RESUMEN
Salivary gland epithelial cells (SGECs) have been implicated in the pathogenesis of Sjögren's syndrome due to aberrant antigen-presentation function. This study examined the hypothesis that oral dysbiosis modulates the antigen-presentation function of SGECs, which regulates CD4 T cell proliferation in primary Sjögren's syndrome (pSS). Saliva samples from 8 pSS patients and 16 healthy subjects were analyzed for bacterial 16S ribosomal DNA. As a result, 39 differentially abundant taxa were identified. Among them, the phylum Proteobacteria comprised 21 taxa, and this phylum was mostly enriched in the healthy controls. The proteobacterium Haemophilus parainfluenzae was enriched in the healthy controls, with the greatest effect size at the species level. Treatment of A253 cells in vitro with H. parainfluenzae upregulated PD-L1 expression, and H. parainfluenzae-pretreated A253 cells suppressed CD4 T cell proliferation. The suppression was partially reversed by PD-L1 blockade. Among low-grade xerostomia patients, salivary abundance of H. parainfluenzae decreased in pSS patients compared to that in non-pSS sicca patients. Our findings suggest that H. parainfluenzae may be an immunomodulatory commensal bacterium in pSS.
Asunto(s)
Disbiosis/diagnóstico , Haemophilus parainfluenzae/inmunología , ARN Ribosómico 16S/genética , Saliva/microbiología , Glándulas Salivales/citología , Análisis de Secuencia de ADN/métodos , Síndrome de Sjögren/microbiología , Anciano , Presentación de Antígeno , Linfocitos T CD4-Positivos/metabolismo , Estudios de Casos y Controles , Línea Celular , Proliferación Celular , ADN Bacteriano/genética , ADN Ribosómico/genética , Células Epiteliales/citología , Células Epiteliales/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Glándulas Salivales/inmunología , Glándulas Salivales/microbiología , Síndrome de Sjögren/inmunologíaRESUMEN
Hemolytic uremic syndrome (HUS) is not a commonly reported complication in post-transplantation patients treated with cyclosporine-A (CSA), and is extremely rare in systemic sclerosis (SSc) patients treated with this drug. CSA may contribute to the development of chronic ischemic glomerulonephropathy and vasculopathy, features not easily distinguished from SSc-related nephropathy. Here, we describe a 41-year-old Chinese man with diffuse-type SSc treated with CSA who developed thrombocytopenia, acute renal failure and hemolytic anemia and was diagnosed with HUS. Renal function and thrombocytopenia improved gradually after intensive treatment of plasma exchange (PE) and high-dose steroid therapy. After PE, renal biopsy showed ischemic glomerulonephropathy and obliterative vasculopathy. This case illustrates that PE can improve the hematological disorders and characteristic renal changes of HUS in SSc patients treated with CSA. However, this therapy may not be effective in normalizing serum creatinine level in SSc patients once CSA has triggered the normal kidney to develop glomerulonephropathy and vasculopathy with ischemic and sclerotic changes.
Asunto(s)
Ciclosporina/efectos adversos , Glomerulonefritis Membranosa/inducido químicamente , Síndrome Hemolítico-Urémico/inducido químicamente , Isquemia/inducido químicamente , Esclerodermia Sistémica/tratamiento farmacológico , Vasculitis/inducido químicamente , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/fisiopatología , Adulto , Anemia Hemolítica/inducido químicamente , Anemia Hemolítica/fisiopatología , Antirreumáticos/efectos adversos , Pueblo Asiatico , Creatinina/sangre , Glomerulonefritis Membranosa/fisiopatología , Síndrome Hemolítico-Urémico/fisiopatología , Humanos , Isquemia/fisiopatología , Riñón/irrigación sanguínea , Riñón/efectos de los fármacos , Riñón/patología , Masculino , Intercambio Plasmático , Arteria Renal/efectos de los fármacos , Arteria Renal/patología , Arteria Renal/fisiopatología , Esteroides/uso terapéutico , Taiwán , Trombocitopenia/inducido químicamente , Trombocitopenia/fisiopatología , Vasculitis/fisiopatologíaRESUMEN
Mycobacterium-associated lobular panniculitis can mimic a rheumatoid nodule and has been seldom reported in rheumatoid arthritis (RA). We describe a 69-year-old woman with RA who presented initially with fever and an indurated skin lesion on the right thigh. Lobular panniculitis was diagnosed after biopsy and was then treated with prednisolone. After this therapy, pulmonary infiltration developed and was later shown by transbronchial biopsy to be caused by Mycobacterium tuberculosis. The panniculitis skin lesion became smaller after prednisolone therapy and was further improved after antituberculosis drugs were added. Reexamination of the previously biopsied skin tissue disclosed acid-fast bacilli. Reactivation or new infection of M. tuberculosis is a current important issue in RA patients, especially after treatment with disease-modifying anti rheumatic drugs or antitumor necrosis factor agents. Mycobacterium-associated lobular panniculitis should be included in the differential diagnosis of indurated skin disorder in RA patients, and acid-fast staining or polymerase chain reaction examination of tuberculosis should be performed routinely on biopsied skin tissue.
