Anti-tumor necrosis factor therapy in patients with difficult-to-treat lupus nephritis: a prospective series of nine patients.

OBJECTIVE: To clarify the efficacy and safety of anti-TNF-alpha therapy for intractable lupus nephritis. METHODS: In nine patients with systemic erythematosus who presented with lupus nephritis resistant to steroids and immunosuppressants, 200 mg/body of infliximab was drip-infused three times. No changes were made to other treatments for three months after the start of anti-TNF-alpha therapy, and urinary findings, renal function, serum complement, anti-DNA antibody, SLE activity, and adverse events were examined for six months after the start of anti-TNF-alpha therapy. RESULTS: One of the nine patients developed pyelonephritis after the first infliximab injection and received no further injections. The remaining eight patients received 3 infliximab injections. Of the eight patients, urinary protein decreased after anti-TNF-alpha therapy in six patients, and the SLEDAI improved in five patients. Urinary findings and/or SLE activity improved in six patients. Of the patients whose urinary protein levels decreased after anti-TNF-alpha therapy, proteinuria recurred six months after anti-TNF-alpha therapy in one patient. After anti-TNF-alpha therapy, proteinuria and the SLEDAI improved significantly. With respect to adverse events, therapy was discontinued in one patient who developed pyelonephritis, and one patient developed decreased blood pressure due to infusion reactions. In one patient in whom the steroid dosage was increased due to poor response to anti-TNF-alpha therapy, brainstem infarction occurred four months later. In one patient, anti-DNA antibody levels increased after therapy, but none of the patients had decreased serum complement levels or increased SLE activity. CONCLUSION: In intractable lupus nephritis, anti-TNF-alpha therapy improved urinary protein levels and SLE activity. Although adverse events must be monitored cautiously, it may be possible to use anti-TNF-alpha therapy as a third-line treatment.

Activation of pulmonary T cells in corticosteroid-resistant and -sensitive interstitial pneumonitis in dermatomyositis/polymyositis.

To study the activation states and cytokine profiles of pulmonary T cells in corticosteroid-resistant and corticosteroid-sensitive interstitial pneumonitis (IP) in dermatomyositis (DM)/polymyositis (PM), we examined the activation markers and cytokine profiles of T cells in bronchoalveolar lavage fluids (BALF) from patients with IP in DM/PM before prednisolone therapy and then compared the activation states of T cells according to the therapeutic response of IP to prednisolone therapy. CD25+ CD4+ T cells in BALF were significantly increased in both corticosteroid-resistant and corticosteroid-sensitive IP in DM/PM as compared with those in controls without IP. Furthermore, CD25+ CD4+ T cells in BALF were significantly more increased in corticosteroid-resistant IP than those in cortico teroid- sensitive IP. Moreover, CD25+ CD8+ T cells in BALF were significantly increased only in corticosteroid-resistant IP, but not in corticosteroid-sensitive IP or controls without IP. IFN-gamma mRNA was detected in BALF T cells in corticosteroid-resistant and corticosteroid-sensitive IP but not in controls without IP, whereas IL-4 mRNA was virtually undetected in BALF T cells in both the IP groups. However, there were no significant differences in CD4/CD8 ratio of BALF T cells, HLA-DR+ BALF T cells or CD25+ and HLA-DR+ peripheral blood T cells between the two IP groups. These results indicate that activated Th1-type pulmonary T cells play an important role in the development of corticosteroid- resistant IP in DM/PM and that the increase in CD25+ CD8+ T cells in BALF is a useful indicator for corticosteroid-resistant IP in DM/PM and hence may be an indicator for early use of cyclosporin.

Expression of TNF-related apoptosis inducing ligand (TRAIL) on infiltrating cells and of TRAIL receptors on salivary glands in patients with Sjögren's syndrome.

