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ID PMID Title PublicationDate abstract
7558166 The majority of Fc gamma RIII-positive gamma delta T cells do not express HLA-DR in patien 1995 Mar The percentages of circulating gamma delta T cells and the proportions of these expressing Fc gamma RIII (CD16) or HLA-DR in patients with primary Sjögren's syndrome (pSS) and controls were determined using monoclonal antibodies and flow cytometry. There was no significant difference in the percentages of gamma delta T cells in the pSS patients compared with controls. There was, however, a significant increase in the proportions of both CD16+ and HLA-DR+ gamma delta T cells in pSS patients. A 3-colour immunofluorescence technique demonstrated that these two markers were mutually exclusive and therefore may identify either subpopulations of gamma delta T cells or different stages of the activation process.
8031673 Rheumatic manifestations of malignancy. 1994 Jan The rheumatic associations of cancer therapy are highlighted in this review. Interleukin-2, interferon alfa, and Calmette-Guérin bacillus immunotherapies are related to an inflammatory arthritis, and septic arthritis can complicate breast-cancer therapy. In a large retrospective study, an increased incidence of cancer in systemic sclerosis was confirmed, especially lung and breast cancers. Lymphoproliferative associations of Sjögren's syndrome were explored in a study of non-Hodgkin's lymphoma patients in which clinical and histologic criteria were used to diagnose Sjögren's syndrome. B- and T-cell lymphomas continue to be reported with rheumatologic manifestations such as seronegative polyarthritis and sacroiliitis. Malignant angioendotheliomatosis, which mimics central nervous system vasculitis diseases, has been reported. Paraneoplastic associations of lung, ovarian, and renal-cell carcinomas are discussed.
1445456 Antineutrophil cytoplasmic autoantibody-associated vasculitis presenting as Sjögren's syn 1992 Nov A 63-year-old woman, in whom a diagnosis of Sjögren's syndrome was initially made, proved to have systemic vasculitis with salivary gland involvement and necrotizing and crescentic glomerulonephritis. Antineutrophil cytoplasmic autoantibodies (ANCA) against myeloperoxidase were positive. ANCA-associated vasculitis should be considered in the differential diagnosis of Sjögren's syndrome. A positive finding on immunoassay for ANCA against myeloperoxidase or proteinase 3 may help establish the diagnosis.
1408318 Treatment of inflammatory, neuropathic and sympathetically maintained pain in a patient wi 1992 Aug We present a case of Sjögren's syndrome with a painful peripheral neuropathy where pain control required both anti-inflammatory and sympatholytic treatments. This case suggests that the pain in some inflammatory disorders with nerve injury may have a component mediated by an alpha adrenergic receptor.
1626073 Anti-Ro in Sjögren's syndrome and systemic lupus erythematosus. 1992 May Anti-Ro autoantibodies are frequently found in the sera of patients with Sjögren's syndrome, systemic lupus erythematosus, and subacute cutaneous lupus erythematosus as well as in the sera of mothers of infants with the neonatal lupus syndrome. Close associations have been found between anti-Ro and a number of clinical manifestations, particularly including hematologic cytopenias, heart block, and photosensitive skin rashes. Serologic and genetic associations have been found between anti-Ro and anti-La, rheumatoid factor, hypergammaglobulinemia, the histocompatibility alleles DQ1 and DQ2, and alleles of the T-cell receptor beta chain gene. The origin of anti-Ro and other autoantigens is thought to relate to the etiology of Sjögren's syndrome and systemic lupus erythematosus and remains the most fundamental unanswered question preventing a comprehensive understanding of these diseases.
