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ID PMID Title PublicationDate abstract
7575726 Signal transduction through chondrocyte integrin receptors induces matrix metalloproteinas 1995 Sep OBJECTIVE: To study the role of signal transduction via integrin receptors in the production of metalloproteinase by rabbit articular chondrocytes. METHODS: Confluent, primary rabbit articular chondrocytes (RAC) were incubated for 72 hours in the presence of interleukin-1 (IL-1), Arg-Gly-Asp (RGD) peptide, or a combination of IL-1 and RGD peptide. Media were analyzed for stromelysin enzymatic activity using a 3H-labeled transferrin substrate, and for stromelysin and collagenase protein by Western analysis. Gelatinase activity was analyzed by gelatin zymography. IL-1 receptor antagonist (IL-1Ra) protein was used to determine the involvement of IL-1 in mediating the effects of RGD peptide, and fluorescence-activated cell sorter analysis (FACS) was used to examine the effect of IL-1 on chondrocyte integrin subunit expression. RESULTS: RGD peptides induced chondrocyte synthesis of stromelysin, collagenase, and 92-kd gelatinase B, and increased synthesis of the constitutively expressed 72-kd gelatinase A. Further studies focusing on stromelysin demonstrated that this up-regulation was concentration dependent and that RGD peptides synergized with IL-1 in inducing stromelysin synthesis. RGD-induced stromelysin production was inhibited by the IL-1Ra in a concentration-dependent manner, indicating that induction by RGD requires binding of IL-1 to its receptor. FACS analysis of RAC showed that IL-1 stimulation increased the expression of beta 1 and alpha v integrin subunits on the chondrocyte surface. CONCLUSION: Our data demonstrate that signal transduction through chondrocyte integrin receptors up-regulates metalloproteinase expression and that this is likely mediated through induction of IL-1. They also suggest that the binding of adhesion molecules to their chondrocyte integrin receptors reduces the amount of IL-1 required to induce stromelysin synthesis. Up-regulation of chondrocyte integrin expression by IL-1 may play a role in the synergistic effects seen with a combination of IL-1 and RGD peptides. Since elevated levels of both IL-1 and adhesion molecules are present in rheumatoid arthritis and osteoarthritis synovial fluid, our data suggest that this interaction may be important in mediating the cartilage destruction accompanying these diseases.
1472128 Induction of synthesis and release of interleukin-8 from human articular chondrocytes and 1992 Dec OBJECTIVE: The activation of neutrophils in the joint space may contribute to the destruction of cartilage matrix observed in rheumatoid arthritis. The capacity of articular chondrocytes to synthesize and secrete interleukin-8 (IL-8) and GRO alpha, two potent neutrophil chemoattractant peptides, was investigated to determine whether cartilage itself could serve as a source of these small cytokines. METHODS: Induction of IL-8 and GRO protein was studied both at the messenger RNA (mRNA) and the protein level by reverse transcriptase/polymerase chain reaction and metabolic labeling, respectively. RESULTS: Strong induction of IL-8 was observed in primary cultures of articular chondrocytes as well as in cartilage explants stimulated with IL-1 beta. The increased secretion of the IL-8 protein was accompanied by corresponding increases in mRNA levels. In contrast to other connective tissue cells, a peptide corresponding in molecular size to the GRO proteins was only weakly induced in cartilage explants or primary chondrocyte cultures. However, mRNA for all 3 members of the GRO family was easily detectable in cultured chondrocytes following stimulation with IL-1 beta. In explanted cartilage, mRNA for only GRO gamma was found to be induced. Newly synthesized IL-8 was slowly released from cartilage explants over a prolonged time in culture. CONCLUSION: The results suggest that synthesis and secretion of the diverse members of the IL-8/GRO family is regulated in a tissue-specific or cell-specific manner. The slow release of IL-8 from articular cartilage following induction by IL-1 beta could establish a chemotactic gradient toward the articular surface and mediate the migration and attachment of neutrophils and lymphocytes to this tissue.
