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ID PMID Title PublicationDate abstract
18261277 [High-dose immunosuppression and autologous peripheral blood stem cell transplantation for 2007 Nov OBJECTIVES: To assess the safety and efficacy of high-dose immunosuppression and autologous peripheral blood cell transplantation (APBSCT) in severe and refractory primary Sjögren's syndrome (pSS) and to analyze immune reconstitution in pSS. METHODS: Two patients with severe and refractory primary pSS were included in this study. They suffered still with active pSS despite the use of prednisone and immunosuppression agents. A regimen of high-dose immunosuppression and APBSCT was carried out for them. Dynamic T cell subgroup was tested with flow cytometry before and after PBSCT and the diversity of T cell receptor repertoire and CDR3 spectrum with RT-PCR and genescan. RESULTS: Both of the pSS cases underwent PBSCT smoothly. Clinical assessments showed improvement. Immune reconstruction lagged behind hematopoietic reconstitution. The skew of T cell receptor repertoire was somewhat corrected and CDR3 spectrum changed from oligoclonality to poly-clonality. CONCLUSION: High dose chemotherapy (HDC) and APBSCT are feasible and safe and can result in short-term or middle-term improvement of disease in patients with severe pSS which is refractory to conventional treatment. It is observed in this study that immune reconstruction recovered 3 moths after the treatment. Long-term efficacy of HDC + PBSCT in pSS should be studied in large number of cases with follow up of longer time.
17922736 Nodular pulmonary amyloidosis and Sjögren's syndrome in a patient treated with intermitte 2007 Oct In the available literature, we have found the descriptions of 5 cases of nodular pulmonary amyloidosis associated with Sjögren's syndrome. In our practice, such a case has occurred in a patient with chronic renal failure. A 53-year-old woman underwent nephrological, rheumatological, and pulmonological examinations because of end-stage renal disease with a small cirrhotic kidney in renal ultrasound examination, pulmonary nodules, and xerophthalmia. Serological data revealed a slightly positive rheumatoid factor, antinuclear antibodies, anti-SS-A, anti-SS-B, and anti-RNP/Sm antibodies. Schirmer's test was positive on both sides and Sjögren's syndrome was recognized. Pulmonological examinations (the chest radiograph and CT scan, bronchofiberoscopy, culture of bronchial washings, bronchial biopsy, pleural effusion analysis, and a thick-needle biopsy) failed to determine the etiology of nodular changes in lungs. Immunofluorescence studies in the skin biopsy specimen showed IgM-positive staining. After 2 years of treatment with IHD, a toracoscopy was performed with enucleation of the nodules from the right lung. Histological examination showed massive deposits of amyloid, which allowed for a diagnosis of diffusive nodular pulmonary amyloidosis.
17403303 [Correlation of anti-60000 SSA antibody and anti-52000 SSA antibody with systemic lupus er 2007 Jan 2 OBJECTIVE: To investigate the correlation of anti-60 000 SSA antibody and anti-52 000 SSA antibody with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). METHODS: Western blotting against purified 60 000 SSA antigenic polypeptide and 52 000 SSA antigenic polypeptide were done to detect the anti-60 000 SSA and anti-52 000 SSA antibodies in 59 serum samples positive in anti-SSA antibodies, among which 44 samples were from SLE patients and 15 samples from SS patients. RESULT: There was no significant difference in positive rate of anti-60 000 SSA antibodies between the SLE and pSS patients (P > 0.05). But the sole positive rate of anti-60 000 SSA antibodies of the SLA patients was 39.47% (15/38), significantly higher than that of the primary SS (pSS) patients ((6.67%, 1/15, P < 0.05). The positive rate of anti-52 000 SSA antibodies of the pSS patients was 93.33% (14/15), significantly higher than that of the SLE patients (23/38, 60.53%, P < 0.05). There was no significant differences in positive rates of anti-60 000 SSA antibodies and anti-52 000 SSA antibodies between the secondary SS (sSS) and pSS patients (P > 0.05). CONCLUSION: The pSS patients mainly present anti-52 000 antibodies and with a very low sole anti-60 000 SSA antibody positive rate. Sole positivity of anti-52 000 SSA antibodies maybe correlated with pSS and is not a strong implication for the diagnosis of sSS. Sole positive anti-60000 SSA antibodies rate can be seen mainly in SLE.
