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ID PMID Title PublicationDate abstract
15975969 Effect of human vasoactive intestinal peptide gene transfer in a murine model of Sjogren's 2006 Feb BACKGROUND: Sjögren's syndrome (SS), an autoimmune exocrinopathy mainly affecting lachrymal and salivary glands, results in ocular and oral dryness (keratoconjunctivitis sicca and xerostomia). The aetiology and pathogenesis are largely unknown; currently, only palliative treatment is available. OBJECTIVE: To determine whether gene transfer of vasoactive intestinal peptide (VIP), based on its immunomodulatory properties, might be useful in the management of SS. METHODS: A recombinant serotype 2 adeno-associated virus encoding the human VIP transgene (rAAV2hVIP) was constructed and its efficacy tested in the female non-obese diabetic (NOD) mouse model for SS after retrograde instillation in submandibular glands (SMGs). 10(10) particles/gland of rAAV2hVIP or rAAV2LacZ (encoding beta-galactosidase; control vector) were administered at 8 weeks of age (before sialadenitis onset). Salivary flow rates were determined before vector delivery and at time of death (16 weeks). After death, saliva, serum, and SMGs were harvested. Salivary output, inflammatory infiltrates (focus scores), VIP protein expression, cytokine profile, and serum anti-VIP antibodies were analysed. RESULTS: rAAV2hVIP significantly improved the salivary flow, increased SMG and serum expression of VIP, and reduced SMG cytokines interleukin (IL) 2, IL10, IL12 (p70), and tumour necrosis factor alpha, and serum RANTES, compared with the control vector. No difference in focus scores or apoptotic rates was found; neutralising antibodies were not detected. CONCLUSIONS: Local delivery of rAAV2hVIP can have disease modifying and immunosuppressive effects in SMGs of the NOD mouse model of SS. The new strategy of employing VIP prophylactically may be useful for both understanding and managing the salivary component of SS.
18992010 Spinal cord biopsy findings of anti-aquaporin-4 antibody-negative recurrent longitudinal m 2009 Aug We describe the pathological features of a spinal cord biopsy from a 69-year-old woman with anti-aquaporin-4 antibody-negative recurrent longitudinal myelitis. Spinal cord MRI showed T2 high-intensity lesions with strong gadolinium enhancement, when episodes of sensory-motor impairment were repeated. The radiological abnormality was corrected by corticosteroid administration, but improvement of the symptoms was minimal. Although the patient had sicca symptoms and fulfilled four of the diagnostic criteria for Sjögren syndrome, the diagnosis was excluded, because of infection with hepatitis C virus, an exclusion criterion of Sjögren syndrome. In the spinal cord lesions, necrotic changes affected both myelin and axons. Infiltrating lymphocytes were predominantly T-cells. The proliferation of small vessels with hyalinization and concomitant occlusive change was remarkable. These pathological findings resembled those previously reported in Sjögren syndrome. Ultrastructurally, the endothelial cells of the small vessels showed features of activated cells and contained vesiculo-tubular structures in the cytoplasm, indicating that increased blood-brain barrier (BBB) permeability might contribute to pathogenesis. We speculated that increased BBB permeability and T-cell entry in the spinal parenchyma triggered pathological reactions resulting in necrotic changes in the spinal cord. Obstruction of small vessels might add ischemic damage to the lesions. The clinical course and pathological findings indicated that damage progressed rapidly in the spinal cord and was irreversible. The lesions apparently differed from typical demyelination plaques. Faced with such spinal cord lesions, a preventive therapeutic approach is necessary to avoid attack-associated disability.