8318042 Autoantibodies to HMG-17 nucleosomal protein in autoimmune rheumatic diseases. Correlation 1993 Jul OBJECTIVE: Previous studies have shown that serum from patients with systemic lupus erythematosus (SLE) contains antibodies directed against HMG-17, a nucleosomal nonhistone high mobility group (HMG) protein found in chromatin. The aim of the present study was to investigate any associations between the presence of antibodies to HMG-17 and clinical and serologic features of SLE. METHODS: Using porcine thymus as a source, HMG-17 was purified by Sephacryl S-200 chromatography followed by high performance liquid chromatography. An enzyme-linked immunosorbent assay utilizing the purified HMG-17 as antigen was developed and was used to evaluate sera from patients with autoimmune rheumatic diseases, for the presence of autoantibodies. RESULTS: Anti-HMG-17 antibodies were found in the serum of 34.8% of the patients with SLE, compared with 11.5% of patients with primary Sjögren's syndrome, 4.4% of patients with rheumatoid arthritis, and 4.1% of normal blood donors. Analysis of the clinical features of SLE using 2 different lupus activity indices revealed that anti-HMG-17 antibodies were more frequently found in patients with active disease. A positive correlation was also observed between anti-HMG-17 and anti-dsDNA levels, and levels of both of these autoantibodies demonstrated a negative correlation with C4. Analysis of sequentially obtained serum samples from 4 SLE patients revealed that, in 2 patients, anti-HMG-17 levels fluctuated in parallel with both disease activity and anti-dsDNA levels, and in the remaining 2, anti-HMG-17 levels fluctuated in parallel with disease activity. CONCLUSION: Antibodies to HMG-17 are found in patients with many different autoimmune rheumatic diseases, although they are more frequently observed in those with SLE. Their presence appears to be associated with lupus disease activity as well as with anti-dsDNA and C4 levels.
1418007 Serum autoantibody to the nucleolar antigen PM-Scl. Clinical and immunogenetic association 1992 Oct OBJECTIVE: The inflammatory myopathies are characterized by distinctive autoantibodies that are associated with certain clinical features and immunogenetic patterns. Anti-PM-Scl is one such antibody and is found in pure myositis, myositis in overlap, and systemic sclerosis (SSc). Our purpose was to describe the clinical and immunogenetic associations of the anti-PM-Scl antibody. METHODS: Serum samples from 617 patients with various connective tissue diseases were screened for anti-PM-Scl antibody by indirect immunofluorescence and Ouchterlony double immunodiffusion. Patients with anti-PM-Scl were serologically typed for HLA-DR and DQ, and the genes encoding DQ alpha and DQ beta were characterized by hybridization of sequence-specific oligonucleotide to amplified genomic DNA. RESULTS: Twenty-three patients (4%) had serum anti-PM-Scl. Sixteen had either pure myositis or myositis in overlap, 6 had SSc alone, and 1 had SSc and rheumatoid arthritis. Twenty of the antibody-positive patients had serologic HLA typing performed; 15 (75%) were HLA-DR3 positive, and 17 (85%) expressed the DQw2 allele. None of the 5 DR3 negative patients shared a unique DR or DQ antigen with the DR3 positive patients, and further DNA analysis of 10 patients (4 of whom were DR3 negative) did not reveal any unique DQ alleles. CONCLUSION: Anti-PM-Scl identifies a subset of patients with myositis, SSc, or an overlap of the two disorders, and this antibody has a strong but not exclusive immunogenetic association with the HLA-DR3 antigen.
9161229 Comparing TMD diagnoses and clinical findings at Swedish and US TMD centers using research 1996 Summer The Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) guidelines, originally developed in the United States, were translated and used to classify TMD patients on physical diagnosis (Axis I) and pain-related disability and psychologic status (Axis II) in a TMD specialty clinic in Sweden. The objectives of the study were to determine if such a translation process resulted in a clinically useful diagnostic research measure and to report initial findings when the RDC/TMD was used in cross-cultural comparisons. Findings gathered using the Swedish version of the RDC/TMD were compared with findings from a major US TMD specialty clinic that provided much of the clinical data used to formulate the original RDC/TMD. One hundred consecutive patients were enrolled in the study. Five patients with rheumatoid arthritis and 13 children or adolescents were excluded. The remaining 82 patients participating in the study comprised 64 women and 18 men. Group I (muscle) disorder was found in 76% of the patients; Group II (disc displacement) disorder was found in 32% and 39% of the patients in the right and left joints, respectively; Group III (arthralgia, arthritis, arthrosis) disorder was found in 25% and 32% of the patients in the right and left joints, respectively. Axis II assessment of psychologic status showed that 18% of patients yielded severe depression scores and 28% yielded high nonspecific physical symptom scores. Psychosocial dysfunction was observed in 13% of patients based on graded chronic pain scores. These initial results suggest that the RDC guidelines are valuable in helping to classify TMD patients and allowing multicenter and cross-cultural comparison of clinical findings.
