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ID PMID Title PublicationDate abstract
9046734 Hypergammaglobulinemic purpura associated with Sjögren's syndrome and chronic C type hepa 1997 Jan Although hypergammaglobulinemic purpura usually occurs secondarily on the lower legs in several disorders, purpura has also recently been reported to be associated with chronic C type hepatitis (HCV). To define the differences in the clinical, histological and laboratory findings and the prognosis of hypergammaglobulinemic purpura associated with those two disorders, we examined ten patients with hypergammaglobulinemic purpura, 6 patients with hypergammaglobulinemic purpura associated with Sjögren's syndrome (SjS) and 4 patients with hypergammaglobulinemic purpura with chronic C type hepatitis. Five of 6 patients with SjS were female. Attacks of purpura occurred in the pretibial area in all cases. Triggering factors included long walks and prolonged standing. The mean duration of attacks was 6.4 days. No systemic manifestations were associated. Anti-Ro/SS-A and anti-La/SS-B antibodies were expressed in one case. Spontaneous regression was noted in all cases; however, recurrence was noted in one. On the other hand, all the 4 patients with hypergammaglobulinemic purpura associated with HCV were men. Purpura was indurated in a few cases. Involved sites included the knee, forearm, abdomen and thigh in addition to the lower leg. The mean duration of attacks was 12.6 days. Recurrent purpura was noted in one case. Cryoglobulin was positive in three cases. In one patient with severe recurrent purpura, attacks stopped with prednisolone 10 mg/day. Histologically, leukocytoclastic vasculitis was detected in three cases associated with SjS and two cases with HCV. In conclusion, hypergammaglobulinemic purpura associated with HCV appears to occur unilaterally with a sex predilection for men and the manifestations last longer than those associated with SjS. Severe palpable purpura was also noted in association with HCV; systemic prednisolone resulted in good control.
11139286 G-protein signaling abnormalities mediated by CD95 in salivary epithelial cells. 2000 Nov Salivary epithelial cells from patients with primary Sjögren's syndrome (SS) undergo Fas-mediated apoptosis. Bcl-2 and Bcl-xL are apoptosis suppressing oncogenes. Very little is known about the role of these oncogene molecules in salivary epithelial cells. To investigate the possible prevention of salivary glandular destruction in SS by Bcl-2 and Bcl-xL, stable transfectants expressing these molecules were made from HSY cells, a human salivary epithelial cell line. HSY cells were transfected with an expression vector for human Bcl-2 or Bcl-xL. Stable transfectants were selected and apoptosis was induced by anti-Fas antibody. Apoptosis was quantified by propidium iodide staining followed by flow cytometry. Caspase activity was detected by immunohistochemical analysis and enzyme cleavage of DEVD-AMC, a fluorescent substrate. Response to carbachol, a muscarinic receptor agonist, and EGF was measured by Ca2+ mobilization and influx. Fas-mediated apoptosis was significantly inhibited in Bcl-2 and Bcl-xL transfectants compared to wild-type and control transfectants (empty vector). Surprisingly, caspase activity was not inhibited in Bcl-2 and Bcl-xL transfectants. Activation of the Fas pathway in the Bcl-2 and Bcl-xL transfectants by antibody also inhibited carbachol and EGF responsiveness (i.e., Ca2+ mobilization and/or influx) by 50-60%. This Fas-mediated inhibition of cell activation was partially or completely restored by specific peptide interference of caspase enzyme activity. The prevention of Fas-mediated apoptosis by the overexpression of Bcl-2 and Bcl-xL in salivary gland epithelial cells results in injured cells expressing caspase activity and unable to respond normally to receptor agonists. Such damaged cells may exist in SS patients and could explain the severe dryness out of proportion to the actual number of apoptotic cells seen on salivary gland biopsy.