Asunto(s)
Artritis Reumatoide/complicaciones , Paniculitis/diagnóstico , Nódulo Reumatoide/diagnóstico , Tuberculosis/complicaciones , Anciano , Femenino , Humanos , Paniculitis/patologíaRESUMEN
BACKGROUND: To understand the cytokine levels in different disease activities of patients with ankylosing spondylitis (AS), we measured proinflammatory and antiinflammatory cytokine production from peripheral blood mononuclear cells (PBMC) in patients with AS and their first-degree relatives (FDR). METHODS: PBMC were obtained from 26 patients with AS and 24 FDR and then stimulated with PHA for 72 h. In the supernatants, the following three cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), and IL-10, were measured by ELISA. Disease activity in AS patients was divided into high disease activity (Group 1) and low disease activity (Group 2), based on the Bath AS Disease Activity Index (BASDAI > or =4 or <4). Healthy FDR of AS patients (Group 3) and healthy subjects (Group 4) were used as a control group. RESULTS: TNF-alpha production from PBMC was significantly increased in Group 1 patients compared to Group 2 patients (1371 +/- 1008 pg/mL vs. 355 +/- 89 pg/mL, p <0.05) or FDR (1371 +/- 1008 pg/mL vs. 552 +/- 89 pg/mL, p <0.05) or healthy subjects (1371 +/- 1008 pg/mL vs. 436 +/- 114 pg/mL, p <0.01). IL-1beta also showed a similarly significant difference between the two groups (Group 1 vs. Group 2, Group 1 vs. Group 4) (p <0.05). In contrast, IL-10 was significantly decreased in Group 1 when compared to Group 2 (126 +/- 64 pg/mL vs. 272 +/- 150 pg/mL, p <0.05). CONCLUSIONS: Patients with high BASDAI had increased production of TNF-alpha and IL-1beta compared to those with low BASDAI or healthy FDR, suggesting that proinflammatory cytokines may play an important role during active inflammation.
Asunto(s)
Citocinas/análisis , Leucocitos Mononucleares/inmunología , Espondilitis Anquilosante/diagnóstico , Adolescente , Adulto , Citocinas/biosíntesis , Salud de la Familia , Femenino , Humanos , Masculino , Índice de Severidad de la Enfermedad , Espondilitis Anquilosante/inmunologíaRESUMEN
Autoimmune inner ear disease (AIED) is a very rare disorder with distinct clinical features and can occur in patients with malignancy or autoimmune diseases. We report a 72-year-old male patient with polyarteritis nodosa treated continuously for 5 years with aggressive immunosuppressive drugs, including cyclophosphamide, who experienced three episodes of acute hearing loss during treatment. Organic lesions of the external and middle ear were excluded by repeated examinations, and if one subscribes to McCabe's (Ann Otol Rhinol Laryngol 88:585-589, 1979) definition of AIED, this condition must be considered as the likely cause of the hearing loss. During the period of treatment, three episodes of AIED occurred, and eventually, lung cancer developed. From the time relationship and clinical manifestations of neuropathy and livedo reticularis, the first episode of hearing loss was more likely to be related to vasculitis itself, while the third episode may well have been associated with the development of lung cancer given the dramatic improvement in the clinical condition following treatment of the tumor by excision and cancer chemotherapy. Coexistence of AIED, vasculitis, and malignancy in the same patient has only been reported infrequently, and our case suggests that this coexistence may not be coincidental. For those patients with autoimmune disease who are on long-term immunosuppressive drug therapy, active surveillance for a nascent malignant tumor should be exercised if AIED recurs or persists.
