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ID PMID Title PublicationDate abstract
9317084 Primary biliary cirrhosis associated with mixed type autoimmune hemolytic anemia and sicca 1997 Sep A case presenting with an unusual association of primary biliary cirrhosis and mixed type autoimmune hemolytic anemia plus sicca syndrome is described. The 49-yr-old female primary biliary cirrhosis patient had a confirmed sicca syndrome and presented with jaundice and life-threatening anemia. Laboratory tests revealed positive Coombs' test with coexisting cold and warm autoantibodies. She was successfully treated by blood transfusion with packed red cells lacking any red cell antigens corresponding to serum alloantibodies and pulse methylprednisolone therapy. The patient remained stable under maintenance treatment using oral steroids and ursodeoxycholic acid. This case is probably the first reported showing an association between primary biliary cirrhosis and mixed type autoimmune hemolytic anemia plus sicca syndrome and was probably induced by heterogenous and complicated autoimmune reactions.
10638776 Calcitriol-mediated hypercalcaemia and increased interleukins in a patient with sarcoid my 1999 In this report we describe a patient with Sjögren's syndrome (SS) and calcitriol-mediated hypercalcaemia. Initially, there was no clinical evidence of sarcoidosis. The patient had hypercalcaemia associated with increased calcitriol serum levels; circulating interleukin-6 and tumour necrosis factor alpha levels were also elevated. At the beginning, therapy with clodronate was effective in decreasing the serum calcium levels. However, the serum calcitriol decreased only after chloroquine treatment was added. After 2 years of therapy, the patient developed progressive and extensive muscle weakness. A muscle biopsy revealed a very prominent non-caseating granulomatous myopathy. Corticosteroid therapy was then instituted. Although both chloroquine and corticosteroid therapy were associated with decreased serum interleukin and calcitriol levels, only corticosteroid therapy was effective in treating the sarcoid myopathy. The role of cytokines in calcitriol mediated hypercalcaemia is discussed.
10438965 Preferential localization of CD8+ alpha E beta 7+ T cells around acinar epithelial cells w 1999 Aug 15 The T lymphocytes that infiltrate the exocrine glands in Sjögren's syndrome (SS) play a key role in damaging glandular epithelial cells, but the mechanisms of this damage by T lymphocytes are not fully understood. To determine the cellular basis of this phenomenon, we focused our attention on the T lymphocytes around acinar epithelial cells in SS. We showed that CD8+ but not CD4+ T lymphocytes were located around the acinar epithelial cells and that a majority of these CD8+ T lymphocytes possess an unique integrin, alpha E beta 7 (CD103). The acinar epithelial cell adherent with alpha E beta 7 (CD103)+ CD8+ T lymphocytes was apoptotic. Both the perforin/granzyme B and Fas/Fas ligand pathways were implicated in the process of programmed cell death in lacrimal glands. These results suggested that alpha E beta 7 integrin, by interacting with E-cadherin, mediates the adhesion between CD8+ T lymphocytes and acinar epithelial cells in SS and participates in inducing epithelial cell apoptosis, leading to secretory dysfunction of exocrine glands, a hallmark of SS.
9129040 Ongoing Ig gene hypermutation in salivary gland mucosa-associated lymphoid tissue-type lym 1997 May 1 Salivary gland mucosa-associated lymphoid tissue (MALT) type lymphomas are typically indolent B-cell neoplasms that are often associated with Sjogren's syndrome. To better define the cell of origin and evaluate whether antigen receptor stimulation may be playing a role in tumor growth, the Ig heavy and light chain variable genes (VH and VL) expressed by five salivary gland MALT lymphomas were cloned and sequenced. Comparison to known germline sequences indicated that three of the lymphoma VH genes were derived from 51p1, a member of the VH1 family, while the other two used different VH gene segments from the VH3 family, 22-2B and HG19. All five of the VL genes belonged to the VkIII family, with three derived from Humkv325 and the other two from the Vg and Humkv328 genes. Numerous point mutations relative to the proposed germline genes were present in all of the lymphoma VH and VL genes. In addition, the VH and VL genes from each lymphoma showed intraclonal sequence heterogeneity indicative of ongoing somatic hypermutation. Because the process of Ig gene hypermutation is thought to occur at the germinal center stage of B-cell development, these findings suggest the MALT lymphoma cell of origin may be a germinal center B cell. Selection against mutations that result in replacement of amino acids suggested that Ig stimulation may be important for lymphoma growth. The possibility that antigen receptor stimulation may be involved in the growth of salivary gland MALT lymphomas is further suggested by the noted restricted use of VH and VL gene segments.
