National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases criteria. MATERIAL AND METHODS: Our sample of IC patients consisted of 129 with classic IC and 93 with non-ulcer IC. Clinical records, including micturition charts, were surveyed, and a more in-depth interview was obtained by means of a telephone call. Autoimmune disorders, diagnosed by Swedish clinicians according to acknowledged diagnostic criteria, were registered. RESULTS: Allergy was the most common IC-associated condition, 41% of all patients with classic IC and 47% of all patients with non-ulcer IC having some type or degree of hypersensitivity/allergy. Rheumatoid arthritis occurred in 13% of patients with classic IC and in 4% with non-ulcer IC. Inflammatory bowel disease was not diagnosed in any of the patients with non-ulcer IC whereas 2.3% of the patients with classic IC had either ulcerative colitis or Crohn's disease, approximately 33 times the prevalence seen in the general population. CONCLUSION: It appears that systemic and autoimmune disorders are more prevalent in the IC population than in the general population.
12528110 Control of fibroblast-like synoviocyte proliferation by macrophage migration inhibitory fa 2003 Jan OBJECTIVE: The hyperplasia of fibroblast-like synoviocytes (FLS) is considered essential to the evolution of joint destruction in rheumatoid arthritis (RA), but the mechanisms underlying FLS proliferation remain poorly understood. Macrophage migration inhibitory factor (MIF) is a cytokine that has recently been shown to exert proinflammatory effects on RA FLS. This study sought to identify the mechanisms of activation of FLS by MIF, and to assess the effects of MIF on synovial cell proliferation. METHODS: Human RA FLS were treated with recombinant MIF, interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and/or anti-MIF monoclonal antibodies (mAb). Proliferation was measured with tritiated thymidine incorporation. Nuclear factor kappa B (NF-kappa B) and mitogen-activated protein (MAP) kinase activation were measured with immunohistochemistry and Western blotting, respectively. RESULTS: FLS proliferation was significantly increased by MIF. IL-1 beta and TNFalpha also induced proliferation, but these effects were prevented by neutralization with anti-MIF mAb. Activation of NF-kappa B was induced by IL-1 beta, but not by MIF. Anti-MIF mAb had no effect on IL-1 beta-induced NF-kappa B nuclear translocation. By contrast, MIF induced phosphorylation of extracellular signal-regulated kinase (ERK) MAP kinase. ERK antagonism, but not NF-kappa B antagonism, prevented the effect of MIF on FLS proliferation. CONCLUSION: These data suggest that MIF may regulate RA synovial hyperplasia by acting directly and via involvement in the effects of IL-1 beta and TNFalpha. In addition, the effects of MIF on FLS activation are independent of NF-kappa B, and dependent on ERK MAP kinase. These data suggest an important therapeutic potential for MIF antagonism in RA.
15551286 Response of factor V inhibitor to rituximab in a patient who received liver transplantatio 2004 Dec A 43-year-old patient developed factor V inhibitor 6 months after liver transplantation for primary biliary cirrhosis in association with Sjogren's syndrome/systemic lupus erythematosus. She suffered from ecchymoses in the lower extremities. The factor V inhibitor was eradicated after 10 weekly doses of 375-500 mg/m2 rituximab.
11835350 T-gamma large granular lymphocyte leukemia associated with amegakaryocytic thrombocytopeni 2002 Feb We present a female patient with T-gamma LGL leukemia, who was followed for the last 20 years. Over these years she developed several autoimmune disorders, including Sjögren's syndrome, Hashimoto's thyroiditis, premature ovarian failure (compatible with type II autoimmune polyglandular syndrome), amegakaryocytic thrombocytopenic purpura, and finally pure red cell aplasia. PCR analysis confirmed rearrangement for TCR gamma. This case emphasizes the complex association of LGL leukemia with autoimmune disorders.