1574305 Orofacial manifestations of mixed connective tissue disease with an uncommon serologic evo 1992 Apr Mixed connective tissue disease is a multisystemic disorder with overlapping features of systemic lupus erythematosus, scleroderma, and polymyositis, and is differentiated from them by a high titer of antibody to ribonucleoprotein. Orofacial manifestations of mixed connective tissue disease include trigeminal neuralgia-like pain, neuropathy, features suggestive of Sjögren's syndrome, and lymphadenopathy. Our recent experience with one patient with trigeminal neuropathy, facial paralysis, Sjögren's syndrome, and aseptic meningitis as early manifestations of the disease, together with an uncommon serologic evolution, is described.
1740830 Ultrasonography of cystic parotid lesions in HIV infection. Similarity of sonographic appe 1992 Jan Bilateral cystic parotid glands occur in some cases of human immunodeficiency virus (HIV) infection. This abnormality, which is associated with cervical adenopathy, can be defined by sonography in the superficial gland, as noted in three men. In retrospect, this parotid disease has similarity to the sonographic finding of Sjögren's syndrome, except for the finding of cervical adenopathy, an observation not previously appreciated.
1379949 Sensitization against pancreatic antigen in Sjögren's syndrome and chronic pancreatitis. 1992 A fractionated pancreatic antigen was prepared using a monoclonal antibody, SP3-1, which reacts with the duct cells of various exocrine organs. The cell-mediated immune response to this antigen was studied by the leukocyte migration inhibition test (LMT) in patients with chronic pancreatitis (CP), Sjögren's syndrome (SjS), and chronic sialoadenitis (CSA). The migration index (MI) for the LMT was 0.97 +/- 0.07 in normal controls (mean +/- SD, n = 11, range: 0.88-1.08). A positive LMT result (MI less than 0.82 = mean -2 SD in controls) was obtained in 7/8 (88%) SjS patients, 4/22 (18%) CP patients, 2/3 CP patients with SjS, and 0/3 CSA patients. These results indicated sensitization against the pancreatic antigen in most SjS patients and some CP patients, and may suggest that an immune response to a common antigenic determinant of the duct cells of exocrine glands plays a role in the pathophysiology of both diseases.
8843857 Identification of autoantibodies to the I protein of the heterogeneous nuclear ribonucleop 1996 Oct OBJECTIVE: To assess the presence of autoantibodies to the 1 protein (polypyrimidine-tract binding protein) of the heterogeneous nuclear RNPs (hnRNP) in different connective tissue diseases. Antibodies to other hnRNP proteins (A1, A2, and B) have been previously found in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCTD). METHODS: Sera from 101 patients with various connective tissue diseases and 25 normal controls were investigated by enzyme-linked immunosorbent assay and immunoblotting, for their reactivity to highly purified recombinant hnRNP I. Moreover, reactivity to cellular hnRNP I protein was investigated by immunoblotting using a partially purified preparation of hnRNP proteins (including A1, A2, B, and I), and by indirect immunofluorescence. For the analysis of the fluorescence pattern, affinity-purified antibodies to hnRNP I; obtained from a selected patient, were tested on HEp-2 cells. RESULTS: By immunoblotting, antibodies reacting to recombinant hnRNP I were found in 22 of 40 patients with systemic sclerosis (SSc), 3 of 32 with RA, 0 of 23 with SLE, and 0 of 6 with MCTD. Antibodies to recombinant hnRNP I were more frequently found in patients with pre-SSc or limited SSc (15 of 24) than in those with intermediate or diffuse SSc (7 of 16). In indirect immunofluorescence studies, affinity-purified anti-hnRNP I autoantibodies gave a diffuse nucleoplasmic staining. Using an hnRNP preparation from nuclear extracts, anti-hnRNP I reactivity was detectable in SSc sera, while it was not detectable in RA, SLE, and MCTD sera reacting with hnRNP A/B proteins. CONCLUSIONS: Human autoimmune sera show distinct patterns of anti-hnRNP reactivity, i.e., anti-A/B in SLE and RA sera, and anti-I in SSc sera. This suggests that A/B proteins and the I protein may be involved in different dynamic hnRNP complexes that elicit different autoimmune responses. From a clinical perspective, anti-hnRNP I antibodies are frequently associated with pre-SSc features, suggesting an early appearance of these antibodies during the course of the disease.