BACKGROUND: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) induces apoptosis of tumor cells but not normal cells; its role in normal non-transformed tissues is unknown. OBJECTIVE: To evaluate the role of apoptosis mediated by TRAIL and TRAIL-receptor (TRAIL-R) system in lymphocytic sialadenitis in patients with Sjögren's syndrome. METHODS: The expression of TRAIL and TRAIL-R1, 2, 3 and 4 in lymphocytic sialadenitis was examined by immunoperoxidase staining in patients with Sjögren's syndrome and in normal subjects. To elucidate the mechanism of de novo expression of TRAIL-R1 antigen, we quantitatively investigated its induction by cytokines in human salivary duct cell line (HSG) by cell enzyme-linked immunosorbent assay. In human salivary duct cells stimulated by cytokines, we investigated the induction of apoptotic cell death by recombinant TRAIL protein. RESULTS: In patients with massive mononuclear cell infiltration, some infiltrating cells showed TRAIL. In patients with severe lymphocytic sialadenitis, TRAIL-R1, TRAIL-R2, or both were strongly expressed on the ductal epithelial cells. Neither TRAIL-R3 nor R4 were observed on ductal epithelium. In contrast, TRAIL-R1 and R2 were not found in the minor salivary glands of normal subjects or patients with mild lymphocytic sialadenitis. Unstimulated HSG cells did not express TRAIL-R1. Interferon-gamma (IFN-gamma) consistently upregulated levels of TRAIL-R1. In contrast, tumor necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL-1 beta), IL-2, and IL-4 had no effect on TRAIL-R1 levels. HSG cells expressing TRAIL-R1 in response to IFN-gamma were susceptible to apoptosis by recombinant TRAIL protein. CONCLUSION: Our findings suggest that TRAIL and TRAIL-R system may play a role in the pathogenesis of lymphocytic sialadenitis in patients with Sjögren's syndrome.

Increase of dendritic cells of type 2 (DC2) by altered response to IL-4 in atopic patients.

BACKGROUND: Recent studies have shown that there are 2 dendritic cell subpopulations, DC1 and DC2, which induce T(H)1 and T(H)2 cell differentiation in vitro, respectively. OBJECTIVE: The purpose of this study was to determine whether there exists a deviation of DC1 and DC2 subsets and to investigate their functional abnormalities in T(H)2 cell-mediated atopic diseases. METHODS: We analyzed the frequencies of DC1 (CD11c(+)CD123(-)) and DC2 (CD11c(-)CD123(+)) cells in peripheral blood of atopic patients; we also studied the responses of DC2 cells from atopic patients to IL-3 and IL-4 for their survival. RESULTS: DC2 cells but not DC1 cells were significantly increased in peripheral blood of atopic patients in comparison with that of healthy subjects. DC2 cell numbers were positively correlated with serum IgE levels and blood eosinophil counts, the increase of which reflects T(H)2-type immune response in atopic diseases. IL-4 inhibited IL-3-induced survival of DC2 cells from healthy controls, but IL-4 failed to suppress the IL-3-induced survival of DC2 cells from atopic patients. Furthermore, IL-4 alone enhanced the survival of DC2 cells from atopic patients but not from healthy controls. However, no significant differences were found in the expression levels of activation/maturation markers on DC2 cells between atopic patients and healthy controls. CONCLUSION: These results indicate that DC2 cells are preferentially increased in atopic patients in correlation with the state of atopic allergy and that DC2 cells in atopic patients, unlike those in healthy subjects, exhibit altered responses to IL-4 for survival, suggesting that DC2 cells in atopic patients might contribute to the enhanced T(H)2 cell differentiation in atopic diseases.

A novel nucleolar protein, NIFK, interacts with the forkhead associated domain of Ki-67 antigen in mitosis.

In a previous study, we demonstrated that the forkhead associated (FHA) domain of pKi-67 interacts with the novel kinesin-like protein, Hklp2 (Sueishi, M., Takagi, M., and Yoneda, Y. (2000) J. Biol. Chem. 275, 28888-28892). In this study, we report on the identification of a putative RNA-binding protein of 293 residues as another binding partner of the FHA domain of pKi-67 (referred to as NIFK for nucleolar protein interacting with the FHA domain of pKi-67). Human NIFK (hNIFK) interacted with the FHA domain of pKi-67 (Ki-FHA) efficiently in vitro when hNIFK was derived from mitotically arrested cells. In addition, a moiety of hNIFK was co-localized with pKi-67 at the peripheral region of mitotic chromosomes. The hNIFK domain that interacts with Ki-FHA was mapped in the yeast two-hybrid system to a portion encompassed by residues 226-269. In a binding assay utilizing Xenopus egg extracts, it was found that the mitosis-specific environment and two threonine residues within this portion of hNIFK (Thr-234 and Thr-238) were crucial for the efficient interaction of hNIFK and Ki-FHA, suggesting that hNIFK interacts with Ki-FHA in a mitosis-specific and phosphorylation-dependent manner. These findings provide a new clue to our understanding of the cellular function of pKi-67.

[A case of systemic lupus erythematosus with hemophagocytic syndrome and cytophagic histiocytic panniculitis].