12603525 Incidence of Sjögren's syndrome in Japanese patients with hepatitis C virus infection. 2003 Mar BACKGROUND AND AIM: Hepatitis viruses induce not only chronic liver diseases but also the impairment of other organs and tissues as extrahepatic manifestations. In particular, hepatitis C virus (HCV) is involved in various extrahepatic manifestations. The purpose of the present study was to evaluate Sjögren's syndrome (SS) and lichen planus (LP) involvement, which are various extrahepatic manifestations in patients with liver diseases related to hepatitis B virus (HBV) or HCV. METHODS: We examined a total of 110 Japanese patients with chronic liver disease: 29 with HBV infections and 81 HCV infections. RESULTS: The prevalence of SS according to European and Japanese criteria in patients with chronic HCV infection was significantly higher than in patients with chronic HBV infection (European criteria: 25.9 vs 3.4%; P < 0.05, Japanese criteria: 21.0 vs 3.4%; P = 0.05). Lichen planus was observed in one (3.4%) of 29 patients with chronic HBV infection, and in 11 (13.6%) of 81 patients with chronic HCV infection. Simultaneously combined LP and SS occurred in 8.6% (seven of 81) of patients with HCV infection, but in none with HBV infection. CONCLUSIONS: Clinicians should routinely follow the HCV-infected patients, paying sufficient attention to the presence of SS and LP, and they should also carefully monitor their prognosis.
11997071 Motor weakness and cerebellar ataxia in Sjögren syndrome--identification of antineuronal 2002 May 15 We report here a combination of rare neurological manifestations of primary Sjögren syndrome (SS), such as motor-dominant motor weakness of peripheral origin, cerebellar ataxia and depression, in a Japanese female patient. An autoantibody in her serum and cerebrospinal fluid immunolabelled spinal motor neurons and cerebellar Purkinje cells. On Western blot, this antibody reacted with a protein of 34 kDa from the extract of spinal cord, dorsal root ganglion, or cerebellar cortex, which might correspond to motor weakness and cerebellar ataxia, respectively. The absence of its reactivity to the liver tissue indicates that this autoantibody targets an antigen represented exclusively in the neural tissues. Although it remains to be proved how autoantibodies, sometimes associated with SS, are involved in the development of clinical pictures, some of them are present in the cerebrospinal fluid and exhibit an exclusive affinity to neural tissues, which indicates its plausible link to neurological manifestations. Recognition of these antineuronal antibodies in SS will potentially provide a chance to treat these patients by removing or inactivating the antibody.
12931489 [Cardiac involvement in systemic autoimmune disease]. 2003 Apr Systemic autoimmune diseases form a diverse group which includes: systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma, dermato-polymyositis, Wegener's granulomatosis, Sjögren syndrome. Although multisystem involvement is the hallmark of these diseases, the heart seems to be less affected than other organ systems. The aim of the study was to study possible cardiac abnormalities in patients with documented systemic autoimmune diseases and to assess whether there was any relation between antiphospholipid, anti-dsDNA antibodies and myocardial dysfunction findings. 76 patients (53 with SLE, 9 with MCTD, 8 with scleroderma, 6 with Wegener's granulomatosis) were subjected to our study, 69% of these patients manifested cardiac involvement, based on two-dimentional echocardiografic examination (36%--post-inflammatory valvular thickening, 20%--pericardial effusions, 15%--valvular regurgitation, 7%--left atrial enlargement, 5%--left ventricular hypertrophy, 4%--left ventricular dysfunction). None of the patients showed characteristic, acute Libman-Sacks endocarditis, which probably can be explained by chronic corticosteroid-treatment. Clinical evidence of cardiac abnormalities has been observed, in as many as 58% of cases with positive echocardiographic findings. The frequency and extend of cardiac pathology positively correlated with the detection of antiphospholipid antibodies. No such relationship was observed in patients with the presence of very high titers of antinuclear antibodies (anti-dsDNA). In conclusion, our results indicate that echocardiography is a useful method for assessment and monitoring cardiac involvement in the systemic autoimmune diseases.
15554428 Hepatitis C virus-associated extrahepatic manifestations: a review. 2004 Dec The hepatitis C virus (HCV) infection is a worldwide disease that is characterized by a preferential chronic evolution with mild to severe liver disease, including cirrhosis and, in lesser proportion, hepatocarcinoma. Out of these complications, HCV is frequently reported to complicate extrahepatic manifestations. Among those associated to HCV infection with a high degree of certainty, mixed cryoglobulinemia and its complications (skin, neurological, renal, rheumatological involvement) are the most prevalent (50%) in HCV-infected patients. The other diseases include noncryoglobulinemic systemic vasculitis, splenic lymphoma with villous lymphocytes, fatigue, porphyria cutanea tarda, sicca syndrome, and autoantibodies production. The extrahepatic manifestations that share mild-degree certainty of association with HCV infection include B-cell non-Hodgkin lymphoma, autoimmune thrombocytopenia, pruritus, and type II diabetes mellitus. The other diseases such as autoimmune thyroiditis, lichen planus are more questionable for their eventual association with HCV and others (pulmonary fibrosis with or without polymyositis, progressive encephalomyelitis, Mooren's corneal ulcers, erythema nodosum, chronic polyradiculonevritis) are mostly case reports. Howerver, even in cases of tight association, the mechanisms through which HCV may promote or induce extrahepatic manifestations remain unclear and merit further investigations.