8925840 Functional expression of a fragment of human dihydroorotate dehydrogenase by means of the 1996 Aug 15 Human mitochondrial dihydroorotate dehydrogenase (the fourth enzyme of pyrimidine de novo synthesis) has been overproduced by means of a recombinant baculovirus that contained the human cDNA fragment for this protein. After virus infection and protein expression in Trichoplusia ni cells (BTI-Tn-5B1-4), the subcellular distribution of the recombinant dihydroorotate dehydrogenase was determined by two distinct enzyme-activity assays and by Western blot analysis with anti-(dihydroorotate dehydrogenase) Ig. The targeting of the recombinant protein to the mitochondria of the insect cells was verified. The activity of the recombinant enzyme in the mitochondria of infected cells was about 740-fold above the level of dihydroorotate dehydrogenase in human liver mitochondria. In a three-step procedure, dihydroorotate dehydrogenase was purified to a specific activity of greater than 50 U/mg. Size-exclusion chromatography showed a molecular mass of 42 kDa and confirmed the existence of the fully active enzyme as a monomeric species. Fluorimetric cofactor analysis revealed the presence of FMN in recombinant dihydroorotate dehydrogenase. By kinetics analysis, Km values for dihydroorotate and ubiquinone-50 were found to be 4 microM and 9.9 microM, respectively, while Km values for dihydroorotate and decylubiquinone were 9.4 microM and 13.7 microM, respectively. The applied expression system will allow preparation of large quantities of the enzyme for structure and function studies. Purified recombinant human dihytdroorotate dehydrogenase was tested for its sensitivity to a reported inhibitor A77 1726 (2-hydroxyethyliden-cyanoacetic acid 4-trifluoromethyl anilide), which is the active metabolite of the isoxazole derivative leflunomide [5-methyl-N-(4-trifluoromethyl-phenyl)-4-isoxazole carboximide]. An IC50 value of 1 microM was determined for A77 1726. Detailed kinetics experiments revealed uncompetitive inhibition with respect to dihydroorotate (Kiu = 0.94 microM) and non-competitive inhibition with respect to decylubiquinone (Kic = 1.09 microM, Kiu = 1.05 microM). These results suggest that the immunomodulating agent A77 1726 (currently in clinical phase III studies for the treatment of rheumatoid arthritis) is a very good inhibitor of human dihydroorotate dehydrogenase.
8660387 Oxidative stress: the paradox of aerobic life. 1995 The paradox of aerobic life, or the 'Oxygen Paradox', is that higher eukaryotic aerobic organisms cannot exist without oxygen, yet oxygen is inherently dangerous to their existence. This 'dark side' of oxygen relates directly to the fact that each oxygen atom has one unpaired electron in its outer valence shell, and molecular oxygen has two unpaired electrons. Thus atomic oxygen is a free radical and molecular oxygen is a (free) bi-radical. Concerted tetravalent reduction of oxygen by the mitochondrial electron-transport chain, to produce water, is considered to be a relatively safe process; however, the univalent reduction of oxygen generates reactive intermediates. The reductive environment of the cellular milieu provides ample opportunities for oxygen to undergo unscheduled univalent reduction. Thus the superoxide anion radical, hydrogen peroxide and the extremely reactive hydroxyl radical are common products of life in an aerobic environment, and these agents appear to be responsible for oxygen toxicity. To survive in such an unfriendly oxygen environment, living organisms generate--or garner from their surroundings--a variety of water- and lipid-soluble antioxidant compounds. Additionally, a series of antioxidant enzymes, whose role is to intercept and inactivate reactive oxygen intermediates, is synthesized by all known aerobic organisms. Although extremely important, the antioxidant enzymes and compounds are not completely effective in preventing oxidative damage. To deal with the damage that does still occur, a series of damage removal/repair enzymes, for proteins, lipids and DNA, is synthesized. Finally, since oxidative stress levels may vary from time to time, organisms are able to adapt to such fluctuating stresses by inducing the synthesis of antioxidant