A 23-year-old man, admitted because of high fever, polyarthralgia, butterfly rash and chest pain, was diagnosed as systemic lupus erythematosus (SLE) from the findings of positive antinuclear antibody and anti-DNA antibody. He was treated with 60 mg prednisolone daily, but as reducing the dose, white blood cell counts and platelet counts were decreased and fever, polyarthralgia, decrease of complements, increase of ferritin, hepato-splenomegaly and liver dysfunction were observed. Bone marrow specimen revealed phagocytosis of blood cells by histiocytes and he was diagnosed as hemophagocytic syndrome(HPS) due to active SLE. Methylprednisolone pulse therapy was effective temporarily, HPS recurred while reducing steroid, and cyclosporin was added. After a temporary remission, marked extensive swelling in the face appeared suddenly. Facial skin biopsy showed necrosis of fat cells and hemophagocytosis by histiocytes. Accordingly, he was diagnosed as panniculitis due to HPS and was treated successfully with intravenous cyclophosphamide pulse therapy and high dose of gammaglobulin. Several cases of HPS due to SLE have been reported recently, but this is a rare case of cytophagic histiocytic panniculitis (CHP) due to SLE.

Glandular and extraglandular expression of costimulatory molecules in patients with Sjögren's syndrome.

OBJECTIVES: To investigate the expression and regulation of CD80, CD86, and CD28 costimulatory molecules in sialoadenitis and interstitial nephritis in patients with Sjögren's syndrome (SS). METHODS: Expression of CD80, CD86, and CD28 molecules was studied by immunohistochemical staining of lip biopsy specimens obtained from patients who had sialoadenitis associated with SS, and renal biopsy specimens obtained from patients who had interstitial nephritis associated with SS. To elucidate the mechanism of de novo expression of CD80 and CD86 antigens, their induction by cytokines in human salivary duct cell line (HSG) and renal cortical epithelial cells (HRCE) by cell enzyme linked immunosorbent assay (ELISA) was quantitatively investigated. RESULTS: In patients with severe sialoadenitis, CD80 and CD86 were strongly expressed on ductal epithelial cells. In contrast, these antigens were not found in the minor salivary glands of normal subjects or of patients with mild sialoadenitis. Some infiltrating cells expressed CD28. In patients who had interstitial nephritis associated with SS, some tubular epithelial cells expressed CD86 but not the CD80 antigen. Unstimulated HSG cells did not express CD80 or CD86. Interferon gamma (IFNgamma) consistently up regulated levels of CD80 and CD86. In contrast, tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), IL2, and IL4 had no effect on either CD80 or CD86 levels. Unstimulated HRCE did not express CD80 or CD86. IFNgamma consistently up regulated CD86 expression. No CD80 expression was found on tubular cells. TNFalpha, IL1beta, IL2, and IL4 had no discernible effects. CONCLUSIONS: Salivary ductal cells in patients with SS can express CD80 and CD86 costimulatory molecules in response to IFNgamma. Tubular epithelial cells in patients who have interstitial nephritis associated with SS express only CD86 molecules. In patients with SS, salivary ductal cells and tubular epithelial cells may activate infiltrating CD28 positive T lymphocytes by presenting antigens to T cells, potentially leading to tissue destruction.

Interferon gamma and tumor necrosis factor alpha induce Fas expression and anti-Fas mediated apoptosis in a salivary ductal cell line.

BACKGROUND: We previously reported that Fas antigen was strongly expressed on salivary duct epithelial cells and that some salivary infiltrating cells showed the Fas ligand in patients with severe sialoadenitis due to Sjögren's syndrome (SS). Apoptotic changes were observed in ductal epithelial cells and some infiltrating cells by DNA nick end labeling methods. These findings suggest that the Fas-Fas ligand system may play a role in the pathogenesis of sialoadenitis in SS. OBJECTIVE: To elucidate the mechanism of the de novo expression of ductal Fas antigen in sialoadenitis associated with SS, we investigated the induction of Fas antigen and apoptosis by cytokines in a human salivary duct cell line. METHODS: Human salivary duct cell line (HSG) was cultured with interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), interleukin 2 (IL-2), interleukin 4 (IL-4), and granulocyte monocyte colony stimulating factor (GM-CSF). The expression of Fas antigen in HSG was examined by immunoperoxidase cell ELISA. The appearance of DNA strand breaks during apoptosis induced by anti-Fas antibody was detected by DNA nick end labeling methods. RESULTS: Unstimulated HSG cells constitutively expressed low levels of Fas antigen. IFN-gamma and TNF-alpha consistently upregulated constitutive levels of Fas. In contrast, IL-1 beta, IL-2, IL-4, and GM-CSF had no effect on Fas levels. HSG cells expressing Fas antigen in response to IFN-gamma or TNF-alpha were susceptible to apoptosis by anti-Fas antibody. CONCLUSION: Our findings suggest that IFN-gamma or TNF-alpha secreted by infiltrating lymphocytes induces ductal Fas expression and ductal apoptosis in sialoadenitis associated with SS.