10825406 Renal involvement in primary Sjögren's syndrome. 2000 May Renal involvement was evaluated in 62 patients with primary Sjögren's syndrome, classified according to criteria proposed by The European Classification Criteria Group. Urine concentration capacity was tested using intranasal 1-desamino-8-D-arginine-vasopressin. For patients with urine pH>5.5 without metabolic acidosis (n=28), an acidification test with ammonium chloride was performed. Urinary citrate, albumin, NAG, ALP and beta2-microglobulin were measured and creatinine clearance was calculated. Maximum urine concentration capacity and creatinine clearance were reduced in 13 (21%). Albumin excretion was >30 microg/min in only one patient (1.6%). Seven patients (11.3%) had complete or incomplete distal renal tubular acidosis (dRTA), four had reduced creatinine clearance and five had reduced maximum urine concentration capacity. The ratio of citrate/creatinine in spot urine was below the 2.5 percentile in all patients with complete or incomplete dRTA. The prevalence of dRTA was lower than in previous studies. There were also few patients with signs of glomerular disease (1.6%). The use of citrate:creatinine ratio in spot urine can be a helpful method in identifying patients with complete or incomplete dRTA.
11238560 Bonzo/CXCR6 expression defines type 1-polarized T-cell subsets with extralymphoid tissue h 2001 Mar Chemokine receptor expression is finely controlled during T-cell development. We show that newly identified chemokine receptor Bonzo/CXCR6 is expressed by subsets of Th1 or T-cytotoxic 1 (Tc1) cells, but not by Th2 or Tc2 cells, establishing Bonzo as a differential marker of polarized type 1 T cells in vitro and in vivo. Priming of naive T cells by dendritic cells induces expression of Bonzo on T cells. IL-12 enhances this dendritic cell-dependent upregulation, while IL-4 inhibits it. In blood, 35-56% of Bonzo+ CD4 T cells are Th1 cells, and 60-65% of Bonzo+ CD8 T cells are Tc1 cells, while few Bonzo+ cells are type 2 T cells. Almost all Bonzo+ Tc1 cells contain preformed granzyme A and display cytotoxic effector phenotype. Most Bonzo+ T cells lack L-selectin and/or CCR7, homing receptors for lymphoid tissues. Instead, Bonzo+ T cells are dramatically enriched among T cells in tissue sites of inflammation, such as rheumatoid joints and inflamed livers. Bonzo may be important in trafficking of effector T cells that mediate type 1 inflammation, making it a potential target for therapeutic modulation of inflammatory diseases.
11842924 What can transgenic and gene-targeted mouse models teach us about salivary gland physiolog 2000 Dec Thousands of genetically modified mice have been developed since the first reports of stable expression of recombinant DNA in this species nearly 20 years ago. This mammalian model system has revolutionized the study of whole-animal, organ, and cell physiology. Transgenic and gene-targeted mice have been widely used to characterize salivary-gland-specific expression and to identify genes associated with tumorigenesis. Moreover, several of these mouse lines have proved to be useful models of salivary gland disease related to impaired immunology, i.e., Sjögren's syndrome, and disease states associated with pathogens. Despite the availability of genetically modified mice, few investigators have taken advantage of this resource to better their understanding of salivary gland function as it relates to the production of saliva. In this article, we describe the methods used to generate transgenic and gene-targeted mice and provide an overview of the advantages of and potential difficulties with these models. Finally, using these mouse models, we discuss the advances made in our understanding of the salivary gland secretion process.
10841323 Hypercoagulability in various autoimmune diseases: no association with factor V Leiden mut 2000 The coagulation factor V Leiden mutation, leading to resistance to activated protein C (APC), is the most common inherited risk factor for venous thrombosis. In various systemic autoimmune diseases the hypercoagulable state was shown to be associated with the presence of antiphospholipid antibodies (aPL). Our aim was to determine the prevalence of both, Leiden mutation and aPL in autoimmune diseases and their impact on the occurrence of venous thrombosis. The dataset consists of results from 137 patients having Sjögren's syndrome (n = 50), progressive systemic sclerosis (n = 43) (PSS), undifferentiated connective tissue disease (n = 24) (UCTD) and mixed connective tissue disease (n = 20) (MCTD) with or without venous thromboembolic complications. The Leiden mutation was detected with polymerase chain reaction (PCR), aPL, such as lupus anticoagulant (LA) with screening and confirmatory procedures and others with enzyme linked immunosorbent assay (ELISA). The prevalence of mutation ranged between 8.3% and 18.0% (13.1%). The thromboembolic risk was found to be increased in the presence of aPL. Eight patients (5.84%) (4 heterozygous) experienced thromboembolic events and 3 out of 4 heterozygous showed aPL positivity, too. There were no difference between the frequencies of Leiden mutation in examined systemic autoimmune diseases and unselected populations.
