Published papers

Objective. To determine the diagnostic value in Sjögren's syndrome (SS) of evaluating the presence of focal adenitis in labial salivary gland (LSG) and lacrimal gland (LG) biopsy specimens. Methods. We studied 105 cases with suspected SS and performed biopsies prospectively. The diagnostic criteria of Fox, et al were followed. The Chisholm-Mason grading standard and Greenspan focus score were used for evaluation. Results. Epimyoepithelial islands and severe lymphocyte infiltration with germinal centers were observed only in LG biopsy specimens (5.9 and 3.5%, respectively). The lymphocytic focus scores of LG (2.5 ± 2.1/4 mm2) were significantly higher than those of LSG specimens (1.3 ± 1.1/4 mm2) in 23 cases with both biopsy results (p < 0.05). Six of the 32 LSG biopsies were normal while their LG biopsies were significantly higher. Conversely, 5 of the 32 LG biopsies were aided by corresponding LSG biopsies, since in LG biopsies no glandular tissue was obtained. Evaluation of both specimens for the same patient was significantly more effective in diagnosing SS than using either specimen alone (p < 0.01). Conclusion. LG biopsy specimens have a more evident histopathology than LSG biopsy specimens. We recommend that both LSG and LG biopsies be performed in patients with suspected SS to reduce false negative results and improve diagnostic accuracy.

Objective. To investigate whether reflex tearing measured by the Schirmer test with nasal stimulation is better correlated with lymphocytic infiltration of the lacrimal gland and is thus a more appropriate test for Sjogren's syndrome (SS). Methods. 272 patients with dry eye (age 55.5 ± 13.5 years) with regular Schirmer test results <10 mm were recruited for the study. They were divided into 2 groups depending on the results of the Schirmer test with nasal stimulation. 24 age and sex matched patients from each group were selected for lacrimal gland biopsy and 10 patients for salivary gland biopsy, and the levels of systemic autoantibodies and degrees of ocular surface staining and lymphocytic infiltration of the lacrimal and salivary glands were compared. Results. Of the 272 patients, 187 (68.8%) had good reflex tearing (GT) and 85 (31.2%) had poor reflex tearing (PT). There were no significant differences in the age or sex of the 2 groups. Lymphocytic infiltration of the lacrimal gland was observed in 7 GT cases and 22 PT cases out of 24 cases. Lymphocytic infiltration of the salivary gland was also higher in the PT (6 of 10) than the GT group (2 of 10). Conclusion. Evaluation of reflex tearing by the Schirmer test with nasal stimulation identifies 2 groups of patients with dry eye. Those with poor reflex tearing were more likely to have autoantibodies and lymphocytic infiltration of the exocrine glands consistent with SS.

We measured interleukin-4 (IL-4) and IgE to study their presence in patients with seasonal allergic conjunctivitis. Twenty patients and 10 normal subjects were enrolled in this study, and their brush cytology samples and peripheral blood lymphocytes (PBL) were cultured for 3 or 24 h. IL-4 levels were measured using ELISA in the supernatants. Measurements of serum IgE were also performed. IL-4 was detected in 4 of 40 brush cytology samples and 10 of 40 PBL samples, but not from the controls. IL-4 positivity rate of patients was significantly higher than normal in 24-hour cultured PBL (p = 0.03). Patients' serum IgE was also significantly higher (p = 0.006). IL-4 may contribute to the development of seasonal allergic conjunctivitis.

We report a polymyositis patient who developed Candida pneumonia, whose clinical manifestations such as dry cough, dyspnea, fever and elevated LDH looked like a recurrence of interstitial pneumonitis (IP) which she had had at admission. The distribution of the lesions in high resolution computed tomography scan, the high serum level of β-D-glucan and positive Candida antigen test led to make a diagnosis of Candida pneumonia rather than IP, and fluconazole therapy was successful.