1288513 [Plasma- and tissue concentrations following intramuscular administration of etofenamat. P 1992 Dec Studies on Plasma and Tissue Concentrations of Etofenamate following Intramuscular Application/Pharmacokinetics of etofenamate and flutenamic acid in plasma, synovia and tissues of patients with chronic polyarthritis after application of oily etofenamat solution Pharmacokinetics of etofenamate (ETO, CAS 30544-47-9; Rheumon i.m.) and flufenamic acid (FLU, CAS 530-78-9) were investigated in plasma, synovial fluid, and tissues after single intramuscular application of etofenamate to patients with rheumatoid arthritis. 62 patients with indicated operative procedure in the knee-joint received a single dose of etofenamate dissolved in oil before operation. At definite times between 1.5 and 48 h post injectionem samples from 6 patients of each time group were collected. Samples of plasma, synovial fluid, synovial membrane, muscle, bone, hyaline cartilage, and fat tissue and in some cases meniscus cartilage were taken. Concentrations of ETO and its active metabolite, FLU, were determined by HPTLC. In all tissues investigated, concentration/time courses of ETO and FLU were observed. ETO and FLU were measured first in all matrices 1.5 h at the latest 3 h post injectionem. Pharmacokinetics in tissues follows that in plasma. Rate-limiting step is the liberation of drug from the oil depot. For a long period pharmacokinetics of ETO and FLU is mainly determined by the constant liberation from the oil depot (zero order kinetics of liberation). Zero order kinetics is deduced from the linear ascent of the cumulated AUC (in percent) vs. time plot. It is directly related to the liberation of drug from the galenical formulation.(ABSTRACT TRUNCATED AT 250 WORDS)
8014446 Autoimmune liver disease in patients with primary Sjögren's syndrome. 1994 Mar Forty-five patients with primary Sjögren's syndrome were studied for evidence of autoimmune liver disease. Twenty-nine patients had normal liver function tests, normal IgM and a normal test for antimitochondrial antibodies and smooth muscle antibodies. Among the remaining 16 patients, abnormal liver function tests were found in 12 (27% of all patients); eight of these patients had biochemical cholestasis. Elevated plasma IgM (> 2 g/l) was observed in nine patients, three with normal liver function tests, while antimitochondrial antibodies were positive in six patients, one with normal liver function tests, and smooth muscle antibodies were found in three. Based on these findings and percutaneous liver biopsy, a diagnosis of primary biliary cirrhosis was established in four patients and autoimmune chronic active hepatitis in two. The present study showed that abnormal liver function tests in patients with primary Sjögren's syndrome are frequent and may indicate associated autoimmune liver disease. These data further emphasize the systemic nature of autoimmune disorders.
8397319 [Ophthalmologic findings in graft versus host disease (GvHD)]. 1993 Jun BACKGROUND: Since the era of bone marrow transplantation, the picture of acute and/or chronic transplant reaction of the host cells against grafted bone marrow has become more frequent. The so-called adaptive immune therapy bases on the fact that patients who present with a low grade of GvHD less often suffer from a relapse of the malignant leukaemic disease. Therefore, new therapeutic regimen are now performed which keep the patient on a low level of GvHD to prevent a recurrence of leukaemia. Here a close cooperation of oncologists and ophthalmologists becomes more and more important to estimate the stage of GvHD. PATIENTS: Demonstrating two case reports, we report on the ophthalmological symptoms of acute and chronic GvHD. Both patients presented with acute ocular GvHD as well as with signs of chronic ocular GvHD. Concerning the ophthalmological symptoms, in acute or chronic GvHD the conjunctival involvement is most important. There is a lymphocytic infiltration of the conjunctiva and of the lacrimal glands which leads to an extreme sicca-syndrome. The acute GvHD of the conjunctiva can be classified into 4 stages: injection/exudation and chemosis/formation of pseudomembranes/defects of the corneal epithelium. These stages correlate directly to the prognosis of the survival time of the patient. A pathognomonic sign for the chronic GvHD of the conjunctiva are the fibrous-scarry Arlt-lines of the tarsal conjunctiva. CONCLUSIONS: All patients who underwent a bone marrow transplantation for leukaemia need to be followed up closely to estimate the level of GvHD they are in. This applies especially to those patients who are treated according to the regimen of adaptive immune therapy. A close cooperation of oncologists and ophthalmologists during adaptive immune therapy is mandatory, as the ophthalmologist can provide important information to help to grade the level of GvHD, judging by the morphological picture at the slit lamp.