17225057 Orofacial dystonia related to Sjogren's syndrome. 2007 Oct Sjogren's syndrome (SS), either primary or secondary, is rarely accompanied by CNS complications. We report the exceptional case of a patient with secondary SS, who presented orofacial dystonia as a consequence of her disease. Initial treatment with clonazepam and levetiracetam was unsuccessful. However, dystonia was dramatically improved by a treatment with corticosteroids. This case demonstrates that corticosteroids can be efficacious in the treatment of dystonia related to SS.
17221146 Efficacy prediction of cevimeline in patients with Sjögren's syndrome. 2007 Aug The objective of this study was to examine the clinical and immunological factors influencing the efficacy of cevimeline hydrochloride hydrate (cevimeline) for the treatment of xerostomia in patients with Sjögren's syndrome (SS). Thirty primary SS patients who were medicated with cevimeline were enrolled in this study. Whole stimulated sialometry (WSS) was compared between pre- and posttreatment points (4 weeks after oral cevimeline administration) and the increment rate of WSS was calculated. Multiple regression was employed to examine the relative contributions of the clinical and immunological factors, including age, pretreatment WSS, duration of disease, sialography, minor salivary gland biopsy, anti-Ro/SS-A antibodies, anti-La/SS-B antibodies, and antibodies to muscarinic type 3 receptors to the posttreatment WSS. Patients with normal sialography findings, negative minor salivary gland biopsy, and absence of anti-La/SS-B antibodies had significantly higher increment rates of WSS compared with those with positive findings (p=0.042, 0.002, and 0.018, respectively). Results of the multiple regression analysis showed that sialography (coefficient=-0.867, p=0.004) and minor salivary gland biopsy (coefficient=-0.869, p=0.003) had significant associations with the posttreatment WSS. Our preliminary results demonstrated the relationship between the effect of cevimeline on saliva secretion and the degree of salivary gland destruction evaluated by sialography and histopathological findings in the labial minor salivary glands. These diagnostic approaches could provide useful prognostic information on the efficacy of cevimeline in SS patients.
17207041 Thymic and pulmonary mucosa-associated lymphoid tissue lymphomas in a patient with Sjögre 2007 Jan Mucosa-associated lymphoid tissue lymphoma (MALToma) has been reported in several organs. Among MALTomas, thymic and pulmonary MALTomas are rare. The present report describes a patient with Sjögren's syndrome who presented thymic and pulmonary MALTomas. Although the exact pathogenetic relationship between these two tumours is uncertain, it is likely that the underlying immune dysregulation related to Sjögren's syndrome contributed to the occurrence and the unusual manifestation of MALTomas in this patient.
17101831 Peripheral neuropathy in primary sjogren syndrome: a population-based study. 2006 Nov BACKGROUND: Neurological manifestations appear to be frequently involved in patients with primary Sjögren syndrome (PSS). OBJECTIVE: To investigate the involvement of the peripheral nervous system, including small-diameter nerve fibers, in an unselected cohort of patients who fulfilled the new international criteria for PSS. DESIGN: Cross-sectional study. SETTING: Stavanger University Hospital. Patients Sixty-two patients with PSS (mean +/- SD age, 57.1 +/- 14.6 years). INTERVENTIONS: Clinical neurologic examinations, conventional nerve conduction studies, and skin punch biopsies. MAIN OUTCOME MEASURES: Signs of large-diameter and small-diameter peripheral nerve fiber neuropathy as determined by clinical examination, nerve conduction studies, and densities of intraepidermal nerve fibers in skin punch biopsy specimens. RESULTS: Seventeen patients (27%) were diagnosed as having neuropathy after clinical examination. The results of nerve conduction studies were abnormal in 34 patients (55%): 19 patients (31%) had motor neuropathy, 8 (13%) had sensory neuropathy, and 7 (11%) had sensorimotor neuropathy. Two patients had intraepidermal nerve fiber densities less than 3.4 fibers per millimeter, fitting the morphologic criteria for small-diameter nerve fiber neuropathy. CONCLUSIONS: Peripheral neuropathy occurs in a large proportion of patients with PSS, in most cases as a subclinical demyelinating neuropathy. Small-diameter nerve fiber neuropathy is not a frequent finding in these patients.