18565216 Altered fractalkine cleavage potentially promotes local inflammation in NOD salivary gland 2008 INTRODUCTION: In the nonobese diabetic (NOD) mouse model of Sjögren's syndrome, lymphocytic infiltration is preceded by an accumulation of dendritic cells in the submandibular glands (SMGs). NOD mice also exhibit an increased frequency of mature, fractalkine receptor (CX3C chemokine receptor [CX3CR]1) expressing monocytes, which are considered to be precursors for tissue dendritic cells. To unravel further the role played by fractalkine-CX3CR1 interactions in the salivary gland inflammation, we studied the expression of fractalkine in NOD SMGs. METHODS: We studied protein expression using Western blot analysis of whole tissue lysates. Protease activity was measured in salivary gland tissue lysates using fluorimetric substrates. Digestive capacity of enzymes was determined by in vitro incubation of recombinant enzyme and fractalkine, followed by protein staining and Western blot. RESULTS: Fractalkine was detected in salivary glands of both NOD and control mice at all ages. Western blot analysis showed fractalkine cleavage with increasing age, which was more pronounced in NOD mice. This cleavage resulted in a decrease in the 31 kDa form of the protein, and the generation of an approximately 19 kDa band. Furthermore, in NOD animals older than 15 weeks, we noted the presence of a unique approximately 17 kDa fragment. This cleavage was organ specific, because it did not occur in brain or pancreas. Increased gelatinase and alpha-secretase activity were detected in NOD SMG and contributed to cleavage of the 31 kDa protein. Because aberrant cleavage products may induce autoimmunity, we studied the presence of autoantibodies against fractalkine. Indeed, NOD mice exhibited significantly more antibodies against fractalkine than did control animals. CONCLUSION: These data indicate that aberrant proteolytic activity in the NOD SMG results in increased fractalkine cleavage and generation of a unique fractalkine fragment. This specific cleavage may contribute to autoimmunity.
18249005 Evidence that anti-muscarinic antibodies in Sjögren's syndrome recognise both M3R and M1R 2008 Jul Inhibitory anti-muscarinic receptor type 3 (M3R) antibodies may contribute to the pathogenesis of Sjögren's syndrome (SS), and putative anti-M3R blocking antibodies in intravenous immunoglobulin (IVIg) have been suggested as a rationale for treatment with IVIg. We investigated the presence of subtype-specific anti-MR autoantibodies in healthy donor and SS sera using MR-transfected whole-cell binding assays as well as M1R and M3R peptide ELISAs. Control antibodies against the second extracellular loop of the M3R, a suggested target epitope, were induced in rabbits and found to be cross-reactive on the peptides M3R and M1R. The rabbit antibodies had neither an agonistic nor an antagonistic effect on M3R-dependent ERK1/2 signalling. Only one primary SS (out of 5 primary SS, 2 secondary SS and 5 control sera) reacted strongly with M3R transfected cells. The same SS serum also reacted strongly with M1R and M2R transfectants, as well as M1R and two different M3R peptides. Strong binding to M1R and low-level activities against M3R peptides were observed both in SS and control sera. IVIg showed a strong reactivity against all three peptides, especially M1R. Our results indicate that certain SS individuals may have antibodies against M1R, M2R and M3R. Our results also suggest that neither the linear M3R peptide nor M3R transfectants represent suitable tools for discrimination of pathogenic from natural autoantibodies in SS.