8891116 Biochemical characterization of the reverse transcriptase of a human intracisternal A-type 1996 Sep 20 The discovery of novel human intracisternal A-type particle (HIAP) that may be associated with the autoimmune disease Sjŏgren's syndrome has been previously reported. Although the HIAP retrovirus has been shown to be antigenically related to HIV-1, the viruses were distinguishable by different hydrodynamic mobilities through a sucrose gradient by morphology and intracellular location, and by differing divalent cation requirements for their in vitro reverse transcriptase (RT) reactions. In this report, additional biochemical characteristics are provide that further differentiate the HIAP RT from HIV-1 RT. Data are also presented that distinguish the HIAP RT from the known cellular DNA polymerases.
8543935 Anti-dorsal root ganglion neuron antibody in a case of dorsal root ganglionitis associated 1995 Oct We report the case of a 59-year-old woman with primary Sjögren's syndrome who developed hypesthesia, hypalgesia, and neurogenic arthropathy in her lower limbs. Neurological examination and electrophysiological studies indicated involvement of the dorsal root ganglia. The immunohistochemistry of sections of rat dorsal root ganglion (DRG) showed that the IgG in the serum and cerebrospinal fluid (CSF) from the patient bound to the neuronal perikarya of small DRG neurons but not to the cerebellum or peripheral nerves. These results, consistent with particular impairment of pain and touch senses, suggest that dorsal root ganglionitis in primary Sjögren's syndrome is mediated by humoral autoimmunity.
7761458 Presence of antibodies to different subunits of replication protein A in autoimmune sera. 1995 May 23 A human cDNA expression library was used to investigate the nature of molecules recognized by serum from a patient with Sjögren syndrome that exhibits a mixed immunofluorescence pattern and reacts with multiple components on an immunoblot. The data demonstrated that this serum contains IgG antibodies specific for the 70- and 32-kDa subunits of replication protein A (RPA; RPA-70 and RPA-32, respectively), a highly conserved multisubunit DNA binding protein. Affinity purification of serum autoantibodies demonstrated a complete lack of cross-reactivity between RPA-70 and RPA-32, suggesting a direct participation of the native protein complex in the autoimmune response in this patient. Purified anti-RPA-70 and anti-RPA-32 antibodies labeled nuclear and cytoplasmic components in an immunofluorescence assay, suggesting that RPA is present in both cellular compartments. Additional sera from 55 patients with different autoimmune conditions were screened against purified RPA-70 and RPA-32 recombinant proteins. One of these 55 sera was positive and reacted with only RPA-32. Twenty sera from healthy control individuals did not react with RPA. These results show that RPA is a target for autoantibodies in human autoimmune diseases, although its precise frequency, occurrence in other autoimmune diseases, and pathological significance remain to be fully elucidated.
8751122 Increased levels of Epstein-Barr virus DNA in lacrimal glands of Sjögren's syndrome patie 1995 Oct Many Sjögren's syndrome patients complain primarily of dry eye. Epstein-Barr virus DNA has recently been found in the lacrimal glands of Sjögren's syndrome sufferers and normal individuals, and lacrimal glands are thought to be a target organ for latent Epstein-Barr virus infection. In this study, we performed lacrimal and salivary gland biopsies on 9 Sjögren's syndrome patients. Extracted Epstein-Barr virus DNA was assayed by polymerase chain reaction and compared to that of healthy individuals. An increased level of Epstein-Barr virus DNA was observed in all of the lacrimal glands and 8 of the 9 salivary glands from the Sjögren's syndrome patients. However, the amount of genome in the lacrimal gland was more than 10 times that in the salivary glands, not only in the Sjögren's syndrome patients but also in the controls. This may explain the pathogenesis of dry eye in patients with Sjögren's syndrome, and why the lacrimal gland tends to be so prominently affected. It may also suggest a therapeutic approach for this and possibly other types of dry eye.