The forkhead-associated domain of Ki-67 antigen interacts with the novel kinesin-like protein Hklp2.

The Ki-67 antigen (pKi-67) is widely used as a cell proliferation marker protein. Its actual role in the cell cycle progression, however, is presently unclear. Using a two-hybrid screening in yeast, a novel protein, termed Hklp2 (human kinesin-like protein 2), was identified and shown to interact with the forkhead-associated (FHA) domain of pKi-67. Hklp2 has 1388 amino acids and shows a striking similarity (a 53% identity in amino acids) to Xklp2, a plus-end directed kinesin-like motor found in Xenopus. The interaction domain of Hklp2 was mapped to the portion that comprised residues 1017-1237 and that was phosphorylated in vitro by incubating with mitotic but not interphasic HeLa cell extracts. That the interaction was striking in the mitotic extract was also verified. In addition, immunofluorescence using specific antibodies revealed an association between pKi-67 and Hklp2 at the periphery of mitotic chromosomes, largely in close proximity to the centromeres. These findings suggest that pKi-67 is involved in the progression of mitosis via its interaction with Hklp2.

Regulation of CD69 expression on eosinophil precursors by interferon-gamma.

The purpose of this study was to determine whether interferon-gamma (IFN-gamma) induced CD69 expression by eosinophil precursors. Eosinophil precursors were induced from CD34+ cord blood cells using recombinant human interleukin-3 (IL-3) and interleukin-5 (IL-5). On day 14 of culture, cells constitutively expressed CD69 and the IFN-gamma receptor (IFN-gammaR). Stimulation with IFN-gamma for 24 h did not affect IFN-gammaR expression by the cells. On the other hand, IFN-gamma significantly upregulated CD69 expression by the precursors after 24 h of incubation. A specific JAK2 inhibitor (AG-490) caused a concentration-dependent suppression of IFN-gamma-induced CD69 expression by the precursors. In conclusion, these results indicate that IFN-gamma induces CD69 expression by eosinophil precursors via the activation of JAK2.

Role of JAK2 signal transductional pathway in activation and survival of human peripheral eosinophils by interferon-gamma (IFN-gamma).

The purpose of this study was to determine whether the JAK pathway is involved in eosinophil activation and survival through IFN-gamma receptor signalling in human peripheral eosinophils. Eosinophils were purified from the blood of six atopic disease patients by anti-CD16 magnetic bead-negative selection. IFN-gamma significantly up-regulated survival and CD69 expression in 24-48 h cultured eosinophils. Further, IFN-gamma induced tyrosine phosphorylation of JAK2 in eosinophils, as indicated by Western blot analysis. Finally, the specific JAK2 inhibitor AG-490 inhibited the tyrosine phosphorylation of JAK2, IFN-gamma-induced survival and CD69 expression in eosinophils. In conclusion, these results indicate that IFN-gamma induces eosinophil survival and CD69 expression through the activation of JAK2 in peripheral eosinophils, suggesting that JAK2 may play a significant role in eosinophil regulation by IFN-gamma-IFN-gammaR interaction.

[Diagnosis of inflammatory myopathy; usefulness of 99mTc MDP scintigraphy and muscle MRI for determination of affected sites].

We studied the effectiveness of 99mTc-MDP (methylendiphosphate) scintigraphy in imaging inflammatory myopathy. The three subjects including 1 male and 2 female patients had high creatine kinase (CK) levels and proximal dominant muscle weakness. In whole body muscle surveillance by 99mTc-MDP scintigraphy, abnormal 99mTc-MDP accumulation was found in the extremities of all patients. The sites with high 99mTc-MDP accumulation showed high intensity on T2 weighted MR imaging, suggesting an inflammatory process. Muscle biopsy was performed on two patients from the muscles with the abnormal MRI findings, which showed the diagnostic finding of inflammatory changes. Because muscle involvement in inflammatory myopathy differs from muscle to muscle, it is sometimes difficult to choose appropriate muscle biopsy sites for diagnostic purposes. Affected muscles are more easily identified by using 99mTc-MDP muscle scintigraphy and muscle MRI, therefore, a correct diagnosis and choice of biopsy site can be made. 99mTc-PYP scintigraphy is permitted for use in myocardial infarction alone and 111In-antimyosin scintigraphy is not available in Japan. Therefore, we recommend 99mTc-MDP scintigraphy for diagnosis of inflammatory myopathy and for determination of muscle biopsy sites.