9229086 An outcome analysis of 100 women after explantation of silicone gel breast implants. 1997 Jul A prospective outcome analysis was conducted on 100 consecutive women who requested explantation of their silicone gel breast implants from January 6, 1992 (the moratorium), through 1995. Eighteen patients were referred by rheumatologists with a diagnosis of autoimmune or rheumatic disease. Six had autoimmune disease (systemic lupus, 2 patients; rheumatoid arthritis, 2 patients; multiple sclerosis, 1 patient; and Raynaud's disease, 1 patient). Twelve had rheumatic disease (fibromyalgia, 10 patients; inflammatory arthritis, 2 patients). All of these 18 patients had developed symptoms of their disease after they had received implants. All 100 patients were extensively evaluated pre- and postoperatively by interviews, clinical assessment, and by assay of the following laboratory tests: rheumatoid factor, ESR, ANA, and anti-Ro/SSA, -La/SSP, -Sm, -RNP, -double-stranded deoxyribonucleic acid, -Scl-70, -centromere, and -cardiolipin. Patients were also evaluated by a questionnaire that was sent at a mean time of 2.7 years postexplantation (range, 1-5 years), which had a 75% response rate. Reasons for implants were augmentation, 75%; lifting, 11%; reconstruction, 12%; and congenital aplasia, 2%. The mean age at first implant was 28.9 years (range, 13-55 years) and at explantation was 41.5 years (range, 25-65 years). The mean duration of implantation was 12.0 years (range, 1-27 years). Thirty-six percent of the patients had undergone at least one closed capsulotomy and 54% at least one open capsulotomy. The mean reasons for explantation were suspected silicone-related health problems, 76%; suspected rupture, 59%; breast firmness, 36%; breast pain, 36%; and musculoskeletal pain, 23%. Before explantation 75% of the questionnaire respondees had lost some sensitivity in their nipples following their breast augmentation. In 36% of those 75 patients, that loss was almost complete. Loss of sensitivity was related to capsular contracture and to pain (p < 0.05). Following explantation there was significant improvement in nipple sensitivity in 38% of breasts in the 75 respondees. A total of 186 implants were removed. Fifty-seven percent had failed by rupturing or leaking. Only 3.2% demonstrated extravasation extracapsularly. Twenty-five percent of the capsules were calcified, demonstrating visible plaques of calcification on their inner surface. Forty-two percent were colonized by bacteria. The prevalence of class III-IV capsular contracture was 61% and it was related to implant location, duration in situ, and capsular calcification (p < 0.05), but not to capsular colonization or implant integrity (p > 0.05). Only 43 of the 100 patients elected to have saline implants inserted. Of the others, 56% felt that the shell of the saline implant could be associated with medical problems. The others felt that breast size was of minor importance to them at this time. There were few complications from the explantation procedure. Two "masses" were discovered-one was an occult carcinoma, the other a galactocele. There was one wound infection, which responded to antibiotics. Three patients developed decreased sensitivity and 3 developed increased breast pain. From the patient questionnaires, in those women who did not have saline implants inserted, 15% felt that their breast appearance was improved after explantation, 36% were "pleased," 33% were disappointed, and 13% felt "mutilated". In women who did have saline implants inserted, 18% felt that their breast appearance was now improved, 60% were "pleased," and 14% were disappointed, mainly because of wrinkling. At a mean time of 2.7 years (range, 1-5 years) after explantation, 45% of the 75 questionnaire respondees felt that their implants had caused permanent health problems and 56% felt that they had not been given adequate informed consent by their original surgeon (particularly regarding implant rupture and a possible relationship to medical disease). (ABSTRACT TRUNCATED)