16996579 The overlap of Sjögren's syndrome with other systemic autoimmune diseases. 2007 Feb OBJECTIVE: To analyze the main diagnostic problems caused by the overlap between Sjögren's syndrome (SS) and other systemic autoimmune diseases (SAD). METHODS: We performed a MEDLINE search for articles published between January 1966 and December 2005 that specifically analyzed the overlap between SS and other SAD. We identified a list of diagnostic problems in patients with primary SS who had features considered typical of other SAD. RESULTS: Clinically, the main diagnostic problems occur in SS patients presenting with arthritis, Raynaud phenomenon, cutaneous features (subacute cutaneous lupus erythematosus, purpura, livedo reticularis, erythema nodosum), interstitial pulmonary disease, and cytopenias (leukopenia, thrombocytopenia). Immunologically, antiphospholipid antibodies (aPL) and antineutrophil cytoplasmic antibodies (ANCA) are the most frequent atypical autoantibodies found in primary SS, with a prevalence ranging between 10 and 20%. However, coexisting antiphospholipid syndrome or systemic vasculitis is only detected in around 10% of SS patients with aPL or ANCA. Anti-DNA and anticentromere antibodies have a prevalence of 5 to 10%, but are more closely related to clinical and/or laboratory data suggestive of associated systemic lupus erythematosus and limited systemic sclerosis, respectively, leading to the fulfillment of classification criteria for these diseases in more than 25% of cases. CONCLUSION: The wide variety of clinical and immunological manifestations of patients with primary SS often overlap with other SAD, making the differentiation between primary SS, SS associated with SAD, and SS-like presentations of some other SAD difficult. This overlap suggests that the current classification criteria are useful in differentiating between autoimmune and non-autoimmune processes but fail to clearly differentiate among SAD.
19035481 Interleukin-6 blockade suppresses autoimmune arthritis in mice by the inhibition of inflam 2008 Dec OBJECTIVE: To investigate the mechanism of interleukin-6 (IL-6) blockade in autoimmune arthritis, by comparing the effect of anti-IL-6 receptor (anti-IL-6R) monoclonal antibody (mAb) treatment with the effect of soluble tumor necrosis factor (sTNFR)-Fc fusion protein treatment on T helper cell differentiation in collagen-induced arthritis (CIA). METHODS: DBA/1 mice were immunized with type II collagen (CII) to induce arthritis and were left untreated or were treated with anti-IL-6R mAb or TNFR-Fc. T helper cell differentiation and cytokine expression during the development of arthritis in these mice were analyzed. RESULTS: Immunization with CII predominantly increased the frequency of Th17 cells rather than Th1 cells. The frequency of FoxP3+ Treg cells was also increased after immunization. Treatment of mice with CIA with anti-IL-6R mAb on day 0 markedly suppressed the induction of Th17 cells and arthritis development, but treatment with this antibody on day 14 failed to suppress both Th17 differentiation and arthritis. In contrast, treatment of mice with CIA with TNFR-Fc from day 0 to day 14 suppressed neither Th17 differentiation nor arthritis, but treatment from day 21 to day 35 successfully ameliorated arthritis without inhibiting Th17 induction. Neither antibody treatment increased the frequency of Treg cells. CONCLUSION: Our results indicate that the protective effect of IL-6 blockade, but not tumor necrosis factor (TNF) blockade, in CIA correlates with the inhibition of Th17 differentiation. Our findings suggest that IL-6 blockade in rheumatoid arthritis in human is also likely to involve a therapeutic mechanism distinct from that of TNF blockade and thus may represent an alternative therapy for patients in whom the disease is refractory to TNF blockade.