18050195 Rates of infiltration by macrophages and dendritic cells and expression of interleukin-18 2007 Dec OBJECTIVE: To evaluate the expression profile of infiltrating macrophages and dendritic cells (DCs) as well as of interleukin-18 (IL-18) and IL-12 in the minor salivary gland (MSG) lesions of patients with Sjögren's syndrome (SS), and to assess the relationship of these factors with disease parameters. METHODS: Macrophages, DCs, T cells, B cells, proIL-18, mature IL-18, and IL-12 were detected by single- and double-labeling immunohistochemistry in MSG specimens from 21 patients with primary SS (13 of 21 tested for IL-12), 7 patients with secondary SS, and 9 disease control patients. Expression profiles were assessed for correlations with various disease parameters, including adverse predictors of lymphoma development. RESULTS: MSGs from patients with SS (but not from disease controls) manifested increased infiltration by macrophages and DCs, strong expression of IL-18 by macrophages (particularly in B cell-rich areas and in germinal center-like structures in primary SS), and expression of IL-12 by mononuclear cell infiltrates. In primary SS, high infiltration by macrophages correlated with SG enlargement (P = 0.01). The DC infiltration rate correlated positively with the macrophage infiltration rate (P = 0.04), occurrence of SG enlargement (P = 0.03), and presence of C4 hypocomplementemia (P = 0.05), and inversely with serum C4 complement levels (P = 0.001). The rate of infiltration by IL-18-expressing cells correlated positively with biopsy focus scores (P < 0.001), larger infiltrates of macrophages (P = 0.01), DCs (P = 0.01), and B cells (P = 0.02), and SG enlargement (P = 0.02), and negatively with serum C4 complement levels (P = 0.02). The rate of infiltration by IL-12-expressing cells correlated inversely with that by IL-18-expressing cells (P = 0.001), biopsy focus scores (P = 0.003), and SG enlargement (P = 0.01), and positively with serum C4 complement levels (P = 0.05). CONCLUSION: In patients with primary SS, infiltration of the SG by macrophages and DCs and expression of IL-18 and IL-12 appear to play active roles in the expansion and organization of infiltrative injuries and have a correlation with certain predictors of lymphoma development.
17221876 Sensory ataxic neuropathy and esophageal achalasia in a patient with Sjogren's syndrome. 2007 Apr We describe a patient who developed an ataxic sensory syndrome associated with xerophthalmia and progressive dysphagia with regurgitation. Electrophysiological findings were consistent with an axonal sensory neuropathy, and superficial peroneal nerve biopsy showed a reduction in number of myelinated fibers with epineurial inflammation. Rheumatoid factor, anti-SSA/SSB and antinuclear antibodies were positive and a diagnosis of Sjogren's syndrome was made. An endoscopic investigation revealed esophageal achalasia. We suggest that there may be a common autoimmune mechanism directed to different targets on the basis of this rare association.
16143330 Pathological keratinisation in the conjunctival epithelium of Sjögren's syndrome. 2006 Mar Our previous gene expression analysis suggested that conjunctival epithelial cells of Sjögren's syndrome (SS) are inclined to hyper-proliferation and keratinisation status. The goal of this study is to elucidate whether such pathological situations really exist in the conjunctival epithelium of SS. Also, involvement of inflammatory cytokines in this disease was investigated. Conjunctival tissues or cells obtained from 12 SS patients and 13 normal subjects were subjected to indirect immunostaining to analyse expression of transglutaminase 1 (TGase1), involucrin, keratins 1, 4, 10 and 13. The number of proliferative cells was also analysed by immunostaining of Ki67 antigen. Additionally, changes in gene expression of TGase1 and involucrin after stimulation by IL-1 or IFN-gamma were quantified by real-time RT-PCR. TGase1 and involucrin were up-regulated in the conjunctival epithelium of SS patients. Although not statistically significant, Ki67 positive proliferative cells were slightly increased in SS patients. IFN-gamma stimulation significantly up-regulated TGase1 and unexpectedly repressed involucrin gene expression. IL-1 did not render any significant changes in the expression of these genes. These results suggest the existence of pathological keratinisation in the conjunctival epithelium of SS and also support our hypothesis that inflammatory cytokines may be involved in the ocular surface pathological changes in SS.