9788887 Nitric oxide as an inflammatory mediator in autoimmune MRL-lpr/lpr mice. 1998 Oct Nitric oxide (.NO) may exhibit proinflammatory features. .NO synthase type 2 (NOS2) is overexpressed and .NO overproduced in rodent models of induced inflammation. Blockage of .NO production by administration of NOS inhibitors prevents or reduces various types of induced inflammation in mice and rats. We have shown that autoimmune MRL-lpr/lpr mice overexpress NOS2 and overproduce .NO in an age-dependent fashion that parallels expression of arthritis, glomerulonephritis, and vasculitis. Blocking .NO production by oral administration of the NOS inhibitor NG-monomethyl-L-arginine reduced the arthritis, glomerulonephritis, and vasculitis, but it did not modify serum anti-DNA antibody levels or glomerular deposition of immune complexes. When mice with genetically disrupted NOS2 were backcrossed to MRL-lpr/lpr mice, the resultant (-/-) mice expressed no NOS2 and produced no .NO, the wild-type (+/+) mice overexpressed NOS2 and overproduced .NO (in comparison to normal, control mice), and the heterozygous (+/-) mice expressed and produced intermediate levels. Nephritis and arthritis in the (-/-) mice were comparable to that in MRL-lpr/lpr mice, but vasculitis was markedly decreased. Levels of anti-DNA antibodies were comparable in all mice, but IgG rheumatoid factor production was markedly reduced in the (-/-) mice. These results of studies in MRL-lpr/lpr mice with genetically disrupted NOS2 highlight the heterogeneity and complexity of the role of NOS2 and .NO in inflammation.
11602464 Lymphomas complicating Sjögren's syndrome and hepatitis C virus infection may share a com 2001 Nov BACKGROUND: The occurrence of B cell non-Hodgkin's lymphoma is a complication of Sjögren's syndrome (SS) and, at least in some countries, of chronic hepatitis C virus (HCV) infection. Lymphomas occurring in both diseases share a number of characteristics: predominance of low grade, marginal zone histological type, frequency of mucosal localisation, possible transformation into a large B cell lymphoma, association with asymptomatic low level cryoglobulinaemia, absence of virus within lymphoma cells, but localisation of lymphomas in organs where the chronic viral infection is active in patients with HCV and where the autoimmune disease is active in patients with SS. HYPOTHESIS: It is proposed that in both diseases the first event of lymphomagenesis is the chronic stimulation at the site of the disease of polyclonal B cells secreting rheumatoid factor (RF). Then, that these RF B cells may become monoclonal and disseminate in other organs. The monoclonal secreted RF complexed with polyclonal IgG may cryoprecipitate. The following step would be a chromosomal abnormality (for example, trisomy 3 or bcl-2 translocation) which would confer to these cells a low grade B cell lymphoma comportment. A last event (for example, a mutation of p53) might transform this low grade B cell lymphoma into a high grade, large B cell lymphoma. The non-random utilisation of VH and VL by SS associated lymphoma B cells and the recent demonstration that these lymphoma B cells may display RF activity support the hypothesis that these lymphomas grow through an autoantigen driven process. CONCLUSION: The best preventive treatment of lymphoproliferations occurring in SS probably consists in decreasing the hyperactivation of autoreactive B cells when it is present, allowing the use of immunosuppressive drugs such as methotrexate or even tumour necrosis factor alpha antagonists, which in theory could favour other types of lymphoproliferation.