enzymes and damage removal/repair enzymes. In a perfect world the story would end here; unfortunately, biology is seldom so precise. The reality appears to be that, despite the valiant antioxidant and repair mechanisms described above, oxidative damage remains an inescapable outcome of aerobic existence. In recent years oxidative stress has been implicated in a wide variety of degenerative processes, diseases and syndromes, including the following: mutagenesis, cell transformation and cancer; atherosclerosis, arteriosclerosis, heart attacks, strokes and ischaemia/reperfusion injury; chronic inflammatory diseases, such as rheumatoid arthritis, lupus erythematosus and psoriatic arthritis; acute inflammatory problems, such as wound healing; photo-oxidative stresses to the eye, such as cataract; central-nervous-system disorders, such as certain forms of familial amyotrophic lateral sclerosis, certain glutathione peroxidase-linked adolescent seizures, Parkinson's disease and Alzheimer's dementia; and a wide variety of age-related disorders, perhaps even including factors underlying the aging process itself. Some of these oxidation-linked diseases or disorders can be exacerbated, perhaps even initiated, by numerous environmental pro-oxidants and/or pro-oxidant drugs and foods. Alternatively, compounds found in certain foods may be able to significantly bolster biological resistance against oxidants. Currently, great interest centres on the possible protective value of a wide variety of plant-derived antioxidant compounds, particularly those from fruits and vegetables.
1522211 Antibodies to T- and L-isoforms of the cytoskeletal protein, fimbrin, in patients with sys 1992 Sep The cytoskeleton is a complex network of proteins that maintain cell shape, mobility, and organelle function. Its components can be divided into three distinct classes: microfilaments, microtubules, and intermediate filaments. Fimbrins are microfilament proteins, a family of cytoplasmic phosphoproteins. Expression of the L-fimbrin isoform is restricted to replicating blood cells and expression of the T-fimbrin isoform to replicating cells of solid tissues. Sera from normals and from patients with systemic lupus erythematosus (SLE), juvenile arthritis, rheumatoid arthritis, Sjögren's syndrome, osteoarthritis, vasculitis, scleroderma, and mixed connective tissue disease were tested for the presence of antibodies to T- and L-fimbrin by ELISA, using purified recombinant fimbrin. The mean OD of sera from SLE patients was significantly higher than in normals (T-fimbrin, P less than 0.0001; L-fimbrin, P less than 0.001). 48 of 98 SLE sera had antibodies to T-fimbrin; 32 had antibodies to L-fimbrin; 20 had antibodies to both; 28 had only anti-T, and 12 had only anti-L-fimbrin. The mean OD for sera of the other rheumatic diseases was not significantly different from normals. The presence of either L- or T-fimbrin antibody was associated with pleuropericarditis (P = 0.015), photosensitivity (P = 0.011), and anti-Sm antibody (P = 0.010). Central nervous system SLE was associated with the presence of the L-fimbrin antibody alone (P = 0.016). There was a strong association between DR7 (but not other MHC alleles) and anti-L-fimbrin antibodies in SLE patients (chi square = 18; P less than 0.00002). No MHC association was observed with anti-T-fimbrin antibodies.
8649581 Pitfalls in the diagnosis of autoantibodies associated with paraneoplastic neurologic dise 1996 Jun We studied the sera of 15 patients with Sjögren's syndrome using the Western blot technique for the presence of anti-Ro and anti-Hu (type 1 antineuronal nuclear autoantibody [ANNA-1]). All sera reacted with Ro-52 protein. Two of the Sjögren sera reacted with 38-kd bands on Western blots of rat cerebellar homogenate, resembling anti-Hu immunoreactivity. However, when reacted with purified human Purkinje cells or purified recombinant HuD protein, none of the sera immunoreacted with the Hu antigens. We recommend the use of either a recombinant Hu protein or the combination of immunohistochemistry and Western blot of purified human neuronal preparations to identify paraneoplastic antibodies. This approach will prevent the unnecessary workup for suspected lung cancer.