10414853 Immunocytochemical localisation of neuropeptide-containing nerve fibres in human labial gl 1999 May Different neuropeptide-containing nerve fibers (vasoactive intestinal polypeptide, substance P, neuropeptide Y) and nitric oxide synthase (NOS) positive nerve fibers were investigated to clarify their role in the function of human labial glands using immunohisto- and immunocytochemical techniques. The distribution pattern of all immunoreactive nerve fibers was similar both in the control and in the Sjögren's syndrome specimens. A large number of thin varicose vasoactive intestinal polypeptide and NOS positive nerve fibers were seen around or in close contact with the acini. Some of the immunoreactive nerve fibers were associated with the salivary ducts and blood vessels. Substance P and neuropeptide Y immunoreactive nerve fibers were located mainly around the blood vessels. Immunocytochemistry demonstrated that some of the positive nerve fibers were in direct contact with the acini, blood vessels and with the lymphocytes. The gap between the membranes of immunoreactive nerve terminals and the target cells was 40 to 200 nm. The number of the nerve terminals in Sjögren's syndrome specimens was decreased and some degenerated axons were also found. These results suggest that these neuropeptides and nitric oxide might act as a neurotransmitter in the regulation of secretion and blood flow in the labial glands. These fibers might also alter the neuroimmunological processes, because the investigated neuropeptides are known to be immunoregulators.
9631746 Enhanced neutrophil and eosinophil adhesion in patients with primary Sjögren's syndrome. 1998 May OBJECTIVE: To study granulocyte adhesion to E-selectin, VCAM-1 and ICAM-1 in patients with primary Sjögren's syndrome (pSS). In previous studies diminished neutrophil adhesion has been shown as measured by the nylon fiber method. METHODS: Neutrophil and eosinophil adhesion to the adhesion molecules E-selectin, VCAM-1 and ICAM-1 were measured using transfected fibroblasts. The cell surface expression of the integrin proteins CD11a, CD11b, CD18 and CD29 on neutrophils was assayed by means of flow cytometry. RESULTS: Neutrophils and eosinophils from patients with pSS had elevated basal adhesion in the presence of Mn2+ as compared with controls (basal adhesion was considered to be the adhesion to untransfected fibroblasts). Granulocyte adhesion to E-selectin was also elevated. No differences were seen between patients and controls in cell surface expression of the integrin proteins CD11a, CD11b, CD18 and CD29 on neutrophils, nor was there any difference in these parameters between patients with and without extra glandular symptoms. CONCLUSIONS: These results suggest that blood neutrophils and eosinophils are activated in pSS. Accordingly they do not confirm results from earlier studies of impaired neutrophil adhesion in pSS.
11737657 Lactoferrin, amylase and mucin MUC5B and their relation to the oral microflora in hyposali 2001 Dec There are several reasons for hyposalivation, each affecting the salivary composition in different ways. The aim of this study was to analyze and compare lactoferrin, amylase and mucin MUC5B in stimulated whole saliva collected from subjects with hyposalivation of different origins and to relate the results to the presence of some microbial species associated with oral disorders. Albumin was determined as a marker of serum leakage. The characteristic feature for subjects with radiation-induced hyposalivation was a large increase in lactoferrin, probably due to leakage through inflamed mucosal tissues, while it was a high albumin content for the group with primary Sjögren's syndrome, probably due to disruption of the fragile mucosa. The saliva composition in subjects with hyposalivation of unknown origin or due to medicines was close to that in the healthy controls. All three hyposalivation groups tended to display a decrease in the concentrations of MUC5B and amylase. None of the microbial species analyzed (streptococci, mutans streptococci, Lactobacillus spp., Fusobacterium nucleatum, Prevotella intermedia/Prevotella nigrescens, Candida albicans, Staphylococcus aureus and enterics) correlated with concentration of MUC5B in saliva. The RT group, having the highest concentration of lactoferrin, had the lowest median number of F. nucleatum and was the only group in which median number of P. intermedia/P. nigrescens was zero.