17335973 A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementa 2007 May Between 40% and 60% of Americans use complementary and alternative medicine to manage medical conditions, prevent disease, and promote health and well-being. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been used to treat joint pain associated with several inflammatory conditions. We conducted a meta-analysis of 17 randomized, controlled trials assessing the pain relieving effects of omega-3 PUFAs in patients with rheumatoid arthritis or joint pain secondary to inflammatory bowel disease and dysmenorrhea. Meta-analysis was conducted with Cochrane Review Manager 4.2.8. for six separate outcomes using standardized mean differences (SMDs) as a measure of effect size: (1) patient assessed pain, (2) physician assessed pain, (3) duration of morning stiffness, (4) number of painful and/or tender joints, (5) Ritchie articular index, and (6) nonselective nonsteroidal anti-inflammatory drug consumption. Supplementation with omega-3 PUFAs for 3-4 months reduces patient reported joint pain intensity (SMD: -0.26; 95% CI: -0.49 to -0.03, p=0.03), minutes of morning stiffness (SMD: -0.43; 95% CI: -0.72 to -0.15, p=0.003), number of painful and/or tender joints (SMD: -0.29; 95% CI: -0.48 to -0.10, p=0.003), and NSAID consumption (SMD: -0.40; 95% CI: -0.72 to -0.08, p=0.01). Significant effects were not detected for physician assessed pain (SMD: -0.14; 95% CI: -0.49 to 0.22, p=0.45) or Ritchie articular index (SMD: 0.15; 95% CI: -0.19 to 0.49, p=0.40) at 3-4 months. The results suggest that omega-3 PUFAs are an attractive adjunctive treatment for joint pain associated with rheumatoid arthritis, inflammatory bowel disease, and dysmenorrhea.
18985367 CD4(+)CD25 (+) regulatory T cells in human lupus erythematosus. 2009 Jan Natural CD4(+)CD25(+) regulatory T cells (T(reg)) show a potent immunosuppressive function and contribute to immunologic self-tolerance by suppressing potentially auto-reactive T cells. Depletion of these cells leads to the induction of severe autoimmune diseases in animal models; more recently, several studies have also reported an impairment of T(reg) number and/or function in various human autoimmune diseases. For example, aberrant numbers of circulating CD4(+)CD25(+) T(reg) have been seen in patients with type I diabetes, mycosis fungoides, graft-versus-host-reaction, and rheumatoid arthritis. Moreover, increased numbers of functionally active CD4(+)CD25(+) T(reg) have been detected in the synovial fluid of patients with rheumatoid arthritis. In systemic lupus erythematosus (SLE), conflicting data on the role of CD4(+)CD25(+) T(reg) in human autoimmune diseases have been presented in the literature. Decreased numbers of peripheral blood T(reg) have been reported by most studies on SLE patients with active disease, but non-impaired or even increased CD4(+)CD25(+) T(reg) numbers have also been described. In addition, both deficient and normal suppressive capacity of isolated T(reg) have been observed in SLE. Analysis of CD4(+)FoxP3(+) T(reg) in skin lesions of patients with a primarily cutaneous manifestation of the disease showed a significant reduction in cell numbers as compared to other inflammatory skin diseases, suggesting the importance of analyzing T(reg) numbers in the affected tissue. In this review, we discuss the role of CD4(+)CD25(+) T(reg) in autoimmunity and recent published data on SLE. Furthermore, we highlight the need for additional studies that address specific gaps of knowledge regarding the pathophysiological mechanisms as well as the identification of future therapeutic strategies for autoimmune diseases.
16881098 Magnetic resonance imaging is more sensitive than radiographs in detecting change in size 2006 Oct OBJECTIVE: To evaluate the technological performance of magnetic resonance imaging (MRI) with respect to projection radiography by determining the incidence of changes in the size of individual bone lesions in inflammatory arthritis, using serial high-resolution in-office MRI over short time intervals (8 months average followup), and by comparing the sensitivity of 3-view projection radiography with in-office MRI for detecting changes in size and number of individual erosions. METHODS: MR examinations of the wrists and second and third metacarpophalangeal joints were performed using a portable in-office MR system in a total of 405 patients with inflammatory arthritis, from one rheumatologist's practice, who were undergoing aggressive disease modifying antirheumatic drug therapy. Of the patients, 156 were imaged at least twice, allowing evaluation of 246 followup examinations (mean followup interval of 8 months over a 2-year period). Baseline and followup plain radiographs were obtained in 165 patient intervals. Patients refused radiographic examination on 81 followup visits. RESULTS: MRI demonstrated no detectable changes in 124 of the 246 (50%) followup MRI examinations. An increase in the size or number of erosions was demonstrated in 74 (30%) examinations, a decrease in the size or number of erosions in 36 (15%), and both increases and decreases in erosions were seen in 11 (4%). In the 165 studies with followup radiographic comparisons, only one examination (0.8%) showed an erosion not seen on the prior examination and one (0.8%) showed an increase in a previously noted erosion. CONCLUSION: We showed that high-resolution in-office MRI with an average followup of 8 months detects changes in bony disease in 50% of compliant patients during aggressive treatment for inflammatory arthritis in a single rheumatologist's office practice. Plain radiography is insensitive for detecting changes in bone erosions for this patient population in this time frame.