7621031 T-cell receptor V alpha and V beta gene use by infiltrating T cells in labial glands of pa 1995 Jun Sjögren's syndrome is an autoimmune disease affecting the exocrine glands; it is thought to result from T-cell-mediated damage. In the labial glands of 20 patients with Sjögren's syndrome, infiltrating T cells were immunohistochemically characterized, and T-cell receptor (TCR) gene expression was examined with a method based on polymerase chain reaction. Most of these lymphocytes expressed CD3, CD4, CD45RO, and TCR alpha beta, whereas less than 5% of them expressed CD25 and CD69. The TCR V alpha and V beta genes expressed in peripheral blood mononuclear cells were diverse, whereas the TCR V alpha and V beta repertoires in the labial glands were more restricted but were still heterogeneous. The predominantly used V alpha and V beta families in the labial glands, when compared with those in peripheral blood mononuclear cells, were found to vary in individual patients and also to differ from patient to patient. Thus the T-cell population in the labial glands was polyclonal but showed a more restricted pattern than that seen in peripheral blood mononuclear cells.
7481483 In vivo and in vitro expression of adhesion molecules by peripheral blood lymphocytes from 1995 The interaction of adhesion receptors on lymphocytes with their ligands over endothelial cells provides the mechanism by which lymphocytes infiltrate target tissues in autoimmune diseases. Primary Sjogren's syndrome (SS) is associated with lymphocytic infiltration in exocrine glands. The aim of this study was to examine levels of expression of adhesion molecules by peripheral blood lymphocytes from patients with SS (before and after stimulation). Peripheral blood lymphocytes from 16 patients with primary SS and from 15 controls were stained directly or cultured for 72 h with and without phytohaemagglutinin (PHA). Indirect immunofluorescence with monoclonal antibodies and flow cytometry were used. The following molecules were detected in patients before culture: CD18 (mean percentage 94%), CD11a (94%), CD11b (39%), CD54 (23%), CD58 (62%), CD44 (Hermes-1; 82%), CD49-d (VLA-4; 80%), CD25 (11%) and LECAM-1 (62%). After stimulation with PHA, there was an increase in the levels of CD18 (2.5-fold), CD11a (2.3-fold), CD54 (10.2-fold), CD58 (2.5-fold), CD44 (2.4-fold), CD49d (3.4-fold) and CD25 (62-fold) on lymphocytes from both patients and controls. The number of positive cells and level of expression did not differ from the controls, except in the case of unstimulated, cultured lymphocytes in which the levels of CD44 and LECAM-1 were increased more in patients than in normal controls. The increase in the level of in vitro expression of CD44 (P < 0.05) and LECAM-1 (P < 0.002) on lymphocytes from patients with primary SS reached statistical significance when compared to similarly cultured lymphocytes from controls.(ABSTRACT TRUNCATED AT 250 WORDS)
8231110 Exocrinopathy resembling Sjögren's syndrome induced by a murine retrovirus. 1993 Oct BACKGROUND: Sjögren's syndrome (SS) is characterized by lymphocytic infiltration into, and destruction of exocrine glands, resulting in dryness of the mouth and eyes. The disease is considered to have an autoimmune etiology, however, its etiopathogenesis remains largely unknown. Recently, retrovirus is suggested to participate in the pathogenesis of SS, because SS-like lesions are reported in HIV infection or in human T cell leukemia virus type I infection. Moreover, human intracisternal A-type retroviral particles are reported to be detected in SS patients. During the course of our study on the histopathology of mice infected with a murine retrovirus, we happened to find SS-like exocrinopathy in those mice. EXPERIMENTAL DESIGN: Four-week-old C57BL/6 (B6) mice were injected intraperitoneally with LP-BM5 murine leukemia virus. This virus is known to induce splenomegaly, lymphadenopathy followed by lymphoid malignancy, and profound immunodeficiency in sensitive strains of mice. From 4 to 16 weeks after the virus inoculation, the infected mice were sacrificed and their submandibular and lacrimal glands were analyzed light and electron microscopically and immunohistochemically. The existence of the virus