18582368 Induction of arthritis by high mobility group box chromosomal protein 1 is independent of 2008 INTRODUCTION: TNFalpha and high mobility group box chromosomal protein 1 (HMGB1) are two potent proinflammatory cytokines implicated as important mediators of arthritis. Increased levels of these cytokines are found in the joints of rheumatoid arthritis patients, and the cytokines trigger arthritis when applied into the joints of naïve mice. HMGB1 is actively released from immune cells in response to TNFalpha; once released, HMGB1 in turn induces production of several proinflammatory cytokines--including IL-6 and TNFalpha--by macrophages. Whether HMGB1-induced arthritis is mediated via the TNFalpha pathway, however, is unknown. The purpose of the present study was to investigate whether the arthritis-inducing effect of HMGB1 is dependent on TNFalpha expression in vivo and to assess whether TNFalpha deficiency affects a proinflammatory cytokine response to HMGB1 in vitro. METHODS: TNFalpha knockout mice and backcrossed control animals on a C57Bl6 background were injected intraarticularly with 5 microg HMGB1. Joints were dissected 3 days after intraarticular injection and were evaluated histologically by scoring the frequency and severity of arthritis. For in vitro studies, mouse spleen cultures from TNFalpha knockout mice and from control mice were incubated with different doses of HMGB1, and cell culture supernatants were collected at different time points for analysis of IL-6. RESULTS: Intraarticular injection of HMGB1 into healthy mouse joints resulted in an overall frequency of 32% to 39% arthritic animals. No significant differences were found with respect to the severity and incidence of synovitis between mice deficient for TNFalpha (seven out of 18 mice with arthritis) in comparison with control TNFalpha+/+ animals (six out of 19). No significant differences were detected between spleen cells from TNFalpha+/+ mice versus TNFalpha-/- mice regarding IL-6 production upon stimulation with highly purified HMGB1 after 24 hours and 48 hours. Upon stimulation with a suboptimal dose of recombinant HMGB1, however, the splenocytes from TNFalpha+/+ animals released significantly more IL-6 than cells from the knockout mice (602 +/- 112 pg/ml and 304 +/- 50 pg/ml, respectively; P < 0.05). CONCLUSION: Our data show that HMGB1-triggered joint inflammation is not mediated via the TNF pathway. Combined with our previous study, we suggest that HMGB1-triggered arthritis is probably mediated through IL-1 activation.
17983144 The assessment of T-cell apoptosis in synovial fluid. 2007 T-cell apoptosis is central to the resolution of chronic inflammation. Inhibition of this process of programmed cell death contributes to disease persistence in conditions such as rheumatoid arthritis. An understanding of T-cell apoptosis and its regulation is clearly important for understanding the pathophysiology of inflammatory disease. This chapter describes a number of apoptosis assays that can be used to measure T-cell apoptosis in synovial fluid. The choice of assay depends, in part, on the phase of apoptosis under investigation and this review puts this into context by introducing these phases and their regulation.
18197930 Tracheo-broncho-bronchiolar lesions in Sjögren's syndrome. 2008 Jan A 53-year-old woman reported having a persistent cough and bloody sputum. She did not smoke but had received a diagnosis of Sjögren's syndrome. Chest CT revealed middle lobe syndrome, bronchiectasis and diffuse centrilobular nodular lesions. Bronchoscopy displayed multiple whitish polypoid lesions protruding from the cartilage rings and tracheobronchopathia osteochondroplastica was histologically confirmed by the presence of bony tissue in the tracheo-bronchial wall. Video-assisted thoracoscopic biopsy demonstrated lymphocyte aggregation causing follicular broncho-bronchiolitis. Erythromycin therapy resulted in improvement of the follicular bronchiolitis but not the tracheobronchopathia osteochondroplastica.