10204807 Sjögren's syndrome: lymphoma predisposition coupled with a reduced frequency of t(14;18) 1999 Mar Sjögren's syndrome (SS) is a systemic autoimmune disorder with a strong tumor predisposition (a 44-fold elevated incidence of non-Hodgkin's lymphoma has been reported). By polymerase chain reaction analysis of t(14;18), a key lymphomagenic event in peripheral blood lymphocytes, we found a lower frequency in a subset of 12 SS patients positive for SS-A/SS-B autoantibodies than in 21 healthy subjects and 20 SS patients lacking these SS marker autoantibodies (P < 0.001). All 14 mutants sequenced displayed signs typical of V(D)J recombinase activity. This perplexing result of a low rate of t(14;18) in a population strongly predisposed to t(14;18)-associated tumor development may be explained by a constitutive deficiency in V(D)J recombinase leading to autoimmunity and increased lymphoproliferation.
10998315 Analysis of cytokine production in the colon of nude mice with experimental colitis induce 2000 Oct LP-BM5 murine leukemia virus (MuLV) is known to induce murine AIDS (MAIDS). We have shown that Sjögren's syndrome (SjS)-like exocrinopathy can be induced in mice with MAIDS and that adoptive transfer of spleen cells from MAIDS mice can induce inflammatory bowel disease-like colitis as well as SjS-like exocrinopathy in nude mice. To assess the role of interferon (IFN)-gamma and interleukin (IL)-10 in the pathogenesis of our experimental model, we tried to identify the cells producing these cytokines and their localization in the colitis lesions in situ. Expression of mRNA for IFN-gamma and IL-10 was assessed by RT-PCR, and protein expression of these cytokines was also analyzed in frozen sections of colon by double-color-staining immunofluorescence (IF). An increase of IFN-gamma and IL-10 mRNA was detected in the colon of mice with colitis, but not in that of control mice. Double-color IF showed that Mac-1(+) cells were positive for IFN-gamma or IL-10 and that most CD4(+) T cells were positive for IL-10, although the population of IFN-gamma-positive CD4(+) T cells was low. In our experimental colitis model, Mac-1(+) macrophages that produce both IFN-gamma and IL-10 might play a crucial role in the pathogenesis of colitis in combination with CD4(+) T cells.
9415639 T cell reactivity to Sjögren's syndrome related antigen La(SSB). 1997 Dec OBJECTIVE: Many patients with primary Sjögren's syndrome (SS) make high titer IgG autoantibodies to the La(SSB) antigen, suggesting antigen specific T cell-B cell interactions. T cell responses to some nuclear antigens, particularly U1RNP, have been detected in patients with systemic lupus erythematosus (SLE) and in healthy subjects. We investigated T cell reactivity to the autoantigen SSB in patients with SS and healthy controls. METHODS: Using the [3H]thymidine proliferation assay, we determined reactivity to purified recombinant SSB (rSSB) in 20 patients with SS and 19 controls. Specificity was determined using tetanus toxoid, endotoxin, and 3 other autoantigens (PBC.M2, Sc170, and GAD). Precursor frequency was calculated by limiting dilution analysis. HLA Class II dependency was investigated using anti-Class II monoclonal antibodies. HLA-DR typing was by polymerase chain reaction and sequence specific oligonucleotide typing. RESULTS: Six of 20 patients with SS and 10/19 controls proliferated to La(rSSB). Precursor frequency of anti-SSB T cells was 1:77,040 and 1:115,000 in 2 healthy subjects and 1:230,250 and 1:103,034 in two patients with SS. Anti-HLA-DR abrogated proliferation to SSB and tetanus toxoid. Thirteen of 15 patients with SS and 4/17 controls were HLA-DR3 positive, with no apparent association of HLA-DR3 with SSB reactivity in controls. CONCLUSION: Anti-La(SSB) specific T cells occur in a significant proportion of controls and in some patients with SS. The function of SSB T cells in controls remains to be defined. They may represent immunoregulatory cells, and further analysis of these cells, and a comparison to those found in patients with SS, may elucidate normal immunoregulation and the derangements that lead to Sjögren's syndrome.