10414856 Cytokine expression in human labial minor salivary gland epithelial cells in health and di 1999 May Microdissection of biopsy material from labial minor salivary glands followed by RT-PCR demonstrates extensive production of cytokines IL-2, 1L-6, IL-10, TNF-alpha, TGF-beta, and IFN-gamma in both normal glands and in glands affected by Sjögren's syndrome. Continuation of these studies should expand our knowledge of normal salivary gland function and the pathogenesis of Sjögren's syndrome.
9676778 Anti-centromere autoantibody in a patient evolving from a lupus/Sjögren's overlap to the 1998 Jul We characterized the development of the anti-centromere antibody in a patient prior to the development of CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias) symptoms. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblotting (IgG and IgM) of cellular extracts enriched for centromere antigens and indirect immunofluorescence were used to study the anti-centromere immune response. The sera recognized 3 centromere antigens with molecular masses 18,000 (CENP-A), 50,000 (CENP-D), and 80,000 (CENP-B). For CENP-A, IgM was present before the appearance of the IgG response. Anti-CENP-D revealed an IgM response that decreased over time but no IgG, while CENP-B showed an IgG response that strengthened and then weakened over time. The appearance of an anti-centromere nuclear fluorescence pattern correlated with the appearance of IgG anti-CENP-A. Signs and symptoms typical of CREST began about 4 years after antibodies to centromere antigens were found. The development of the CREST syndrome in our patient was preceded by the appearance of anti-centromere autoantibodies. For at least one of the antigens (CENP-A), there was an immunoglobulin class switch from IgM to IgG.
9588746 Polymorphisms of HLA class II genes and autoimmune responses to Ro/SS-A-La/SS-B among Japa 1998 May OBJECTIVE: To investigate HLA class II allele associations with autoantibody responses to Ro/SS-A and La/SS-B among Japanese subjects. METHODS: Haplotype and allele distributions, along with molecular polymorphisms, of HLA class II genes were analyzed by polymerase chain reaction-restriction fragment length polymorphism in 41 Japanese women with precipitating autoantibodies to Ro/SS-A and/or La/SS-B. RESULTS: Among women with both Ro/SS-A and La/SS-B antibodies, the HLA class II haplotype DRB1*08032/DQA1*0103/DQB1*0601 and DRB1*08032 allele showed significantly increased frequencies compared with patients with anti-Ro/SS-A alone or with normal controls. All women with both anti-Ro/SS-A and anti-La/SS-B, but not those with anti-Ro/SS-A alone, carried DRB1 alleles that shared the same amino acid residues at positions 14-31 and 71 of the hypervariable regions of the DRB1 chain. All anti-Ro/SS-A positive women carried 1 or 2 alleles of DQB1*06 and DQB1*03 subtypes that shared the same amino acid residues at positions 71-77 of the DQB1 chain. HLA class II allele distributions did not differ among 3 anti-Ro/SS-A positive groups with different disease expressions, i.e., patients with systemic lupus erythematosus, patients with primary Sjögren's syndrome, and women with no apparent symptoms of rheumatic disease. CONCLUSION: HLA class II allele distributions differ among anti-Ro/SS-A positive subjects according to the presence or absence of coexisting anti-La/SS-B antibodies, but not according to disease expression. Our findings suggest that different HLA class II molecules might control the development of anti-Ro/SS-A and/or anti-La/SS-B antibodies in the autoimmune response to the Ro/SS-A-La/SS-B complex.
9128423 [Primary biliary cirrhosis (PBC)-CREST overlap syndrome complicated with Sjögren's syndro 1997 Feb We reported two sisters of primary biliary cirrhosis (PBC)-CREST overlap syndrome complicated with Sjögren's syndrome (SS). Both patients had Raynaud's phenomenon, sclerodactylia, telangiectasia, chronic sialoadenitis, chronic nonsuppurative destructive cholangitis by liver biopsy and were positive for anti-centromere antibodies. This is the first report of two sisters of PBC-CREST overlap syndrome complicated with SS.