16611630 ADAMTS-12 associates with and degrades cartilage oligomeric matrix protein. 2006 Jun 9 Loss of articular cartilage because of extracellular matrix breakdown is the hallmark of arthritis. Degradative fragments of cartilage oligomeric matrix protein (COMP), a prominent noncollagenous matrix component in articular cartilage, have been observed in the cartilage, synovial fluid, and serum of arthritis patients. The molecular mechanism of COMP degradation and the enzyme(s) responsible for it, however, remain largely unknown. ADAMTS-12 (a disintegrin and metalloprotease with thrombospondin motifs) was shown to associate with COMP both in vitro and in vivo. ADAMTS-12 selectively binds to only the epidermal growth factor-like repeat domain of COMP of the four functional domains tested. The four C-terminal TSP-1-like repeats of ADAMTS-12 are shown to be necessary and sufficient for its interaction with COMP. Recombinant ADAMTS-12 is capable of digesting COMP in vitro. The COMP-degrading activity of ADAMTS-12 requires the presence of Zn2+ and appropriate pH (7.5-9.5), and the level of ADAMTS-12 in the cartilage and synovium of patients with both osteoarthritis and rheumatoid arthritis is significantly higher than in normal cartilage and synovium. Together, these findings indicate that ADAMTS-12 is a new COMP-interacting and -degrading enzyme and thus may play an important role in the COMP degradation in the initiation and progression of arthritis.
18525432 Medical skepticism and the use of complementary and alternative health care providers by p 2008 Jun BACKGROUND: Our understanding of the determinants of use of complementary and alternative (CAM) providers is limited, especially in regard to medical skepticism (ie, doubt in the ability of conventional medical care to appreciably alter health status). OBJECTIVES: To determine whether medical skepticism was associated with CAM provider use in patients with arthritis and to explore the association between medical skepticism and demographic and health-related characteristics of persons with arthritis. METHODS: A cross-sectional analysis of data from patients (N = 721) with osteoarthritis, rheumatoid arthritis, or fibromyalgia who completed a questionnaire about their health, health care use, and health-related attitudes/behaviors, including medical skepticism. Patients were recruited from 14 rheumatology practices in North Carolina. A multiple logistic regression analysis was conducted to examine the relationship between medical skepticism and the use of any CAM providers. Multiple linear regression analysis was conducted to examine relationships between medical skepticism and demographic and health-related measures. RESULTS: Fifteen percent of the sample used one or more CAM providers. Medical skepticism was positively associated with CAM provider use. A one point increase in skepticism increased the probability of CAM provider use by approximately 70% (odds ratios =1.70; 95% confidence intervals [1.13-2.56]). Individuals, who were younger, had better perceived health, and had a diagnosis of osteoarthritis or fibromyalgia had greater skepticism. CONCLUSIONS: By knowing more about medical skepticism and other determinants of CAM provider use, conventional practitioners can target patients to improve their uptake of appropriate conventional care, while also monitoring patients alternative therapy use.