in the lesion in situ was also analyzed by the same method, and additionally by a polymerase chain reaction method. RESULTS: Periductal lymphocytic infiltration into the submandibular and lacrimal glands was observed in all the virus-infected mice at 4 weeks after the infection and progressed with time. Extraglandular lymphocytic infiltration was also observed in liver, kidney, lung, and pancreas. Immunohistochemical examination revealed that most infiltrating cells into the glands were composed of CD3+ T cells (CD4-dominant), Mac-1+ cells, and B220+ cells. The virus genome was detected in submandibular glands by immunohistochemistry or by polymerase chain reaction. In addition, retroviral particles were secreted into the lumen of exocrine ducts of submandibular glands. CONCLUSIONS: This might be an SS animal model that is induced by a certain defined retrovirus. This experimental system might provide us with valuable information for analyzing the mechanisms of how a retrovirus could induce SS.
7621030 Immunoglobulin gene rearrangements in lymphoplasmacytic infiltrates of labial salivary gla 1995 Jun OBJECTIVES: Sjögren's syndrome is an autoimmune disorder in which patients have a well-recognized risk of developing malignant lymphoma. Although some clinical parameters may herald the onset of lymphoma, few reliable histologic or molecular markers are available that predict progression to a malignant lymphoproliferative disorder. The purpose of this study was to identify the prevalence of immunoglobulin heavy chain monoclonality in labial gland biopsies of patients with Sjögren's syndrome and to compare this to clinical outcome. STUDY DESIGN: The polymerase chain reaction was applied to 76 sequential labial salivary gland biopsies from patients under investigation for Sjögren's syndrome. A seminested polymerase chain reaction technique was used on DNA extracted from formalin-fixed, paraffin-embedded tissue to amplify the V-D-J region of the immunoglobulin heavy chain gene. Thirty-four randomly selected labial salivary glands that showed nonspecific sialadenitis from patients without Sjögren's syndrome were used as controls. RESULTS: Monoclonality, as defined by a single band on polyacrylamide gel electrophoresis was detected in 11 cases (14.5%). Of cases that showed monoclonality, four patients were subsequently diagnosed with extrasalivary lymphoma. In each case the rearranged bands in the lip biopsy and the lymphoma were the same size. In one patient who later developed lymphoma, a monoclonal rearranged immunoglobulin band was not identified. In addition, no cases of the translocation t(14;18) were identified by polymerase chain reaction in any of the lip biopsies showing heavy chain monoclonality or in any of the extrasalivary gland lymphomas. CONCLUSIONS: These results suggest that monoclonal immunoglobulin heavy chain gene rearrangements are a relatively common finding in patients with Sjögren's syndrome and may prove to be a useful marker for predicting the progression to, and early detection of malignant lymphoma.
8374701 Analysis of granulocyte-reactive antibodies using an immunoassay based upon monoclonal-ant 1993 Jun To detect human granulocyte-reactive antibodies, a glycoprotein-specific enzyme immunoassay for platelet antibodies was adapted for the use of granulocytes as target cells. Peripheral blood granulocytes were simultaneously incubated with a monoclonal antibody (mAb) and the serum to be investigated. After solubilization, aliquots of the cell lysate were transferred to plastic tubes coated with goat anti-mouse antibodies. Following immobilization of the trimolecular (mAb-glycoprotein-human antibody) complex it was detected by addition of enzyme-labelled goat anti-human antibodies using a luminescence technique. This assay allowed identification of different granulocyte-reactive antibodies present in the same sample without the need for complicated absorption studies. Alloantibodies against HLA and the granulocyte-specific NA antigens as well as isoantibodies against the Fc-gamma-receptor III (FcRIII) were detectable using mAb-specific immobilization of granulocyte antigens (MAIGA). Binding of autoantibodies to the FcRIII and to the CD 11b/CD18 complex could be shown.