7653939 Identification of the T cell antigen receptor V beta gene products in labial salivary glan 1995 T lymphocytes are predominantly involved in the development of Sjögren's syndrome. Their repertoire has recently been claimed to be restricted. Analysis of T cell receptor V beta gene products within the labial salivary glands led us to identify V beta 2 and V beta 8. This study, using a new panel of anti-V beta product monoclonal antibodies and a tissue triple-staining technique, examined the distribution of V beta gene family products in activated as well as non-activated CD4+ or CD8+ T cells subsets in the salivary gland tissue of SS patients. Our results suggest that the V beta genes used by the T CD4+ or T CD8+ cells in situ are similar, irrespective of the activation status of these cells. T lymphocytes homing into exocrine tissues might thus be selected on the basis of their V beta repertoire rather than their activation state.
8106859 Characterization of Epstein-Barr viral strains in parotid gland saliva and peripheral bloo 1993 Dec Increased Epstein-Barr virus (EBV) replication has been reported in the salivary and lacrimal glands in Sjögren's syndrome (SS). We studied whether or not certain EBV strains would occur preferentially in the peripheral blood and parotid gland saliva of 18 EBV-seropositive patients with primary Sjögren's syndrome (pSS) and 12 EBV-seropositive control persons. Transforming EBV was detected in the blood of 11 of 18 (61%) pSS patients and 9 of 12 controls (75%). Unexpectedly, neither transforming nor Raji-superinfecting EBV strains were detected in SS parotid saliva, whereas these EBV types were detected in control saliva in 7 and 8 cases, respectively (P < 0.001). Transforming EBV strains were further characterized by 'Ebno-typing,' i.e., analysis of the size spectrum of the viral antigens EBNA 1, 2, 3, and 6 in immunoblots of lymphoblastoid cell lines (LCL). Previous work has shown that a single EBV strain (Ebnotype) dominates the blood and oropharynx of healthy carriers and that unrelated individuals carry different EBV strains, reflecting the vast polymorphism of Ebnotypes in the general population. Two unexpected observations were made. First, an identical Ebnotype was detected in 4 unrelated individuals, i.e., in the blood of 1 pSS patient and in the saliva of 3 control persons. Second, carriage of 2 to 4 different Ebnotypes by a single individual was observed in 4 cases, i.e., in the blood of 1 pSS patient, and in the blood and saliva of 3 control persons.(ABSTRACT TRUNCATED AT 250 WORDS)
8495261 The molecular basis of the SSA/Ro antigens and the clinical significance of their autoanti 1993 May The SSA/Ro antigens are nuclear and cytoplasmic polypeptides which serve as autoantigens in systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). They contain two major isoforms of 60 and 52 kD. The former is the native antigen while the latter is a major autoantigen in its denatured form. A third protein of 46 kD termed 'calreticulin-Ro' is an autoantigen found in the sera of some patients with SLE. However, it is probably unrelated to the SSA/Ro system. The clinical relevance of anti SSA/Ro antibodies in rheumatic diseases has also been considered. Initially these antibodies were thought to be an epiphenomenon of autoimmune diseases. Recent studies have shown that they are associated with specific clinical manifestations and disease subsets. Furthermore, animal models have demonstrated that they may enhance tissue damage. It seems that anti-SSA/Ro antibodies may play a role in the pathogenicity of SLE and SS.