[The significance of Ulex europaeus agglutinin I lectin binding fibers in various muscular diseases].

In the present study, we have reported that Ulex europaeus agglutinin I (UEA I) lectin labeled muscle fibers in distal myopathy with rimmed vacuole formation (DMRV). UEA I binding to muscle fibers was also observed in a small number of biopsies with inflammatory myopathy, but not in other diseases, including neurogenic muscular atrophies and muscular dystrophies. In order to elucidate the relationship between this UEA I binding, rimmed vacuole formation and active autophagocytosis, we examined the UEA I binding fibers in other myopathies which frequently showed rimmed vacuoles, including adult onset acid maltase deficiency, oculo-pharyngo-distal type myopathy and oculopharyngeal muscular dystrophy. No UEA I lectin labeling fiber was observed in the diseases examined. We then studied UEA I binding behavior on 70 biopsies of inflammatory myopathy to characterize the clinical features of UEA I binding positive patients. UEA I binding fibers were observed in 3 of 28 patients (11%) with other collagen diseases, 11 of 36 (31%) without these disorders, and 2 of 6 (33%) with inclusion body myositis. There were no common clinical histories, complications or laboratory findings among the UEA I binding positive patients. In conclusion, a common process may exist between the muscle fiber degeneration in DMRV and subgroups of inflammatory myopathy patients, but the basic mechanism remains to be elucidated.

Glandular and extraglandular expression of the Fas-Fas ligand and apoptosis in patients with Sjögren's syndrome.

OBJECTIVE: To evaluate the role of Fas-Fas ligand system-mediated apoptosis in the sialoadenitis and interstitial nephritis of Sjögren's syndrome. METHODS: The expression of Fas antigen and Fas ligand in sialoadenitis and interstitial nephritis was examined by immunoperoxidase staining and the reverse transcriptase-polymerase reaction (RT-PCR) in patients with Sjögren's syndrome and in normal subjects. The appearance of DNA strand breaks during apoptosis was detected in the tissue by DNA nick end labeling methods. RESULTS: In patients with severe sialoadenitis, Fas antigen was strongly expressed on the ductal epithelial cells. In contrast, Fas antigen was not seen in the minor salivary glands of normal subjects nor in patients with mild sialoadenitis. In patients with massive mononuclear cell infiltration, some of the infiltrating cells showed the Fas ligand. In patients with interstitial nephritis associated with Sjögren's syndrome, Fas was expressed on the tubular epithelial cells, while such expression was not observed in control subjects without interstitial nephritis. In the patients with interstitial nephritis, some of the infiltrating cells showed the Fas ligand. Apoptotic changes were observed in the ductal epithelial cells, tubular epithelial cells and some infiltrating cells by DNA nick end labeling methods. mRNA for the Fas antigen and Fas ligand was found to be expressed in the labial salivary glands from all SS patients by RT-PCR. CONCLUSION: The findings of this study suggest that the Fas-Fas ligand system may play a role in the pathogenesis of the sialoadenitis and interstitial nephritis of Sjögren's syndrome.

Expression of cell adhesion molecules in tubulointerstitial nephritis associated with Sjögren's syndrome.