10782819 Increased serum levels of interleukin 10 in Sjögren's syndrome; correlation with increase 2000 Apr OBJECTIVE: To determine levels of interleukin 10 (IL-10) and IgG subclasses in serum from 53 patients with primary Sjögren's syndrome (SS). METHODS: Serum levels of IL-10 were measured using specific sandwich ELISA in 25 patients with "definite" SS, 28 with "possible" SS, and 32 healthy controls. Interferon-gamma (IFN-gamma) and transforming growth factor-beta1 (TGF-beta1) were also measured by immunoassays. Immunoglobulin classes, IgG subclasses, and C-reactive protein were measured by nephelometry. RESULTS: Circulating IL-10 was elevated in 25 patients. The increase reached significance in the group with possible SS (p = 0.03) versus controls. In the group with definite SS, IL-10 level was correlated with IgG1 level (p = 0.01, r = 0.67) and with focus score (p = 0.01). IFN-gamma was undetectable in most patients. TGF-beta1 was higher (not significantly) in possible SS than in definite SS. CONCLUSION: IL-10 is increased in SS and may account for the overproduction of IgG1 in the syndrome. High IL-10 in the absence of increased IgG1 in possible SS suggests that IL-10 may be necessary but not sufficient for IgG1 overproduction and that other factors are involved. Whereas the correlation of IL-10 level with focus score was expected, it is intriguing that IL-10 was more frequently increased in the incomplete (possible) form of SS than the complete (definite) form. Elevated IL-10 may characterize the lower stage of eccrine dysfunction and perhaps contributes to limiting its severity.
10673785 Immunohistochemical detection of insulin-like growth factor-I in the labial salivary gland 2000 Jan OBJECTIVE: The purpose of the present study was to investigate the presence of insulin-like growth factor-I (IGF-I) in the labial salivary glands of patients with Sjögren's syndrome and healthy controls and to determine if there are any differences between these two groups. DESIGN: An immunohistochemical study. SUBJECTS AND METHODS: Twenty-five patients with Sjögren's syndrome, 20 healthy controls and 20 patients with mucoceles of the lip were used in this study. All individuals underwent a systemic evaluation and a lip biopsy. Sections from the lip biopsies were stained with haematoxylin and eosin (H&E). Immunohistochemical staining was also performed using a three-step indirect immunoperoxidase for IGF-I. RESULTS: The light microscopic examination revealed the presence of a mononuclear infiltration in the labial salivary glands of patients with Sjögren's syndrome. Most of the infiltrates were lymphocytes. Immunohistochemically an intense staining result was apparent in the same group. In contrast sections of labial salivary glands of healthy individuals and of patients with mucoceles revealed very weak staining. CONCLUSIONS: The above findings and the fact that both lymphocytic infiltration and IGF-I were predominantly seen in ductal regions, suggest that IGF-I may be a target of autoimmunity in Sjögren's syndrome.
10958177 Disproportion of helper T cell subsets in peripheral blood of patients with primary Sjögr 2000 We studied the proportions of Th1 and Th2 cells in peripheral blood of 15 patients with primary Sjögren's syndrome (p-SS), by using a procedure to enumerate the cells synthesizing cytokines such as INF-gamma or IL-4 in cytoplasm of CD4+ lymphocytes. The frequency of Th1 (INF-gamma containing) cells in p-SS patients was significantly reduced as compared to normal control (20.57+/-7.48% vs 28.78+/-11.56%, p < 0.05), while that of Th2 (IL-4 containing) cells was not different from normal control (3.33+/-0.98% vs 2.85+/-1.88%). The ratio of Th1 to Th2 cells in p-SS patients was significantly decreased as compared to normal control (6.60+/-3.15 vs 11.55+/-6.72, p < 0.05). There was no difference in frequency of Th1 or of Th2 cells between 8 patients given small amounts of prednisolone (PSL) and 7 patients not given PSL (21.44+/-9.39% vs 19.57+/-5.05%, 3.12+/-0.80% vs 3.56+/-1.17%). The percentage of Th1 cells was not different between 7 patients with glandular symptoms (G) and 8 patients with extraglandular symptoms (EG) (18.61+/-9.63% vs 22.27+/-5.02%). Although the frequency of Th2 cells was higher in EG-patients than that in G-patients (3.84+/-0.78% vs 2.74+/-0.86%) with tendency of elevated IgG level in sera, the ratio of Th1 to Th2 cells was not different among them (6.26+/-2.84 vs 6.99+/-3.64). These results suggest that the reduced ratio of Th1 to Th2 cells is essential and is related to the dysfunction of cellular immunity in p-SS.