9444417 Complement regulatory proteins in the salivary glands and saliva of Sjögren's syndrome pa 1997 Nov OBJECTIVE: The aim of this study was to examine the presence of the complement regulatory proteins protectin (CD59), decay accelerating factor (CD55), membrane cofactor protein (CD46) and clusterin (SP-40,40) in connection with the autoimmune exocrinopathy in Sjögren's syndrome (SS). METHODS: Labial salivary gland biopsy specimens and saliva samples were obtained from SS patients and healthy subjects. The tissue expression of these proteins was assessed by ABC immunoperoxidase techniques. Saliva was analysed by immunoblotting methods. RESULTS: Tissues from healthy subjects expressed CD59 and CD46 on the apical/luminal surfaces of acinar and ductal epithelial cells. CD59, CD55, and SP-40,40 were expressed in interstitial tissues. In SS tissues, the expression of CD55, CD59, CD46 and SP-40,40 was up-regulated, following the same patterns of tissue localization as the controls. CD46 and SP-40,40 exhibited a much higher staining intensity in SS patients compared to controls. CD55, CD59 and SP-40,40 were present at high concentrations in saliva from SS patients. CONCLUSION: The presence of complement regulators in our SS patients' saliva and the high expression of these proteins in inflamed salivary gland tissue followed the inflammatory reaction. These regulators may be involved in protecting the exocrine glands from complement mediated injury.
11465713 Synergistic effects of glycoprotein 130 binding cytokines in combination with interleukin- 2001 Jul OBJECTIVE: To determine whether other glycoprotein 130 (gp130) binding cytokines can mimic the effects of oncostatin M (OSM) in acting synergistically with interleukin-1alpha (IL-1alpha) to induce cartilage collagen breakdown and collagenase expression, and to determine which receptors mediate these effects. METHODS: The release of collagen and proteoglycan was assessed in bovine and human cartilage explant cultures. Messenger RNA (mRNA) and protein production from immortalized human chondrocytes (T/C28a4) was analyzed by Northern blotting and specific enzyme-linked immunosorbent assays. Collagenase activity was measured by bioassay. Cell surface receptors were detected by flow cytometry. RESULTS: OSM in combination with IL-1alpha caused a rapid synergistic induction of matrix metalloproteinase 1 mRNA, which was sustained over a 72-hour period. Flow cytometric analyses detected both the OSM-specific receptor and the gp130 receptor at the chondrocyte cell surface, but failed to detect the leukemia inhibitory factor receptor (LIFR). Cartilage degradation assays revealed that, of the gp130 binding cytokines, only OSM and IL-6, in the presence of its soluble receptor (sIL-6R), were able to act synergistically with IL-1alpha to promote collagen release. CONCLUSION: This study demonstrates that IL-6 can mimic OSM in synergizing with IL-1alpha to induce chondrocyte-mediated cartilage collagen breakdown and collagenase production. In order to have this effect, IL-6 requires the presence of its soluble receptor. The apparent absence of LIFR explains why other gp130 binding cytokines do not act in synergy with IL-1alpha. Since OSM, IL-6, and sIL-6R levels have all been shown to be elevated in the rheumatoid joint, our findings suggest that these cytokines may be key mediators of cartilage collagen catabolism in the inflammatory arthritides.