18344925 Recommendations for the diagnosis and treatment of latent and active tuberculosis in infla 2008 Jan The Portuguese Society of Rheumatology and the Portuguese Society of Pulmonology have updated the guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (ATB) in patients with inflammatory joint diseases (IJD) that are candidates to therapy with tumour necrosis factor alpha (TNFalpha) antagonists. In order to reduce the risk of tuberculosis (TB) reactivation and the incidence of new infections, TB screening is recommended to be done as soon as possible, ideally at the moment of IJD diagnosis, and patient assessment repeated before starting anti-TNFalpha therapy. Treatment for ATB and LTBI must be done under the care of a TB specialist. When TB treatment is indicated, it should be completed prior to starting anti-TNFalpha therapy. If the IJD activity justifies the need for immediate treatment, anti-TNFalpha therapy can be started two months after antituberculous therapy has been initiated, in the case of ATB, and one month after in the case of LTBI. Chest X-ray is mandatory for all patients. If Gohn s complex is present, the patient should be treated for LTBI; healed lesions require the exclusion of ATB. In cases of suspected active lesions ATB should be excluded/confirmed and adequate therapy initiated. Tuberculin skin test, with two units of RT23, should be performed in all patients. If the induration is <5 mm, the test should be repeated within 1 to 2 weeks, on the opposite forearm, and will be considered negative only if the result is again <5 mm. Positive TST implicates LTBI treatment, unless previous proper treatment was provided. If TST is performed in immunossuppressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNFalpha therapy, even in the presence of a negative test, after risk/benefit assessment.
17117328 [Guidelines for the diagnosis and treatment of latent tuberculosis infection and active tu 2006 Sep The Portuguese Society of Rheumatology (SPR) and the Portuguese Society of Pulmonology (SPP) have developed guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (AT) in patients with inflammatory joint diseases (IJD), namely rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, treated with tumour necrosis factor alpha (TNF-a) antagonists. Due to the high risk of tuberculosis (TB) in patients with IJD, LTBI and AT screening should be performed as soon as possible, ideally at the moment of IJD diagnosis. Even if TB screening was performed at the beginning of the disease, the evaluation should be repeated before starting anti-TNF-a therapy. When TB (LTBI or AT) treatment is indicated, it should be performed before the beginning of anti-TNF-a therapy. If the IJD activity requires urgent anti-TNF-a therapy, these drugs can be started after two months of antituberculosis therapy in AT cases, or after one month in LTBI cases. Chest X-ray is mandatory for all patients. If abnormal, e.g. Gohn complex, the patient should be treated as LTBI; residual lesions require the exclusion of AT and patients with history of untreated or incomplete TB treatment should be treated as LTBI. In cases of suspected active lesions, AT diagnosis should be confirmed and adequate therapy initiated. Tuberculin skin test (TST), with two units of RT23, should be performed in all patients. If induration is less than 5 mm, the test should be repeated after 1 to 2 weeks, on the opposite forearm, and should be considered negative if the result is again inferior to 5 mm. Positive TST implicates LTBI treatment. If TST is performed in immunosuppressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNF-a therapy, even in the presence of a negative test.
17668585 [Complications of distal tubular acidosis in primary Sjögren's syndrome]. 2007 Mar Renal involvement in primary Sjögren's syndrome occurs in 10-60% of cases. Tubulointerstitial nephritis with distal renal tubular acidosis (DRTA) is the main type of involvement. It's generally asymptomatic and revealed by complications of DRTA. We report 4 cases of GJS complicated by nephrocalcinosis, tetapresic hypokaliemia and osteomalacia. In 2 cases, nephrocalcinosis was diagnosed simultaneously with the GJS. The 2 other cases were diagnosed 3 and 15 years after primary GJS. All patients were treated by coticosteroids at the dose of 0.5 mg/Kg/jour, alkaline solution, K Cl in 2 cases and vitamin D in 2 cases. After a mean follow up of 8.7 years, the renal function remain stable in the 3 cases of nephrocalcinosis and in a patient with osteomalacia, bone lesions progressed. In conclusion, DRTA must be detected by acidification tests in patients with primary Sjögren's syndrome because of their latency and to prevent severe complications.