The tissue distribution of cellular adhesion molecules (ICAM-1, ELAM-1, VCAM-1) was studied in specimens from six normal human kidneys and in six biopsies from kidneys with tubulointerstitial nephritis associated with Sjögren's syndrome. In addition, the expression of cellular adhesion molecules was examined both in four renal biopsies from cases of tubulointerstitial nephritis of diverse pathogenesis and in six lip biopsies from cases of Sjögren's syndrome. ICAM-1 was expressed on vascular endothelial cells in normal kidneys, in all specimens of tubulointerstitial nephritis and in salivary glands. On tubular epithelial cells, ICAM-1 appeared slightly in normal kidneys; otherwise tubular epithelial ICAM-1 was observed in and around the foci of cellular infiltration in all cases of tubulointerstitial nephritis. ELAM-1 and VCAM-1 were observed on the newly generated vessels in massive cellular infiltrates in some cases of tubulointerstitial nephritis associated with Sjögren's syndrome; by contrast, they were not seen in normal kidneys and in cases of tubulointerstitial nephritis of diverse pathogenesis. In the lip biopsies from salivary glands, ICAM-1 was observed on ductal epithelial cells in and around the foci of cellular infiltration, and ELAM-1 and VCAM-1 occasionally appeared on the newly generated vessels in massive cellular infiltrates. Chronic and progressive inflammation may be facilitated by such ELAM-1 and VCAM-1 expression on newly generated vessels. The adhesion molecules were thought to play a role in the pathogenesis of tubulointerstitial nephritis and sialoadenitis associated with Sjögren's syndrome. It was thus concluded that the same inflammatory process that took place in the salivary glands to induce the characteristic tissue change of Sjögren's syndrome likely was operative in the renal tubulointerstitial tissue as well.

[Focal segmental glomerulosclerosis presenting nephrotic syndrome and acute renal failure in a patient with rheumatoid arthritis].

A 45-year-old woman with rheumatoid arthritis(RA) who developed nephrotic syndrome and acute renal failure was reported. She first noticed polyarthritis in June 1990, and was diagnosed as RA. Since her RA was not controlled with nonsteroidal anti-inflammatory drugs (NSAID), she started taking prednisolone 10 mg daily and received 100 mg of D-penicillamine from October 1990 with improvement of the RA. In March 1991, she noticed edema of the face and legs, at which time massive proteinuria and hematuria were first noted. Because of her nephrosis, she was referred to our hospital for further evaluation. Laboratory investigations revealed 24-hour urine proteinuria of 37 g, serum creatinine, 2.7 mg/dl, blood urea nitrogen, 43.5 mg/dl, total protein, 4.1 g/dl, albumin, 1.5 mg/dl, and total cholesterol, 600 mg/dl. The rheumatoid factor and anti-nuclear antibody were positive. Renal biopsy showed focal segmental glomerulosclerosis (FSGS). Her nephrotic syndrome and renal dysfunction recovered after the administration of prednisolone at 60 mg/day. The possible pathogenesis of FSGS in patients with RA was discussed.

[Diffuse proliferative lupus nephritis in a patient with ulcerative colitis].

A 31 year-old man treated with sulfasalazine for ulcerative colitis, developed nephrotic syndrome, photosensitivity, alopecia, lymphopenia and hypocomplementemia. Anti-nuclear antibody (speckled) and antibodies to single-stranded DNA and SS-A were positive, while those against native DNA and histon were negative. Renal biopsy revealed diffuse proliferative lupus nephritis. His nephrotic syndrome partially improved with corticosteroid therapy combined with cessation of sulfasalazine. His complement level became normal, however it decreased again during the gradual reduction of corticosteroid dosage. In conclusion, we diagnosed the patient's illness as an idiopathic syntemic lupus erythematosus rather than sulfasalazine-induced lupus.

Expression of ductal Fas antigen in sialoadenitis of Sjögren's syndrome.

OBJECTIVE: The expression of Fas antigen on ductal epithelial cells of sialoadenitis was examined in patients with Sjögren's syndrome (SS) and in normal subjects. METHODS: Minor salivary glands from the SS patients were examined by an immunohistochemical method using a new monoclonal antibody to the Fas antigen. RESULTS: In two patients with severe sialoadenitis, Fas was strongly expressed on the ductal epithelial cells. By contrast, the Fas antigen was not seen in the minor salivary glands of normal subjects nor in those with mild sialoadenitis. CONCLUSION: This finding suggests that the Fas antigen may play a role in the pathogenesis of sialoadenitis in SS by providing a specific target for cytotoxic T cells expressing the Fas ligand.

[Expression of ductal Fas antigen in sialoadenitis of Sjögren's syndrome].

The expression of Fas antigen on ductal epithelial cells of sialoadenitis was examined in patient with Sjögren's syndrome and normal subject. In two patients with severe sialoadenitis, Fas antigen was strongly expressed on the ductal epithelial cells. In contrast, Fas antigen was not seen in minor salivary gland of normal subjects and of mild sialoadenitis cases. This finding suggests that Fas antigen may play a role in the pathogenesis of sialoadenitis in Sjögren's syndrome by providing a specific target for cytotoxic T cells expressing Fas ligand.