11819916 [Pharmacology of non-steroidal anti-inflammatory drugs and ENT pathology]. 2001 Dec 22 1. BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAID) belong to a variety of chemical classes with no common features except the absence of a steroid structure. Their primary effect is pain relief, but also with anti-pyretic and anti-inflammatory effects. Basically prescribed for symptomatic relief, they do not have a curative effect on chronic disease processes. 2. INFLAMMATORY EFFECTS OF PROSTANOIDS (THROMBOXANE A2 AND PROSTAGLANDINS): Inflammation basically results from the pro-algogenic and vascular effects of prostanoids. Their pro-algogenic effects are explained by sensitization of nociceptive nerve endings to the stimulating effect (algogenic) of kinins (bradykinin), serotonin and histamine. In addition, production of prostanoids in the brain has a thermoregulatory effect. 3. MODE OF ACTION: NSAID have a common effect, inhibiting the production of prostanoids via reduced activity of two cyclo-oxygenases (COX-1 and COX-2). COX-2 is an isoform predominantly expressed during the inflammatory process. Excepting two compounds recently marketed (celecoxib, rofecoxib) selective for COX-2, all other NSAID have few or no selective properties. COX-1 is implicated in the regulation of many physiological functions. Inhibition of COX-1 explains most of the classical side effects of non-selective NSAID. 4. COMPARISON: It is classical to emphasize the interindividual variable anti-inflammatory and antalgesic effects of the different NSAID without developing a coherent explanation. In addition, it is very difficult to make objective comparisons between different NSAID because of the different sizes of the study populations, indications and dosages. There is no evidence favoring a given NSAID on the basis of its anti-inflammatory or antalgesic effect in a given indication; no hierarchy in terms of efficacy can be established. For acute pain, it is preferable to use oral NSAID absorbed rapidly to achieve rapid relief. 5. PARACETAMOL: This antalgesic, antipyretic drug has no anti-inflammatory action. Its mechanism of action remains to be fully elucidated. It is not a member of the NSAID class and is a poor inhibitor of COX, particularly COX-2 (30% maximal inhibition). For identical dose (1-3 g/d), the antalgesic activity of paracetamol is comparable to that of aspirin for pain in general. There does not appear to be any difference in the anti-pyretic efficacy between NSAID and paracetamol. 6. OFFICIAL INDICATIONS: In general, NSAID are not indicated for anti-inflammatory action in the ENT conditions discussed here. It this light, the official indications in France published on November 14, 1988 concerning ENT disease in children and adults without risk factors is most noteworthy. It is stipulated that there is no need to institute NSAID treatment at an anti-inflammatory dose in combination with general antibiotic therapy, except when there is an important inflammatory component. This guideline does not concern NSAID at antalgesic and antipyretic doses used for ENT conditions with or without an infectious component. 7. SELECTIVE INHIBITORS OF COX-2: Selective inhibitors are only indicated in two chronic inflammatory diseases: osteoarthritis and rheumatoid arthritis. There is no indication for these inhibitors in ENT disease. The only beneficial effect that has been demonstrated to date for the use of selective inhibitors of COX-2 is better digestive tract tolerance. 8. ROLE OF PROSTANOIDS IN THE CLINICAL EXPRESSION OF ALLERGIC RHINITIS: It is insufficient to warrant use of NSAID in this disease, particularly due to the efficacy of anti-H1 and local corticosteroids. NSAID are not indicated in nasal polyposis and are even contraindicated in case of intolerance to NSAID, observed in about 15-20% of all patients with nasal polyposis. However, local application of lysine acetylsalicylate at progressive doses from 20 micrograms to 4 mg can reduce relapse by half after polypectomy. There is no proof of the efficacy of NSAID in chronic sinusitis and their efficacy has not been studied in laryngitis. Finally, there is no sufficient evidence, either from experimental data or clinical trials, to recommend NSAID for otitis, with the exception for an antalgesic and/or antipyretic effect. 9. CHOOSING AN ANTI-INFLAMMATORY OR ANTALGESIC NSAID: The choice is generally guided by the frequency and severity of undesirable effects. These undesirable effects often appear during the first weeks of treatment. 10. DIFFERENT ADVERSE EFFECTS: Digestive tract effects appear in 20 to 40% of the patients after a few weeks of treatment using anti-inflammatory doses. Symptomatic gastroduodenal ulcers, digestive bleeding, and perforations are the most serious adverse effects of NSAID. Nevertheless, the risk of such complications, compared with the number of prescriptions, is very low. At high dose (anti-inflammatory dose), age over 60 years and history of severe gastrointestinal complications are factors increasing the risk of severe gastrointestinal adverse effects of NSAID. Minor adverse effects, and more importantly severe adverse effects, are significantly reduced with selective COX-2 inhibitors compared with classical NSAID. It is important to note that these beneficial effects in terms of tolerance are not better than with NSAID treatments except for treatments at anti-inflammatory doses for more than one week. Selective COX-2 inhibitors would have the same adverse effect on the kidney as classical NSAID, as pointed out by the precautions for use published by the manufacturers. COX-2 is not expressed by platelets. Specific inhibitors do not inhibit platelet aggregation and do not lengthen bleeding time. Specific inhibitors, like classical NSAID, are not recommended for women desiring pregnancy, especially because the risk of a teratogenic effect has not been excluded. Conversely, for patients with asthma triggered by classical NSAID, selective COX-2 inhibitors do not trigger acute asthma. Finally, selective COX-2 inhibitors are not currently indicated for children and not for ENT disease.