8938170 Differential recognition of the 52-kd Ro(SS-A) antigen by sera from patients with primary 1996 Dec Antibodies against the 52-kd Ro(SS-A) protein are significantly associated with the primary Sjogren's syndrome (pSS). A small proportion of patients suffering from primary biliary cirrhosis (PBC) with secondary Sjogren's syndrome (PBC/SS) who are serologically characterized by antimitochondrial type 2 antibodies also express anti-52-kd Ro(SS-A) antibodies. The primary B-cell-derived antigenic responses by autoimmune sera were analyzed in both entities using truncated recombinant proteins to examine whether different epitopes are associated with these diseases. Sera were collected from 25 patients with pSS and 9 anti-52-kd Ro(SS-A)-positive patients suffering from PBC/SS. B-cell epitope mapping was performed using different 52-kd Ro(SS-A) fusion proteins in enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Sera from patients with pSS showed the broadest reactivity against antigenic epitopes at AA 153-245 compared to the significantly limited reactivity against AA 228-245 of sera from patients with PBC. B-cell epitopes within AA 190-245 represent immunodominant epitopes recognized by pSS sera in a significantly higher degree than by PBC sera, which react predominantly with AA 228-245 (P < .0001). Anti-La(SS-B) antibodies were significantly associated with anti-52-kd Ro(SS-A) in sera from patients with pSS compared with PBC patients (P < .025). Thus, the antibody response to 52-kd Ro(SS-A) in PBC appears to be induced differently than in pSS. Although a limited immune response to 52-kd Ro(SS-A) occurs in PBC/SS patients, a more extended epitope spreading is evident in patients with pSS.
8607902 Some autoantibodies to Ro/SS-A and La/SS-B are antiidiotypes to anti-double-stranded DNA. 1996 Mar OBJECTIVE: To determine the relationship of anti-Ro/SS-A and anti-La/SS-B antibodies to anti-double- stranded DNA (anti-dsDNA) in sera from patients with systemic lupus erythematosus. METHODS: Sera with anti-Ro/SS-A alone (n = 5) or those with anti-Ro/SS-A and anti-La/SS-B (n = 7) were absorbed with purified Ro/SS-A and La/SS-B, respectively. The absorbed sera were then tested for reactivity with MOLT-4 extract by Western blot and dsDNA by enzyme-linked immunosorbent assay (ELISA). With selected sera, anti-dsDNA was isolated on DNA cellulose columns and anti-Ro/SS-A and anti-La/SS-B were isolated on antigen-affinity columns. Reactivity between anti-dsDNA and autologous anti-Ro/SS-A or anti-La/SS-B, as well as inhibition by cognate antigens, was studied. RESULTS: After absorption, all sera showed reactivity with small nuclear RNP A and D bands in Western blots, and some showed reactivity with dsDNA by ELISA. Anti-dsDNA populations (n = 4) were purified on dsDNA cellulose columns. Anti-Ro/SS-A (n = 1) and anti-La/SS-B (n = 3) were affinity purified from the same sera as the anti-dsDNA. In all cases, anti-dsDNA bound autologous anti-Ro/SS-A and anti-La/SS-B much more strongly than it bound normal pooled IgG. Moreover, dsDNA, but not RNA, blocked these interactions. In addition, Ro/SS-A blocked anti-Ro/SS-A and La/SS-B blocked anti-La/SS-B in these same interactions. CONCLUSION: In sera with anti-Ro/SS-A and anti- La/SS-B, there are subpopulations of these antibodies that bind and mask anti-dsDNA. We hypothesize that these anti-Ro/SS-A and anti-La/SS-B antibodies are antiidiotypes to idiotypes on anti-dsDNA and that they both mask and down-regulate these anti-dsDNA antibodies.