17554985 [A case of primary Sjögren's syndrome complicated with lung adenocarcinoma]. 2007 May A 69-year-old woman presented with headache. Her chest radiograph and computed tomographic scans showed a mass shadow causing superior vena cava syndrome. Bronchofiberscopic examination was nonproductive. The serum value of carcinoembryonic antigen was highly elevated, so we made a presumed diagnosis of primary non-small lung cancer. She also complained of dry eyes and mouth. The elevated values of serum antibodies against SS-A and SS-B and further examinations resulted in a definitive diagnosis of primary Sjögren's syndrome. Chemotherapy was not effective and she died 14 months later. Autopsy revealed that the mass shadow was a primary lung adenocarcinoma. At the age of 66 she suffered a refractory pneumothorax and her pulmonary cysts or bullae were surgically resected. Those lesions had bullae, emphysema, and alveolar septae thickened by infiltration of lymphoplasmacytic cells. Because she had complained of xerostomia for the last few decades, we associated the cysts with Sjögren's syndrome. Thoracic CT scans at that time showed a nodule next to a cystic lesion. We raise a possibility that lung cancer might derive from cystic lesions associated with Sjögren's syndrome.
17039338 [Labial salivary gland biopsy in Sjögren's syndrome]. 2006 Nov In the majority of cases, autoimmune sialadenitis is a feature of Sjögren's syndrome. This systemic autoimmune disease is, therefore, clinically characterised by sicca symptoms such as xerostomia and keratoconjunctivitis sicca. Since autoimmune sialadenitis affects major as well as minor salivary glands, histopathological examination is almost always carried out using labial salivary gland biopsies. A positive histopathological result is determined as a focal lymphocytic sialadenitis with at least one aggregate of 50 or more lymphocytes and histiocytes per 4 mm2 of salivary gland tissue. As one out of four objective findings, focus scoring belongs to the classification criteria for Sjögren's syndrome according to the American-European consensus group.
18625944 Bilateral infusion pump implants as therapy for refractory corneal ulcers in a patient wit 2008 Jul Internal infusion pumps are implantable and programmable systems that have been widely used for years in the management of chronic pain. During the past few years, these devices have had an increasingly prominent role given the possibility of insulin infusions in patients with diabetes mellitus because they provide patients with higher autonomy in the management of their disease, despite the fact that they are expensive systems and require surgery for implantation. These features make internal infusion pumps a suitable therapeutic option for those patients who need to use artificial tears continuously because of severe dry eyes. We report a case of severe eye pain due to xerophthalmia in a patient with CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome who was treated with an implanted pump reservoir.
17992591 Sjögren's syndrome--study of autoantigens and autoantibodies. 2007 Jun The presence of autoantibodies is the hallmark of systemic autoimmune diseases. During the past 30 years, intense clinical and basic research have dissected the clinical value of autoantibodies in many autoimmune diseases and offered new insights into a better understanding of the molecular and functional properties of the targeted autoantigens. Unraveling the immunologic mechanisms underlying the autoimmune tissue injury, provided useful conclusions on the generation of autoantibodies and the perpetuation of the autoimmune response. Primary Sjögren's syndrome (pSS) is characterized by the presence of autoantibodies binding on a vast array of organ and non-organ specific autoantigens. The most common autoantibodies are those targeting the Ro/La RNP complex, and they serve as disease markers, as they are included in the European-American Diagnostic Criteria for pSS. Other autoantibodies are associated with particular disease manifestations, such as anti-centromere antibodies with Raynaud's phenomenon, anti-carbonic anhydrase II with distal renal tubular acidosis, anti-mitochondrial antibodies with liver pathology, and cryoglobulins with the evolution to non-Hodgkin's lymphoma. Finally, autoantibodies against autoantigens such as alpha- and beta-fodrin, islet cell autoantigen, poly(ADP)ribose polymerase (PARP), NuMA, Golgins, and NOR-90 are found in a subpopulation of SS patients without disease specificity, and their utility remains to be elucidated. In this review, the molecular and clinical characteristics (divided according to their clinical utility) of the autoantigens and autoantibodies associated with pSS are discussed.