15213331 Enhanced DNA-dependent protein kinase activity in Sjögren's syndrome B cells. 2004 Sep OBJECTIVE: To examine the stress response, including the role of DNA-dependent protein kinase (DNA-PK), in B cells from Sjögren's syndrome (SS) patients. METHODS: B-cell lines were exposed to gamma radiation and then postincubated to allow inducible stress functions to develop. The magnitude of the DNA damage response was monitored with respect to DNA-PK phosphorylation of a p53 peptide, defence protein levels (Ku, DNA-PK catalytic subunit, ATM, p21 and p53) and flow cytometric determination of cell cycle phases and apoptosis. RESULTS: B cells from SS patients, compared with healthy controls, displayed enhancement of two stress functions in undamaged cells: DNA-PK kinase activity and apoptosis. In addition, SS showed enhanced cell cycle arrest in gamma-irradiated cells. CONCLUSIONS: Strong kinase activity of DNA-PK, functioning not only in a DNA damage response but also in immunoglobulin gene rearrangement, may be an important component of the heightened stress response displayed by SS cells. In combination with recent reports, our data indicate that constitutional hyper-reactivity to danger signals is a basic pathogenetic factor in SS.
12737324 Serum and salivary neopterin and interferon-gamma in primary Sjögren's syndrome. Correlat 2003 OBJECTIVE: To investigate serum and salivary neopterin and interferon-gamma as possible markers of immune system activation in primary Sjögren's Syndrome (pSS). METHODS: Serum and salivary neopterin and interferon-gamma concentrations were determined in 30 untreated patients with pSS and matched with several other clinical and laboratory parameters. RESULTS: The mean concentration of neopterin was significantly higher in pSS patients (8.12+/- 3.36 nmol/L in serum and 9.50 +/-7.61 nmol/L in saliva) than in normal controls (p<0.05). Significant correlations were found between serum neopterin and beta2-microglobulin, serum IgG as well as lip biopsy score. Salivary neopterin concentration was inversely related to Shirmer-I test, tear break-up time and stimulated salivary flow rate. Serum and salivary levels of interferon-gamma were normal and no correlation with the other parameters was found. CONCLUSION: In pSS patients serum neopterin may represent a useful marker of cell-mediated immunity. On the other hand, salivary neopterin seems to reflect theglandular damage.
12666137 Pure red cell aplasia in a Sjögren's syndrome/lupus erythematosus overlap patient. 2003 Apr Hematological complications of systemic lupus erythematosus usually include anemia of chronic disease and peripheral destruction of blood cells. We describe the case of a young woman with Sjögren's syndrome'lupus erythematosus overlap, mother of infant with congenital heart block, complicated by pure red cell aplasia. The patient was asymptomatic until the onset of severe anemia. A serum inhibitor of erythropoiesis was detected before the onset of immunosuppression. Bone marrow examination showed a low CD4:CD8 ratio, an immune defect possibly linked with the unrestrained production of antibodies against erythroid progenitor cells.
12064854 Cutaneous T cell lymphoma in a patient with primary biliary cirrhosis and secondary Sjögr 2002 Jun We describe a patient with primary biliary cirrhosis (PBC) and secondary Sjogren's syndrome (SS) with pulmonary involvement who developed a cutaneous T cell lymphoma. The clinical course of secondary SS in PBC is thought to be less complicated than in progressive systemic scleroderma and SS. In contrast to secondary SS, the risk for developing non-Hodgkin's lymphoma is highly increased in patients with primary SS. Moreover, these lymphomas are usually of B cell origin. There are few reports of T cell lymphoma in primary SS. The occurrence of a T cell lymphoma in a patient with PBC and secondary SS indicates the necessity to investigate lymphoma in patients with secondary SS.