10635070 [Influence of age on the clinical and biological characteristics of systemic scleroderma]. 1999 Dec PURPOSE: The present study was aimed at assessing the influence of age on clinical and biological features of systemic sclerosis. METHODS: This retrospective study included 151 consecutive patients with systemic sclerosis. The median age at diagnosis was 50.0 years (range: 10-84 years). Patients were divided into two groups according to their age (lower than 50.0 years of age: 73 patients, equal to or above 50 years of age: 78 patients). The following features were compared between the two groups: gender, disease duration, extent of skin sclerosis, Crest syndrome, lung fibrosis, secondary Sjögren's syndrome, antinuclear, anticentromere, and anti-Scl70 antibodies. RESULTS: The disease duration was significantly higher in patients over 50 years of age (7.1 +/- 6.8 years vs 5.5 +/- 5.0 years, P < 0.05). Crest syndrome, secondary Sjögren's syndrome and anticentromere antibodies were significantly more common in patients over 50 years of age (17/73 vs 30/78, P < 10(-2); 9/73 vs 20/78, P < 10(-2), and 19/73 vs 31/78, P < 0.05; respectively). Anti-Scl70 antibodies were significantly more common in patients under 50 years of age (17/73 vs 10/78, P < 10(-2)). No significant difference was found in regard to the other features. CONCLUSION: The clinical and biological patterns of systemic sclerosis are different according to the age at disease onset. Crest syndrome including anticentromere antibodies and Sjögren's syndrome is more common in elderly patients, while anti- Scl-70 antibodies are more common in younger patients. This suggests the involvement of various mechanisms in the pathogenesis of systemic sclerosis, and that these mechanisms may depend on the age.
10627428 Lower frequency of focal lip sialadenitis (focus score) in smoking patients. Can tobacco d 2000 Jan OBJECTIVES: Prospectively collected computer database information was previously assessed on a cohort of 300 patients who fulfilled the Copenhagen classification criteria for primary Sjögren's syndrome. Analysis of the clinical data showed that patients who smoked had a decreased lower lip salivary gland focus score (p<0.05). The aim of this original report is to describe the tobacco habits in patients with primary Sjögren's syndrome or stomatitis sicca only and to determine if there is a correlation between smoking habits and focus score in lower lip biopsies as well as ciculating autoantibodies and IgG. METHODS: All living patients with primary Sjögren's syndrome or stomatitis sicca only, who were still in contact with the Sjögren's Syndrome Research Centre were asked to fill in a detailed questionnaire concerning present and past smoking habits, which was compared with smoking habits in a sex and age matched control group (n=3700) from the general population. In addition, the patients previous lower lip biopsies were blindly re-evaluated and divided by the presence of focus score (focus score = number of lymphocyte foci per 4 mm(2) glandular tissue) into those being normal (focus score 1). Furthermore the cohort was divided into three groups; 10-45, 46-60 and >/= 61 years of age. Finally the focus score was related to the smoking habits. Seroimmunological (ANA; anti-SSA/Ro antibodies; anti-SSB/La antibodies; IgM-RF and IgG) samples were analysed routinely. RESULTS: The questionnaire was answered by 98% (n=355) of the cohort and the percentage of current smokers, former smokers and historical non-smokers at the time of lower lip biopsy was not statistically different from that of the control group. Cigarette smoking at the time of lower lip biopsy is associated with lower risk of abnormal focus score (p<0.001; odds ratio 0.29, 95%CI 0.16 to 0.50). The odds ratio for having focal sialadenitis (focus score > 1) compared with having a non-focal sialadenitis or normal biopsy (focus score /= 61: odds ratio 0.36, 95%CI 0.10 to 1.43) although there was only statistical significance in the two younger age groups. Moreover, among current smokers at the time of the lower lip biopsy there was a decreasing odds ratio for an abnormal lip focus score with increasing number of cigarettes smoked