17882942 [A forty-five-years-old woman suffered from Sjögren syndrome with progressive tetraparesi 2007 Aug We herein report the finding of a 45-year-old woman suffered from Sjögren syndrome with progressive tetraparesis, who later developed systemic muscle atrophy and respiratory failure with a one-year clinical history. Neurological examinations revealed progressive tetraparesis with absent deep tendon reflexes, whereas no upper motor neuron signs were observed. The motor and sensory nerve conduction velocity and sensory nerve action potential (SNAP) were both completely normal, but the prolongation of distal motor latency in the median nerve and a decrease in the compound muscle action potential (CMAP) amplitude were observed. We ascertained that a spontaneous discharge was detected in her upper and lower limbs on electromyography (EMG). Her neurological findings as well as the EMG findings closely correlated with those of motor neuron disease; however, she showed a motor paralytic bladder and also demonstrated a serum antibody reaction with 50 kDa spinal cord protein of the rat. A lumbar MR image showed an increased signal intensity of the cauda equina on a gadolinium-enhanced T1 weighted image. We consider the immune-mediated impairment of the motor nerve associated with Sjögren syndrome to be the cardinal pathogenesis of the present patient, even though treatment with oral corticosteroids did not ameliorate her symptoms.
17728368 Prevalence of endometriosis in women with systemic lupus erythematosus and Sjogren's syndr 2007 Endometriosis is associated with a number of immunologic alterations. It has been suggested that autoimmune disorders could be more frequent in patients with endometriosis. The aim of this study is to ascertain whether the prevalence of two well-known autoimmune diseases [systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS)] is increased in women with endometriosis. The clinical charts of four different populations assisted at the same hospital were manually revised: (i) SLE population (n = 120), (ii) SS (n = 22), (iii) endometriosis (n = 342) and (iv) control population (n = 501 consecutive unselected asymptomatic women). Among SLE women, the prevalence of endometriosis was 1.67% (2/120), similar to the 4.39% prevalence of the control group (22/501), the OR being 0.37 [95%CI 0.09-1.59]. Among SS women, the prevalence of endometriosis was 9.09 (2/22), also similar to the control group OR 2.17 [95%CI 0.48-9.90]. In the same way, when comparing endometriosis cases with asymptomatic women, similar frequencies of SLE (0.58% and 0.2%) and SS were found (0% and 0%). Women with endometriosis do not have an increased prevalence of SLE or SS.
17314496 Possible involvement of oxidative stress in salivary gland of patients with Sjogren's synd 2006 OBJECTIVE: To determine the involvement of oxidative stress in the salivary gland of patients with Sjogren's syndrome (SS). METHODS: Oxidative damage to the gland was measured by 8-hydroxy-2'-deoxyguanosine (8-OHdG) and hexanoyl-lysine (HEL) using the SS saliva. In addition, lactate dehydrogenase (LDH) and mitochondrial glutamic-oxaloacetic transaminase (m-GOT), both general markers for cell damage, were also analyzed. RESULTS: Increased levels of 8-OHdG and HEL were found in the saliva of SS patients, but not in that of patients with other salivary gland dysfunction or of healthy individuals. Levels of LDH and m-GOT were significantly correlated with 8-OHdG and HEL levels, respectively. Furthermore, the increased levels of 8-OHdG and HEL were also correlated in the SS saliva. CONCLUSION: These findings suggested the involvement of oxidative stress in glandular tissue destruction in SS. It was indicated that the detection of 8-OHdG and HEL in the saliva may become a useful tool for the diagnosis of SS.
17252265 Use of the European preliminary criteria, the Breiman-classification tree and the American 2007 Jun This study was conducted to assess the use of the European preliminary criteria, the Breiman-classification tree and the American-European criteria for diagnosis of primary Sjögren's Syndrome (pSS) in daily practice. A retrospective analysis of 17 consecutive patients with pSS (European criteria) was performed evaluating the application of the Schirmer test, semiquantitative sialoscintigraphy, immunologic tests, including rheumatoid factor, antinuclear antibodies, Sjögren's syndrome autoantibodies (SS-A, SS-B) and lip biopsy. Out of the 17 patients with pSS according to the European criteria, 15 patients fulfilled the classification tree (=88.2%), and 4 patients fulfilled the American-European criteria (=23.5%, P = 0.001). In the four patients fulfilling the American-European criteria, a positive result of the sialoscintigraphy was not crucial for the diagnosis according to these criteria. In conclusion, the American-European criteria are more stringent than the European preliminary criteria. We assume the role of sialoscintigraphy to be reduced when applying the American-European criteria.