16970979 Granulomatous hepatitis and Sjogren's syndrome: an association. 2006 Dec BACKGROUND: Sjogren's syndrome (SS) is a common autoimmune disorder in which liver involvement is frequent, but generally mild and subclinical. Multiple hepatic histologies have been reported, but to our knowledge an association with granulomatous hepatitis (GH) has never been described. We recently evaluated an individual in whom biopsy-proven GH was associated with concomitant SS. OBJECTIVE: To clarify the possible association between GH and SS. METHODS: We retrospectively reviewed all cases of biopsy-proven GH seen in our institution from 1991 to 2004. Overall, there were 16 individuals with GH identified of which 4 were considered idiopathic in origin. These individuals underwent an extensive evaluation for the presence of SS as well as other disorders known to be associated with GH. RESULTS: Of the 4 identified cases with a previously suspected idiopathic GH, 3 met criteria for primary SS. All 3 individuals underwent minor salivary gland biopsy, which was diagnostic for this condition. CONCLUSIONS: These results suggest a likely association between these 2 conditions. Further epidemiological studies will be necessary to confirm this finding.
16844955 Intravenous immunoglobulin treatment in painful sensory neuropathy without sensory ataxia 2006 Aug Patients having neuropathy associated with Sjögren's syndrome may present with pain and superficial sensory involvement in the absence of sensory ataxia. Treatment for this form of associated neuropathy has not been established. The case of a patient with painful sensory neuropathy associated with Sjögren's syndrome, whose symptoms, particularly pain, responded well to intravenous immunoglobulin both at onset and in a relapse, is reported. Other patients with painful sensory neuropathy associated with Sjögren's syndrome may also be candidates for intravenous Ig treatment.
19087701 [Establishment of Sjögren's syndrome models by immunization with alpha-Fodrin: experiment 2008 Aug 26 OBJECTIVE: To explore the possibility to establish Sjögren's syndrome models by immunizing mice with alpha-fodrin. METHODS: Twenty-four 4-week-old BALB/C mice were randomly divided into 4 equal groups to undergo subcutaneous injection of alpha-Fodrin, submaxillary gland homogenate and glutathione S-transferase (GST) or phosphate-buffered saline (PBS) (negative control groups) on days 0, 14, 35, and 56 respectively. The drinking amount of water was measured. Blood samples were collected every 2 - 3 weeks. Munofluorescence assays and ELISA were used to examine the presence of anti-Fodrin, anti-type 3 muscarinic acetylcholine receptor polypeptide (M3RP), anti-SSA, anti-SSB, rheumatoid factor (RF), and antinuclear antibody (ANA). Immunochemistry was used to detect the levels of interferon (IFN)-gamma, interleukin (IL)-2, and IL-10. One mouse was killed from each group every 2 - 3 weeks. The salivary glands were examined. RESULTS: (1) No auto-immune antibody was found in the serum samples of the mice before immunization. Antibodies against alpha-Fodrin and M2RP, and ANA were positive in the serum samples of the alpha-Fodrin and submaxillary gland homogenate groups since the 35th day after immunization, and were all negative in the 2 control groups. However, no antibodies against SSA, SSB and RF were found in all 4 groups. (2) Lymphocytic infiltration could be seen in the salivary glands of the immunized animals since 50th days after the first immunization of alpha-Fodrin and submaxillary gland homogenate. Immunohistochemistry showed alpha-Fodrin expression in the submaxillary glands of the alpha-Fodrin and submaxillary gland homogenate groups, but not in the PBS and GST controls. (3) The serum IFN-alpha levels of the alpha-Fodrin and submaxillary gland homogenate groups were (81.6 +/- 7.1) and (90.5 +/- 4.9) pg/ml respectively, both significantly higher than those of the GST and PBS groups [(30.1 +/- 5.9) and (19.3 +/- 6.4) pg/ml respectively, both P < 0.05]. The serum IL-2 levels of the alpha-Fodrin and submaxillary gland homogenate groups were (18.7 +/- 2.3) and (19.8 +/- 0.9) pg/ml respectively, both significantly higher than those of the GST and PBS groups [(4.9 +/- 1.1) and (3.5 +/- 1.6) pg/ml respectively, both P < 0.05]. No difference was found in the level of serum IL-10 among the 4 groups. (4) There was no significant difference in the volume of water volume drunk among the 4 groups. CONCLUSION: (1) It is possible to establish mouse mice SS models by immunization with alpha-Fodrin or submaxillary gland homogenate that are reminiscent of human SS. (2) The appearance of multiple antibodies may be related to the antigen epitope spreading. (3) The pathogenesis of SS may be related to Th1 type response.