per week (p trend 0.00). In the group of former smokers, which included patients that had stopped smoking up to 30 years ago, the results were in between those of the smokers and the historical non-smokers (odds ratio 0.57, 95%CI 0.34 to 0.97, compared with never smokers). Present or past smoking did not correlate with the function of the salivary glands as judged by unstimulated whole sialometry, stimulated whole sialometry or salivary gland scintigraphy. Among former smokers, the median time lapse between the first symptom of primary Sjögren's syndrome and the performance of the lower lip biopsy was approximately half as long as the median time lapse between smoking cessation and biopsy (8 versus 15 years). Hence, symptoms of Sjögren's syndrome are unlikely to have had a significant influence on smoking habits at the time of the biopsy. Among the seroimmunological results only anti-SSA/Ro and anti-SSB/La antibodies reached statistical significance in a manner similar to the way smoking influenced the focus score in lower lip biopsies. On the other hand the level of significance was consistently more pronounced for the influence of smoking on the focus score than for the influence on anti-SSA/Ro and anti-SSB/La autoantibodies. CONCLUSION: This is believed to be the first report showing that cigarette smoking is negatively associated with focal sialadenitis-focus score >1-in lower lip biopsy in patients with primary Sjögren's syndrome. Furthermore, tobacco seems to decrea
10545525 Defining a novel 75-kDa phosphoprotein associated with SS-A/Ro and identification of disti 1999 Nov Mothers of children with neonatal lupus erythematosus (NLE) and heart block, as well as patients with Sjögren's syndrome (SS) and systemic lupus erythematosus, have serum autoantibodies that recognize SS-A/Ro autoantigens including the 60-kDa ribonucleoprotein. By yeast 2-hybrid screening, we identified a novel 75-kDa protein (pp75) that interacts with the carboxyl 70% of 60-kDa SS-A/Ro. The specificity of interaction was confirmed using mammalian 2-hybrid and chemical crosslinking studies. Immunoprecipitation with radiolabeled HeLa cell extracts showed that pp75 was phosphorylated and associated with 2 other phosphoproteins of 64 kDa. In Northern blot analysis, pp75 was expressed in all tissues analyzed; the highest expression was in the human heart. Based on immunofluorescence of transfected HeLa cells, pp75 is localized predominantly in the cytoplasm, an observation confirmed by immunohistochemistry in untransfected cells. Based on Western blot and ELISA assays, sera from 14 of 84 mothers of children with NLE recognized pp75, including 1 mother in whom anti-SS-A/Ro antibodies were not detected. In addition, sera from 5 of 80 patients with SS were positive for anti-pp75 antibody. Identification of molecular partners is a first step toward elucidating the functions and possible involvement in pathogenesis of long-recognized autoantigens such as 60-kDa SS-A/Ro, which are at present poorly understood.
10222656 Epstein-Barr virus study in malignant lymphoma in Sjögren's syndrome. 1999 Apr The association of Epstein-Barr virus (EBV) with Sjögren's syndrome (SS) is controversial. Reports suggest there is an increased risk of developing lymphoid malignancy in SS. Among our 425 cases of SS, 17 cases of malignant lymphoma (4%), 16 cases of non-Hodgkin's lymphoma (NHL), and 1 case of Hodgkin's disease were found. We looked for an association between EBV and 14 cases of NHL, 13 cases of B-cell lymphoma, and 1 case of T-cell lymphoma in which tissue specimens were available. Epstein-Barr virus-encoded RNA in situ hybridization study and polymerase chain reaction (PCR) study using primers to detect the Bam HI W fragment of EBV with DNA extracts were positive in 2 NHLs: 1 diffuse, large B-cell-type lymphoma, 1 out of 13 cases (8%) of B-cell lymphoma, and 1 angioimmunoblastic T-cell lymphoma with dysproteinemia. In the Bam HI W PCR study of DNA obtained from the labial small salivary glands of 55 cases with SS, 3 cases (5%) were positive. These 3 cases were not associated with malignant lymphoma. Our study revealed that EBV association in SS did not lead to an increased occurrence.