11878203 General pharmacological profile of the novel muscarinic receptor agonist SNI-2011, a drug 2002 A novel muscarinic receptor agonist SNI-2011 ((+/-)-cis-2-methylspirol[1,3-oxathiolane-5,3'-quinuclidine] monohydrochloride hemihydrate, cevimeline, CAS 153504-70-2), is a candidate therapeutic drug for xerostomia in Sjögren's syndrome. The general pharmacological properties of this drug on the somatic nervous system and on the autonomic nervous system and smooth muscle were investigated in mice, rats, guinea pigs, rabbits and cats. 1. Somatic nervous system: SNI-2011 had no effect on the neuromuscular junction in rats and no muscle relaxant effect in mice. No surface anesthetic effect was observed in guinea pigs, but infiltration anesthetic effect was found after intracutaneous injection of solution (1% or higher). 2. Autonomic nervous system and smooth muscle: SNI-2011 tended to cause mydriasis at 3 mg/kg i.v. or higher in rabbits and dose-dependently caused mydriasis at 10 mg/kg p.o. or higher in rats. Mydriasis in rats was also observed by ophthalmic instillation, caused via the peripheral muscarinic acetylcholine receptors. SNI-2011 elevated the base line tension of nictitating membrane in cats when it was injected intravenously at 3 mg/kg or higher. In the smooth muscle, SNI-2011 increased the spontaneous movement of isolated rabbit ileum (1 x 10(-6) mol/l or higher), contractions of isolated guinea pig ileum (1 x 10(-6) mol/l or higher) and isolated guinea pig trachea (3 x 10(-6) mol/l or higher). SNI-2011 relaxed the histamine- and noradrenaline-induced contractions of isolated guinea pig aorta and augmented noradrenaline- and phenylephrine-induced contractions of isolated rat vas deferens. These effects were induced by relatively higher concentrations only i.e. 1 x 10(-5) mol/l or higher. From these results, SNI-2011 has muscarinic side effects on the somatic nervous system and on the autonomic nervous system and smooth muscle, however, in the case of oral administration, that is clinical administration route, SNI-2011 caused no muscarinic side effect at the effective doses needed for saliva secretion.
15451477 Human mAChR antibodies from Sjögren syndrome sera increase cerebral nitric oxide synthase 2004 Nov We demonstrated the presence of circulating antibodies from Sjögren syndrome (SS) patients enable to interact with rat cerebral frontal cortex by activating muscarinic acetylcholine receptors (mAChRs). IgG from SS and IgG from normal subjects were studied by flow cytometry, enzyme immunoassay (ELISA), and radioligand binding assays. By flow cytometric and ELISA procedures, it was shown that IgG from SS patients reacted to cerebral frontal cortex cell surface. SS IgG was able to interact with mAChR by inhibiting 3H-QNB binding to its specific receptor. Besides, SS IgG displayed an agonistic-like activity associated to specific M1 and M3 mAChR activation, increasing nitric oxide synthase (NOS) isoform activities. Neuronal (n) and endothelial (e) NOS-mRNA gene expression of rat frontal cortex is induced by SS IgG. This article supports the participation of humoral immune alterations in SS, resulting in central parasympathetic functional deregulation. These antibodies alter mAChR activation, NOS activity, and eNOS and nNOS gene expression.
15272896 CSF isoelectrofocusing in a large cohort of MS and other neurological diseases. 2004 Aug The present study was performed in order to confirm the diagnostic value of isoelectrofocusing (IEF) in a large multiple sclerosis (MS) cohort and to evaluate the various neurological diseases probably to present a similar IEF profile. The cerebrospinal fluid (CSF) of 1292 patients with neurological diseases was studied by IEF. After a follow-up of 2-36 months, we only included patients with a definite MS or confirmed diagnosis of other neurological diseases (OND). MS was diagnosed in 407 patients and OND in 593 patients. For patients in whom three or more oligoclonal bands (OCB) were detected, IEF results showed a sensitivity of 85% and a specificity of 92% for the diagnosis of MS. The positive and negative predictive values were 86.5 and 90%, respectively. Inflammatory and infectious disorders of the central nervous system represented the main affections associated with OCB, including human immunodeficiency virus encephalitis, Lyme disease and less frequently Sjogren syndrome. Furthermore, when OCB were observed, 10 or more bands were more frequently found in MS than in OND (P < 0.0001). IEF of the CSF is a reliable method for the diagnosis of MS. The absolute number of bands may help to discriminate between MS and OND.