Asunto(s)
Enfermedades Autoinmunes/complicaciones , Carcinoma de Células Grandes/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Enfermedades del Laberinto/inmunología , Neoplasias Pulmonares/complicaciones , Poliarteritis Nudosa/complicaciones , Anciano , Enfermedades Autoinmunes/diagnóstico , Pérdida Auditiva Súbita/etiología , Humanos , Enfermedades del Laberinto/complicaciones , Enfermedades del Laberinto/diagnóstico , Masculino , Poliarteritis Nudosa/tratamiento farmacológico , RecurrenciaRESUMEN
Acute anterior uveitis (AAU) is the most frequently extra-articular manifestation of ankylosing spondylitis (AS). To investigate whether AAU has an association with disease activity, functional ability and physical mobility in AS patients, 146 Chinese AS patients in Taiwan were enrolled in a cross-sectional study. These patients fulfilled the 1984 modified New York criteria and visited the Outpatient Department of the Veterans General Hospital-Taipei from April 2004 to July 2005. Patients completed questionnaires assessing disease activity [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)], functional ability [Bath Ankylosing Spondylitis Functional Index (BASFI)] and patient's global assessment [Bath Ankylosing Spondylitis Patient Global Score (BAS-G)]. Meanwhile, physical examinations were performed, including Schober test, finger-to-floor, lateral spinal flexion, occiput-to-wall and chest expansion. The history of AAU was accepted only if diagnosed by an ophthalmologist. The prevalence of AAU in this Chinese AS cohort was 15.8% (23/146). Patients with AAU had a significantly higher BASDAI than those without [absolute differences=0.96, 95% confidence intervals (CI): 0.35-1.88]. Additionally, patients with AAU had significantly increased BASFI than those without (absolute differences=1.46, 95% CI: 0.33-2.59). Moreover, there was advanced limitation of physical motility in patients with AAU, including finger-to-floor, occiput-to-wall distances and Schober test, (95% CI: 3.89-16.95 and p=0.046, respectively). Disease duration mildly correlated with BASFI (r=0.24, p=0.003) but not with BASDAI (p=0.838). There was no difference of disease duration between patients with and without AAU (p=0.343). These results suggested that the presence of AAU in AS patients may be associated with higher disease activity, poor functional ability and advanced physical impairment.
Asunto(s)
Actividades Cotidianas , Espondilitis Anquilosante/complicaciones , Uveítis Anterior/complicaciones , Enfermedad Aguda , Adulto , China/etnología , Estudios Transversales , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Índice de Severidad de la Enfermedad , Espondilitis Anquilosante/etnología , Estadísticas no Paramétricas , Taiwán/epidemiología , Uveítis Anterior/epidemiología , Uveítis Anterior/etnologíaRESUMEN
A 79-year-old male with acute myelogenous leukemia developed acute right knee arthritis during admission, after the use of broad-spectrum antibiotics before chemotherapy. The initial synovial fluid sample appeared to be mildly inflammatory with a low white cell count. The fungal septic arthritis was not diagnosed until Candida tropicalis, a rare species of Candida, was isolated in the synovial fluid. Although fluconazole is effective in treating the microorganism, the untreated leukemia rendered the infection incurable and led to the growth of fluconazole-resistant Candida krusei. We reported the unusual case of fungal arthritis and reviewed the literature.
Asunto(s)
Artritis Infecciosa/patología , Candida/aislamiento & purificación , Candidiasis/patología , Leucemia Mieloide Aguda/patología , Anciano , Antifúngicos/uso terapéutico , Artritis Infecciosa/microbiología , Candidiasis/complicaciones , Candidiasis/tratamiento farmacológico , Resultado Fatal , Fluconazol/uso terapéutico , Humanos , Leucemia Mieloide Aguda/microbiología , Masculino , Líquido Sinovial/microbiologíaRESUMEN
BACKGROUND: Undifferentiated spondyloarthropathy (USpA) is a unique group in spondyloarthropathy (SpA). This study will investigate the clinical and laboratory characteristics of USpA in the Chinese population. METHODS: Forty two patients with USpA were enrolled from our rheumatology outpatient facility in this retrospective study. SpA was diagnosed according to the European Spondyloarthropathy Study Group (ESSG) criteria. Patients were considered having USpA when they had SpA but did not meet the criteria for the diagnosis of ankylosing spondylitis (AS), Reiter's syndrome or reactive arthritis (ReA), psoriatic arthritis (PsA), and inflammatory bowel diseases (IBD)-related arthritis, etc. Laboratory tests included erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), immunoglobulin A (IgA), and human leukocyte antigen B27 (HLA-B27). RESULTS: Among the 42 USpA patients, the ratio of men to women was 1.47:1, and the age at onset was 32.33 +/- 10.83 years old. Approximately 61.9% of patients had peripheral arthritis, 30.95% had uveitis, and 64.29% had positive HLA-B27. Among these female USpA patients, compared to males, there is a trend of older age at disease onset, higher percentage of HLA-B27 positive, more peripheral arthritis and uveitis, longer disease duration, and higher level of ESR, and IgA and CRP in serum. The items reaching significant difference between males and females were longer disease duration (p < 0.001), higher level of ESR (p < 0.001), and serum IgA (p = 0.03). There was no significant difference in clinical and laboratory characteristics between HLA-B27-positive and -negative groups. CONCLUSIONS: Studies on USpA patients have not been reported in the Chinese population. In this study, we demonstrate the unique demographic characteristics, clinical and laboratory data of USpA in the Chinese population. These findings should be confirmed by analyzing larger number of patients and longer time for further follow-up. Such studies are crucial to understand the pathogenesis of USpA and evaluate its prognosis.