9292794 High prevalence of subclinical Sjögren's syndrome features in patients with autoimmune th 1997 Sep OBJECTIVE: To determine the prevalence of keratoconjunctivitis sicca and xerostomia related to Sjögren's syndrome (SS) in asymptomatic patients with diagnosed autoimmune thyroid diseases (AITD); and to investigate whether the immunopathologies of sialadenitis observed in AITD associated SS and primary SS are similar. METHODS: One hundred seventy-six patients diagnosed with AITD (88 with Graves' disease, 40 Hashimoto's thyroiditis, 48 primary myxedema) were tested for keratoconjunctivitis sicca (Schirmer's test and rose bengal staining) and for xerostomia (salivary scintigraphy and labial salivary gland biopsy). Immunohistopathological studies were performed on cryostat sections of bucal mucosa biopsies using antibodies to CD3, CD4, CD8, CD20, CD14, CD25, LFA-1, ICAM-3 HLA class II, tumor necrosis factor-alpha, interleukin 1, and interferon-gamma. RESULTS: Nineteen of 52 (37%) patients with AITD fulfilled the criteria for xerostomia and 39/170 (23%) for keratoconjunctivitis sicca. Features of SS were diagnosed in 43 of 176 (24%) patients with AITD, with similar prevalence in Graves' (20%). Hashimoto's thyroiditis (27%), and primary myxedema (29%). In AITD associated SS, infiltrating lymphocytes were mainly CD3+ T lymphocytes, with a CD4/CD8 ratio of 2:1. In most patients infiltrating lymphocytes expressed activation markers, HLA class II molecules, and interleukin 2 receptor (CD25). In some patients HLA class II was inappropriately expressed in the epithelial gland cells. CONCLUSION: The finding that a third of patients with AITD have SS features confirms that AITD and SS are mutually associated. Together with the similarity of immunopathology of sialadenitis in AITD associated SS in primary SS, this supports the theory that SS and AITD are 2 autoimmune diseases closely related pathogenetically.
11355874 Human ABCA1 contains a large amino-terminal extracellular domain homologous to an epitope 2001 May 25 ABCA1 has been suggested to play a key role in cellular lipid release from peripheral cells. In order to study structure-function relationship of this protein, the protein product of a full-length human ABCA1 cDNA was examined for its functions and topological orientation. The electrophoretic mobilities of human ABCA1 expressed in transfected cells increased when treated with N-glycosidase F, suggesting that ABCA1 is highly glycosylated. The ABCA1 was photoaffinity-labeled with ATP and mediated the apoA-I-dependent-release of cholesterol and phospholipid. The influenza hemagglutinin (HA) epitope was introduced into the amino-terminus (N-HA) or between the residues 207 and 208 (207-HA) of the protein. While an antibody against the C-terminus peptide of ABCA1 detected both fusion proteins, an anti-HA antibody did not react with the N-HA fusion protein. Confocal microscopy demonstrated strong cell surface signal with the anti-HA antibody of nonpermeabilized HEK293 cells expressing the 207-HA fusion protein. The results suggested that the signal peptide in the amino-terminal region is cleaved off in its mature form and that the following large hydrophilic region is exposed to outside of cells unlike previously proposed models. We found that this amino-terminal extracellular domain contains a segment homologous to the autoantigen SS-N, an epitope of Sjögren's syndrome, and further identified that ABCA7 codes for the autoantigen SS-N.