8056525 Sjögren's syndrome: cytokine and Epstein-Barr viral gene expression within the conjunctiv 1994 Aug PURPOSE: In primary Sjögren's syndrome (SS), ocular surface changes within the conjunctival epithelium include lymphocytic infiltration, squamous cell metaplasia, and a reduction in goblet cell number. These changes may be the simple result of increased mechanical abrasion secondary to dryness. Alternatively, they may represent a local response to ocular and/or systemic inflammatory processes, perhaps in response to Epstein-Barr viral (EBV) infection, an agent recently implicated in the etiology of SS. To determine whether inflammatory processes or local infection by EBV contribute to the ocular surface pathology of SS, we examined the expression of inflammatory cell surface markers, cytokines, and EBV gene products within the ocular conjunctiva of patients with SS. METHODS: Ocular conjunctival tissue was isolated from patients with primary SS and nondry eye control patients by impression cytology or direct biopsy. These specimens were examined by immunofluorescence microscopy and reverse-transcriptase polymerase chain reaction (RT-PCR) for the expression of various markers. RESULTS: The authors found the frequency of expression of HLA-DR (P < 0.0001), ICAM-1 (P < 0.035), and IL-6 (P < 0.0001) to be significantly elevated in patients with primary SS versus nondry eye control patients. The IL-2 receptor and cytokines IL-1 beta and IL-8 were each found to be expressed with relatively high frequency in both patient populations, whereas mRNAs encoding cytokines IL-2, IFN-gamma, GM-CSF, and TGF-beta were not reproducibly detectable in either population. Messenger RNA encoding a marker for passive-latent EBV infection (EBNA-1) was detected with high frequency in both SS and normal populations. The EBV IL-10 analog BCRF-1 was expressed with low frequency in the SS population; however, these levels were not significantly different from the control population. The expression of two other markers of EBV infection, latent membrane protein (LMP, a lytic and latent marker), and BZLF-1 (putative latent-lytic switch gene) was undetectable in either study population. CONCLUSION: Based on the increased expression of the cell surface molecules HLA-DR and ICAM-1, and the inflammatory cytokine IL-6, the authors propose that local inflammatory processes contribute to the ocular surface changes and ocular surface dryness associated with primary SS.
7999958 A model to study viral and cytokine involvement in Sjögren's syndrome. 1994 To investigate mechanisms that may be important in the pathogenesis of Sjögren's syndrome (SS) we developed a protocol for the growth of salivary gland epithelial cells in culture. We examined the effect that viral infection has on the cellular location of the autoantigen La. Autoantibodies to La are common in SS and it has been proposed that viral infection may result in cell membrane expression of La. Co-expression of MHC class II molecules in infected cells could lead to the presentation of La peptides to the immune system. Advenovirus infection of salivary gland epithelial cells resulted in an altered nuclear staining of La. Treatment with interferon-gamma resulted in the expression of La in the cell cytoplasm and HLA-DR molecules at the cell surface. These findings suggest that a cytokine-driven mechanism may generate an autoimmune response to La in SS. Using the polymerase chain reaction (PCR) we tested salivary gland epithelial cell cultures for the presence of human herpesvirus-6 (HHV-6) and Epstein-Barr virus (EBV). Only HHV-6 was detected in 2 of 10 salivary gland epithelial cell cultures although the presence of HHV-6 was not associated with SS. Primary salivary gland cultures may prove useful as an in vitro model to study mechanisms of autoimmunity in SS.
8314212 Plasma cell populations in labial salivary glands from patients with and without Sjögren' 1993 Nov Plasma cells expressing IgG, IgA and IgM were quantified in labial salivary glands from patients with Sjögren's syndrome (n = 25) and compared with glands from patients with a variety of systemic diseases (n = 32) and normal individuals (n = 15). Based on qualitative and quantitative analysis, glands from the systemic disease group were divided into normal histology (n = 24) and non-specific inflammation (n = 8) groups. There were no significant differences in cell densities or Ig class proportions between histologically normal glands from patients and those from normal volunteers. Total immunocyte densities were significantly increased in sialadenitis (P < 0.025) and Sjögren's syndrome (P < 0.001) compared with normal histology glands. In both the sialadenitis and Sjögren's syndrome groups there were significant increases in IgG and IgM cell densities (IgG, P < 0.006; IgM, P < 0.001) and proportions (IgG, P < 0.05; IgM, P < 0.001). There were no significant differences in immunocyte densities or proportions between the sialadenitis and Sjögren's syndrome groups except for a lower percentage proportion of IgA cells in the latter (P < 0.038). In all groups the total and individual Ig-class cell densities showed significant positive correlations with extent of leucocyte infiltration (P < 0.01) and negative correlations between IgA and IgG and/or IgM cell proportions. Analysis of the plasma cell data alone and in combination with quantifiable histological parameters failed to yield specific or sensitive diagnostic information. The results suggest that changes in glandular plasma cell populations in Sjögren's syndrome are non-specific.