12428060 Unmasking the anti-La/SSB response in sera from patients with Sjogren's syndrome by specif 2002 Jun BACKGROUND: Autoantigen La/SSB is molecular target of humoral autoimmunity in patients with primary Sjogren's Syndrome (pSS) and systemic lupus erythematosus (SLE). In this study, we investigated the existence and possible influence of anti-idiotypic response to anti-La/SSB antibodies. MATERIALS AND METHODS: Synthetic peptide analogs (pep) of the major antigenic determinants of La/SSB (289-308 aa and 349-364 aa) were prepared. Based on "molecular recognition" theory, complementary peptides (cpep), derived by anti-parallel readings of the noncoding strand of La/SSB DNA encoding for its antigenic determinants, were constructed. Sera from 150 patients with anti-La/SSB antibodies, 30 patients without anti-La/SSB antibodies, and 42 normal individuals were tested against all four peptides. F(ab')(2) fragments from anti-peptide IgG were prepared and F(ab')(2) - IgG interactions were evaluated using a specific anti-idiotypic ELISA. RESULTS: All four peptides were recognized by anti-La positive sera (83% and 51% for pep and cpep 349-364 and 51% and 28% for pep and cpep289-308, respectively). Anti-cpep F(ab')(2 )bound to a common idiotype (Id) located within or spatially close to the antigen combining site of anti La/SSB (anti-pep) antibodies. Homologous and cross-inhibition experiments further confirmed this relation. The anti-idiotypic antibodies inhibited the anti-La/SSB antibody binding to recombinant La/SSB by 91%. To overcome the anti-idiotypic interference in anti-La/SSB detection, a specific assay was developed. Sera were heated for dissociation of Id-anti-Id complexes, anti-Id antibodies blocked with cpep, and anti-La/SSB reactivity was recovered. Application of this method to anti-Ro positive-anti-La/SSB "negative" sera showed that all anti-Ro/SSA positive autoimmune sera also possess anti-La/SSB antibodies. This reaction was not observed in 14 anti-Ro negative- anti-Sm/RNP positive sera from patients with SLE. CONCLUSIONS: Autoimmune sera from patients with pSS and SLE contain anti-idiotypic antibodies targeting a common anti-La/SSB idiotype. These antibodies can be detected using complementary peptides of La/SSB epitopes. The antiidiotypic antibodies mask the anti-La/SSB response. Hidden anti-La/SSB antibodies can be released and detected using complementary epitope analogs.
13130477 Enhanced degradation of proteins of the basal lamina and stroma by matrix metalloproteinas 2003 Sep OBJECTIVE: To determine the effect of matrix metalloproteinase (MMP) activity from the labial salivary glands (LSGs) of Sjögren's syndrome (SS) patients on proteins of the extracellular matrix (ECM) that form the basal lamina and stroma, and to compare this effect with the structural integrity of acini and ducts as well as the functionality of the LSGs. METHODS: Gelatinase activity was determined by zymography. The digestion pattern of extracellular matrix (ECM) macromolecules was detected by gel electrophoresis and quantified by densitometry. The structural integrity of acini and ducts was evaluated by light and electron microscopy. Secretory function was evaluated by measuring unstimulated salivary flow and by scintigraphy. RESULTS: LSG extracts showed increased levels of proteolytic activity toward purified proteins of the basal lamina (laminin and type IV collagen) and stroma (types I and III collagen and fibronectin). Enhanced degradation was most evident for fibronectin, laminin, and type IV collagen. Analysis of the ultrastructure of the acinar and ductal basal lamina revealed abnormalities ranging from disorganization to disappearance of this ECM structure. These changes were paralleled by an important loss of microvilli on the apical surface, as well as decreased unstimulated salivary flow. Interestingly, the results were similar in LSGs from all SS patients, regardless of the proximity of infiltrating mononuclear cell foci. CONCLUSION: Our observation that the proteolytic action of MMPs toward ECM macromolecules is increased in SS patients provides a rationale for understanding the dramatic changes in the structural organization observed in the basal lamina and apical surface of acini in these patients. The results provide new evidence that acinar and ductal cells from the LSGs of SS patients display a molecular potential, with increased capacity to markedly disorganize their ECM environment and, thus, damage their architecture and functionality.