10782167 Coexisting thymic and gastric lymphomas of mucosa-associated lymphoid tissues in a patient 2000 May Lymphomas of mucosa-associated lymphoid tissues (MALTomas) arising from the thymus are extremely rare. In this case report, we describe a 36-year-old woman with an 11-year history of Sjögren syndrome who was found to have a thymic MALToma coexisting with a gastric MALToma. Both tumors shared similar histologic features, showing clusters of centrocytic-like B cells, lymphoepithelial lesions, and prominent plasmacytic differentiation. They also showed the following identical immunohistochemical features: CD20(+), IgA/lambda(+), CD5(-), and CD43(-). Molecular studies using polymerase chain reaction methods revealed monoclonal gene rearrangement of the immunoglobulin heavy chain in the gastric MALToma, but not in the thymic MALToma. The possible pathogenesis of this unusual case is discussed.
9546818 Neonatal lupus erythematosus: studies on HLA class II genes and autoantibody profiles in J 1997 Neonatal lupus erythematosus (NLE) is a rare disorder of neonates characterized by two major clinical manifestations: congenital heart block and cutaneous lupus lesions. The disease is associated with placentally transferred maternal anti-Ro/SSA and/or La/SSB antibodies. To clarify possible class II HLA associations with maternal autoantibody responses, haplotypic and allelic distributions, along with the polymorphism of the MHC class II HLA alleles, were analyzed based on PCR-RFLP results in 25 Japanese mothers of two groups defined by precipitating autoantibody profiles. Among mothers with both anti-Ro/SSA and anti-La/SSB antibodies, but not those with anti-Ro/SSA alone, the class II haplotypes DRB1*1101-DQA1*0501-DQB1*0301 and DRB1*08032-DQA1*0103-DQB1*0601 as well as individual class II alleles DRB1*1101, DRB1*08032 and DQB1*0301 showed significantly increased frequencies compared to those in normal controls. All anti-Ro/SSA and anti-La/SSB positive mothers carried DRB1 alleles that shared the same amino acid residues at positions 14-31 and 71 of the DRB1 chain. These mothers also carried homozygous or heterozygous DQ6 and DQ3 alleles that shared the same amino acid residues at positions 27-36 and 71-77 of hypervariable regions of the DQB1 chain. Furthermore, all mothers with both anti-Ro/SSA and anti-La/SSB were homozygous for DPB1*0501. Nine of 10 anti-Ro/SSA and anti-La/SSB-positive mothers, but only 6 of 15 mothers with anti-Ro/SSA alone, had affected infants. Thus, our findings suggest that there may be immunogenetic differences among mothers according to their autoantibody profiles, and that mothers with both anti-Ro/SSA and anti-La/SSB are more likely to have infants with NLE than mothers with anti-Ro/SSA alone.