19080074 [Diagnostic value of anti-alpha-fodrin antibody testing for Sjögren's syndrome: a meta-an 2008 Nov 18 OBJECTIVE: To evaluate the diagnostic accuracy of anti-alpha-fodrin antibody for Sjögren's syndrome (SS). METHODS: Qualified literatures on evaluation of anti-alpha-fodrin antibody in diagnosis of SS in English and Chinese published between January 1997 and December 2007 were retrieved from the Cochrane Library, Medline, Embase, and China National Knowledge Infrastructure (CNKI) databases, etc. Two reviewers independently assessed the methodological quality of each study with the tool QUADAS (quality assessment of diagnostic accuracy studies). Statistical analysis was performed by employing MATLAB, Review Manager 4.2 and Meta-Disc1.4. A meta-analysis of the reported sensitivity and specificity of each study and Summary Receiver Operating Characteristic (SROC) curve was performed. RESULTS: Eighteen literatures were included at last. After testing the heterogeneity of the included articles, proper effect model was selected to calculate the pooled weighted sensitivity and specificity with 95% confidence interval: for anti-alpha-fodrin antibody IgG, the sensitivity was 0.40 [95%CI (0.37-0.43)] and the specificity was 0.82 [95%CI (0.79-0.84)], the area under the curve (AUC) of SROC was 0.8029 (SE=0.0580). Eight studies tested anti-alpha-fodrin antibody IgA, the pooled weighted sensitivity and specificity with 95% confidence interval were 0.34 [95%CI (0.30-0.38)] and 0.83 [95%CI (0.79-0.86)] respectively, the AUC of SROC was 0.6374 (SE=0.1841), the synthesis data all showed heterogeneity. The subgroups were analyzed to identify the sources of heterogeneity according to age, race, assay method, agent source, diagnostic criteria, and country. There was homogeneity among the 4 studies from China, and the 6 studies from Japan, the AUC of SROC were 0.7343 (SE=0.0448) and 0.9273 (SE=0.0394), respectively. CONCLUSION: Diagnostic criteria, agent source, assay method, age, race, and country are the important sources of heterogeneity. Anti-alpha-fodrin antibodies IgG and IgA have relatively low pooled sensitivity and relatively high pooled specificity. Negative anti-alpha-fodrin antibody has not important value in excluding SS, but positive anti-alpha-fodrin antibody may be a useful parameter in clinical diagnosis of SS.
18982854 Xerostomia: recognition and management. 2008 Sep Awareness and recognition of xerostomia are essential in order to help patients minimize dryness symptoms, to institute preventive measures and to limit oral complications. The dental professional has the opportunity to ask every patient if they are experiencing dry mouth. In particular, complaints of dryness while eating, or difficulty swallowing dry foods, or the necessity of using liquids to ease swallowing are important clues that salivary function may be impaired. As part of a routine oral examination, one should examine the oral cavity carefully for signs of salivary gland dysfunction. Findings such as an increase in caries activity, mucosal alterations, infection or salivary gland enlargement may indicate salivary dysfunction. Evaluation should be conducted proactively at each patient visit. Early recognition will minimize damage and dysfunction and allow appropriate management to begin. Although the salivary dysfunction may be irreversible, preventive measures and conservative treatments can avoid or limit mucosal breakdown, infections and permanent damage to teeth. Adequate symptomatic relief is possible with local palliative and systemic measures in many patients. Appropriate management of symptoms and increasing saliva output may help patients feel more comfortable and improve their quality of life.