Asunto(s)
Espondiloartropatías/diagnóstico , Espondiloartropatías/patología , Adulto , China , Femenino , Antígeno HLA-B27/metabolismo , Humanos , Masculino , Prohibitinas , Estudios Retrospectivos , Caracteres Sexuales , Espondiloartropatías/metabolismoAsunto(s)
Calcinosis/etiología , Carcinoma de Células Grandes/complicaciones , Dermatomiositis/complicaciones , Neoplasias Pulmonares/complicaciones , Calcinosis/diagnóstico por imagen , Carcinoma de Células Grandes/diagnóstico por imagen , Carcinoma de Células Grandes/patología , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Radiografía , Enfermedades de la Piel/diagnóstico por imagen , Enfermedades de la Piel/etiologíaRESUMEN
Evidence have indicated the impairment of central nervous system (CNS) and neuropsychiatric disorder in patients with systemic lupus erythematosus (SLE). However, little is known to improve the brain abnormality in SLE. To investigate the effect of cystamine on brain abnormality in SLE, NZB/W F1 mice were used as the animal model. Notably, significantly reduced neural Nitric Oxide Synthase (nNOS), inducible Nitric Oxide Synthase (iNOS), p53, p21(WAF1/CIP1), and heat shock protein (HSP)-90 proteins were detected in the brain of NZB/W F1 mice that were treated with cystamine. In contrast, no variation was observed between the brain samples of BALB/c mice that were treated with PBS or cystamine. Moreover, significantly reduced Toll-like receptors- (TLR-) 4, 5 and 7 were detected in the brain samples of NZB/W F1 mice that were treated with cystamine whereas no variation of TLR-4, TLR-5, TLR-7, and TLR-9 was observed in BALB/c mice that were treated with PBS or cystamine. These findings demonstrated the beneficial effects of cystamine on brain abnormality in NZB/W F1 mice and probably suggested the potential of cystamine on treating patients with neuropsychiatric SLE.
Asunto(s)
Cistamina/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Receptores Toll-Like/efectos de los fármacos , Animales , Encéfalo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/efectos de los fármacos , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Modelos Animales de Enfermedad , Femenino , Proteínas HSP90 de Choque Térmico/efectos de los fármacos , Proteínas HSP90 de Choque Térmico/metabolismo , Lupus Eritematoso Sistémico/fisiopatología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos NZB , Óxido Nítrico Sintasa de Tipo I/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo I/metabolismo , Óxido Nítrico Sintasa de Tipo II/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II/metabolismo , Receptores Toll-Like/genética , Proteína p53 Supresora de Tumor/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
OBJECTIVE: Sjögren's syndrome (SS) is an inflammatory autoimmune disease. We investigated important factors associated with the expression of inflammation-related molecules in minor salivary gland (MSG) mononuclear cells in patients with SS. METHODS: Thirty-four patients with SS with a MSG biopsy grading of either grade III (10 patients) or grade IV (24 patients) were enrolled. The age, sex, autoantibodies, cell infiltration, and intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase-3 (MMP-3), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), or CXCR3 expression were also analyzed. RESULTS: Ten of the 34 patients with SS were diagnosed with secondary SS; in these patients, the diagnosis of rheumatoid arthritis was confirmed in 8 and systemic lupus erythematosus in 2. TRAIL and ICAM-1 were overexpressed in patients with antinuclear antibodies (ANA) > 1:160, compared to those with titer < 1:160 (45.1 +/- 4.4 vs 41.2 +/- 3.9, p = 0.021, and 15.2 +/- 5.7 vs 10.8 +/- 3.3, p = 0.018, respectively). Higher erythrocyte sedimentation rate (ESR; >OR= 20) was associated with higher TRAIL expression and CD20 cell infiltration in contrast to lower ESR (< 20; p < 0.05). ICAM-1, TRAIL, and MMP-3 were expressed more predominantly in anti-SSA-positive than in anti-SSA-negative patients with SS. There was a significant difference in CD20 cell infiltration and MMP-3 expression between primary SS and secondary SS. Biopsy of a grade IV showed a significantly increased expression of TRAIL (44.9 +/- 4.5 vs 40.8 +/- 3.6, p = 0.013) and MMP-3 (62.7 +/- 6.3 vs 54.4 +/- 7.3, p = 0.003) in mononuclear cells as compared to those of grade III. CONCLUSION: In our study, pathologic grading with a higher grade (grade IV) and the presence of SSA or a higher titer of ANA were significantly associated with the overexpression of TRAIL, MMP-3, or ICAM-1 in the salivary gland mononuclear cells in patients with SS.