9155673 Retrovirus in salivary glands from patients with Sjögren's syndrome. 1997 Mar AIMS: To investigate the possibility of an immune response to retroviral antigens or of detecting retrovirus in Sjögren's syndrome. METHODS: Retroviruses were sought in labial salivary glands and peripheral blood mononuclear cells from patients with Sjögren's syndrome by immunoblotting assay, immunohistochemical assay, polymerase chain reaction (PCR), reverse transcriptase (RT) activity assay, and transmission electron microscopy. RESULTS: Sera from five of 15 patients with Sjögren's syndrome (33%) reacted against p24 group specific antigen (gag) of human immunodeficiency virus (HIV). Labial salivary gland biopsy specimens from seven of the 15 patients with Sjögren's syndrome (47%) contained an epithelial cytoplasmic protein reactive with a monoclonal antibody to p24 of HIV. PCR was performed to detect HIV and human T lymphotropic virus type I (HTLV-I) genes from salivary gland tissues and peripheral blood mononuclear cells from patients with Sjögren's syndrome. Mn2+ dependent, Mg2+ independent RT activity was detected in the salivary gland tissues in three of 10 patients. A-type-like retroviral particles were observed in epithelial cells of salivary glands by transmission electron microscopy. Target genes for HIV and HTLV-I were not found in any of the salivary gland tissues or peripheral blood mononuclear cells from Sjögren's syndrome patients. CONCLUSIONS: The data suggest the presence of an unknown retrovirus similar to HIV in the salivary gland which might be involved in the pathogenesis of a subpopulation in Sjögren's syndrome.
9130458 Modulation of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) by interferon-gamma in a human 1997 May Gelatinases have been shown to be regulated by many cytokines and growth factors, and have been implicated in the pathogenesis of certain autoimmune diseases via tissue destruction. High levels of several cytokines, including IFN-gamma and TNF-alpha, have been demonstrated in the salivary gland microenvironment of patients with Sjogren's syndrome (SS). How these cytokines may be contributing to the pathogenesis of this disease is not well understood. We hypothesized that IFN-gamma with or without (+/-) TNF-alpha could be playing a role in the pathogenesis of SS via the regulation of matrix metalloproteinase (MMP) levels. This study examined the role of IFN-gamma and (+) TNF-alpha in the regulation of the matrix metalloproteinases, MMP-2 (72 kD gelatinase A) and MMP-9 (92 kD gelatinase B). A human salivary gland cell line (HSG) has been used as a possible in vitro model to study the role of IFN-gamma + TNF-alpha in the pathogenesis of SS. The HSG cell line, in the presence of IFN +/- TNF-alpha, displays increased MMP-2 and MMP-9 gelatinolytic activity, protein and RNA levels. The increase in MMP activity was partially blocked with an antibody against the IFN-gamma receptor, and this was associated with a complete inhibition of the previously described IFN-gamma +/- TNF-alpha antiproliferative effect. However, incubation of IFN-gamma treated HSG cells with the synthetic MMP inhibitor BB94 did not alleviate this antiproliferative effect. In addition, we demonstrate that there are very high levels of MMP-9 in the saliva of patients with SS when compared to healthy control subjects. These data suggest that cytokines could be regulating MMP production by salivary epithelial cells and thus indicate a potential role for these cells in the pathogenesis of SS.
11666014 Primary extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue 2001 Sep Extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type has been reported in various internal organs. Here a case is reported of MALT lymphoma developing in the cerebellopontine (CP) angle in a patient with Sjogren syndrome, and the concept of MALT lymphoma of the CNS is introduced. Pathologically, the tumor showed inflammatory features of reactive lymphocytic infiltration with follicle formation, but there were slightly atypical lymphocytes and plasmacytes with B-cell markers. These cells invaded reactive follicles, showing follicular colonization, and showed aberrant expression indicating their neoplastic nature. A review of the literature revealed eight cases of MALT lymphoma originating from the dura mater and one from the CP angle. The average age of patients was 50 years (range 28-66 years), and all patients were female. The tumors were slow to develop and the patients were cured after surgical removal and/or additional therapies. It is proposed that MALT lymphoma should be considered as a differential diagnosis of inflammatory pseudotumor of the CNS.