9010048 T-cell receptor repertoire of infiltrating T cells in lachrymal glands, salivary glands an 1996 Dec Alymphoplasia (aly) mice are thought to provide a new model for systemic Sjögren's syndrome (SS), since they reveal remarkable infiltration of mononuclear cells into salivary glands, lachrymal glands and kidneys, and show histological findings similar to those in patients with SS. Cell transfer experiments demonstrate that T cells induce the infiltration of mononuclear cells into several tissues in aly mice. To analyse the pathogenesis of cell infiltration in various tissues, we examined T-cell receptor (TCR) V beta usage of T cells in salivary glands, lachrymal glands and kidneys from aly mice, using family-polymerase chain reaction (PCR) and PCR-single-strand conformation polymorphism (SSCP) methods. The results of SSCP demonstrated that the infiltrating T cells in the three organs expanded clonally, suggesting that they proliferate by antigen-driven stimulation. Some TCR V beta genes (V beta 1, 3, 6, 11, 12, 16) were commonly used in salivary glands, lachrymal glands and kidneys, while the V beta 7 gene was specifically expressed in kidneys. SSCP also showed that there were a few shared T-cell clones (V beta 3- and V beta 6-positive cells) among the three tissues. Indeed, sequence analysis of accumulated T cells showed that a conserved amino acid (leucine) at position 98 in the TCR V beta complementary determining region (CDR) 3 was detected in all organs at high frequency (41-57%) and the amino acid sequence motif (LG) was specifically conserved at a frequency of 32% in the three organs. In conclusion, T cells that infiltrate into lachrymal glands, salivary glands and kidneys of aly mutant mice might recognize shared common epitopes in all three organs and a kidney-specific antigen.
8639174 Increased expression of human thioredoxin/adult T cell leukemia-derived factor in Sjögren 1996 May OBJECTIVE: To determine the involvement of human thioredoxin/adult T cell leukemia-derived factor TRX/ADF) in Sjögren's syndrome (SS) and the correlation with Epstein-Barr virus (EBV). METHODS: Indirect immunohistochemical techniques and reverse transcriptase polymerase chain reaction were utilized to analyze TRX/ADF expression and the presence of EBV, using 6 normal tissues and 23 surgical specimens. The kinetics of expression of TRX/ADF induced by EBV was examined in vitro with peripheral blood B cells from EBV-seronegative donors. RESULTS: Marked expression of TRX/ADF was found in the infiltrating B cells and the epithelial cells of salivary gland tissues from patients with SS (11 of 12 cases), but not in those from patients with other salivary gland inflammatory conditions (0 of 11 cases) or those of normal individuals (0 of 6 cases). In immunohistologic analyses, a striking topographic correlation between TRX/ADF and EBV was found. The coexistence of TRX/ADF messenger RNA and EBV DNA was detected by polymerase chain reaction (r = 0.75, P < 0.01). Peripheral blood B cells from EBV-seronegative donors showed de novo synthesis of TRX/ADF following in vitro infection with EBV. EBV-infected B cell lines all expressed TRX/ADF. TRX/ADF was not detected in non-EBV-infected cells. Tumors in SCID mice reconstituted with mononuclear cells of salivary glands from SS patients, which were composed of human B cells carrying EBV DNA, were positive for TRX/ADF. CONCLUSION: These findings suggest that TRX/ADF expression closely reflects the intracellular event of EBV reactivation in SS. This is also the first report to show the ectopic in vivo expression of TRX/ADF in human autoimmune disease.