Purpose: To compare conjunctival epithelium expression of HLA-DR and ICAM-1 with tear dynamics and ocular surface parameters. Methods: Brush cytology and flow cytometry were used to quantitatively analyze HLA-DR and ICAM-1 expression in 28 dry eye patients. Results: HLA-DR was expressed in 66% of the conjunctival cells of dry eye patients. This expression correlates with that of ICAM-1, as well as with the Schirmer test results (p<0.05). Conclusion: This study confirmed that dry eye consists not only of ocular surface desiccation, but also of upregulation of the HLA-DR and ICAM-1 molecule in the conjunctival epithelium, possibly resulting in increased inflammation.

Purpose. To demonstrate that interferon-γ (IFN-γ) is the key cytokine responsible for the upregulation of HLA-DR antigen in conjunctival epithelial cells of Sjogren syndrome (SS) patients. Methods. Flow cytometry of conjunctival epithelial cells from SS and non-SS dry eye patients was performed for the quantification of HLA-DR surface expression. With a conjunctival epithelial cell line (ChWK), HLA-DR regulation by various cytokines was evaluated, and confocal immunocytochemical and western blot analyses were performed to evaluate the activation of nuclear factor-kappa B (NF-κB) and signal transducers and activators of transcription 1 and 3 (STAT1 and STAT3, respectively). Results. HLA-DR expression was upregulated in conjunctival epithelial cells of SS patients but not in non-SS dry eye patient or healthy control subject. IFN-γ was the only cytokine that effectively upregulated HLA-DR expression in ChWK, which was synergistically enhanced by tumor necrosis factor-α (TNF-α). IFN-γ induced the nuclear translocation of NF-κB, but did not activate STAT1 or STAT3 in ChWk. Conclusions. Upregulation of HLA-DR antigen in the conjunctival epithelium of SS patients may be regulated by IFN-γ through the activation of NF-κB.

We report two cases of polymyositis (PM) complicated with nosocomial pneumonia probably caused by Stenotrophomonas maltophilia, which was resistant to multiple antimicrobials. In the first case, the chest CT findings and high serum endotoxin level as well as sputum culture results were helpful for the proper diagnosis and the therapy was successful. However the second patient died of a lung abscess in spite of the intensive antibiotic therapy. When PM patients develop pneumonia unresponsive to various antibiotics, a multi-drug-resistant bacteria such as Stenotrophomonas maltophilia should be considered as the pathogen.

The T lymphocytes that infiltrate the exocrine glands in Sjogren's syndrome (SS) play a key role in damaging glandular epithelial cells, but the mechanisms of tiffs damage by T lymphocytes are not fully understood. To determine the cellular basis of this phenomenon, we focused our attention on the T lymphocytes around acinar epithelial cells in SS. We showed that CD8+ but not CD4+ T lymphocytes were located around the acinar epithelial cells and that a majority of these CD8+ T lymphocytes possess an unique integrin, α(E)β7 (CD103). The acinar epithelial cell adherent with α(E)β7 (CD103)+ CD8+ T lymphocytes was apoptotic. Both the perforin/granzyme B and Fas/Fas ligand pathways were implicated in the process of programmed cell death in lacrimal glands. These results suggested that α(E)β7 integrin, by interacting with E-cadherin, mediates the adhesion between CD8+ T lymphocytes and acinar epithelial cells in SS and participates in inducing epithelial cell apoptosis, leading to secretory dysfunction of exocrine glands, a hallmark of SS.

To address the molecular mechanism underlying the functional defects of peripheral T cells in systemic lupus erythematosus (SLE), we focused on early signaling events. We demonstrated that protein expression of the TCR ζ chain was significantly decreased in peripheral T cells from patients with SLE compared to normal controls and patients with systemic sclerosis (SSc). Among those patients showing decreased TCR ζ chain expression, we found two patients with pronounced TCR ζ chain abnormalities, including an aberrant 14 kDa form in one and only trace expression in the other. RT-PCR, SSCP and subsequent cloning of the transcripts revealed that bases 468-503, corresponding to exon 7, were deleted in both patients. Since exon 7 spans the GTP/GDP binding site and N-terminal tyrosine in the third ITAM domain of TCR ζ chain, the transcript lacking exon 7 may be responsible for altered signal transduction via TCR in these SLE patients.