Assessment of peripheral blood CD4+ adenosine triphosphate activity in patients with rheumatoid arthritis.

OBJECTIVE: The ability of the ImmuKnow (Cylex) assay to predict the risk of infection in rheumatoid arthritis (RA) patients receiving synthetic or biological disease-modifying antirheumatic drugs (DMARDs) was examined. METHODS: The amount of adenosine triphosphate (ATP) produced by CD4+ cells in response to phytohemagglutinin was measured in whole blood from 117 RA patients without infection versus 17 RA patients with infection, and compared with results in 75 healthy controls. RESULTS: The mean ATP level was significantly lower in patients with infection compared to both healthy controls (P < 0.0005) and patients without infection (P = 0.040). Also, the mean ATP level in patients without infection was significantly lower than that in healthy controls (P = 0.012). There was no correlation between the ATP level and the Disease Activity Score in 28 joints. CONCLUSION: ImmuKnow assay results may be effective in identifying RA patients at increased risk of infection, but the results showed no correlation with RA activity. Larger studies are required to establish the clinical advantages of this assay in RA treatment.

Target epitopes of HTLV-1 recognized by class I MHC-restricted cytotoxic T lymphocytes in patients with myelopathy and spastic paraparesis and infected patients with autoimmune disorders.

Human T-cell lymphotropic virus type I (HTLV-1) causes adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The different patterns of clinical diseases are thought to be linked to immunogenetic host factors. A variety of autoimmune diseases, such as Sjögren's syndrome, have been reported in persons infected with HTLV-1, although the precise relationship between these disorders and HTLV-1 infection remains unknown. There is no report on the repertoire of HTLV-1-specific CD8+ T-cells in HAM/TSP patients or carriers with autoimmune diseases, both characterized by an abnormal immune state. In this study, to characterize HTLV-1-specific CD8+ T-cells in asymptomatic HTLV-1 carriers, HAM/TSP patients and carriers with autoimmune diseases, we examined the frequency and diversity of HTLV-1-specific CD8+ T-cells using HTLV-1 tetramers. HTLV-1 Env-specific CD8+ T-cells were significantly more frequent in HAM/TSP and carriers with autoimmune diseases compared with asymptomatic HTLV-1 carriers, while the frequency of HTLV-1 Tax-specific CD8+ T-cells was not significantly different among them. CD8+ cells binding to HTLV-1 Tax tetramers in carriers with autoimmune diseases were significantly reduced compared with HAM/TSP patients. This study demonstrates the importance of CD8+ T-cells recognizing HTLV-1 Env-tetramers in HAM/TSP patients and carriers with autoimmune diseases, thereby suggesting that the diversity, frequency and repertoire of HTLV-1 Env-specific CD8+ T-cell clones may be related to the hyperimmune response in HAM/TSP and carriers with autoimmune diseases, although different immunological mechanisms may mediate the hyperimmunity in these conditions.

Clinical manifestations of human T lymphotropic virus type I-infected patients with systemic lupus erythematosus.

OBJECTIVE: Human T lymphotropic virus type I (HTLV-I) may be associated with some connective tissue autoimmune diseases, including systemic lupus erythematosus (SLE). To determine the relationship between HTLV-I infection and SLE, we examined the clinical manifestations of SLE patients with HTLV-I infection. METHODS: Eighty-nine patients with SLE were screened for antibodies to HTLV-I by electrochemiluminescence immunoassay. The presence of HTLV-I proviral sequences in peripheral blood mononuclear cells (PBMC) was determined by real-time polymerase chain reaction (PCR) quantification and Southern blotting analysis. The differences in clinical manifestations between HTLV-I-seropositive and seronegative patients with SLE were analyzed statistically. RESULTS: Fourteen of 89 (15.7%) patients were HTLV-I seropositive. All PBMC samples from 11 patients tested by PCR and 3 samples from 10 patients tested by Southern blotting analysis were positive for HTLV-I-related sequences. The age of HTLV-I-seropositive patients with SLE was significantly higher than that of seronegative patients (median 60 vs 42 yrs; p < 0.0005). The age at onset of SLE in HTLV-I-seropositive patients was also significantly higher than that of seronegative patients (median 45.5 vs 30 yrs; p <0.0005). The lymphocyte count in HTLV-I-seropositive SLE patients was significantly higher than that of seronegative patients (median 1740 vs 1066/microl; p = 0.027). The maintenance dose of prednisolone in HTLV-I-seropositive patients with SLE was significantly lower than that in seronegative patients (median 5 vs 9 mg/day; p = 0.012). CONCLUSION: This is the first report of the differences in clinical manifestations between SLE patients with and without HTLV-I infection. Our results suggest some involvement of HTLV-I in the pathogenesis of SLE.

Stevens-Johnson syndrome induced by mizoribine in a patient with systemic lupus erythematosus.

A 32-year-old Japanese woman, who had a treatment history of systemic lupus erythematosus (SLE) with lupus nephritis World Health Organization class IV for 11 months, visited our hospital due to fever, facial erythema, and erosion of the oral cavity on November 10, 2003. Her mucosal erosion and facial skin erythema progressed over the following week, and Stevens-Johnson syndrome was diagnosed due to pathological findings of the skin. Among the administrated drugs, only mizoribine, started 6 months earlier, produced a positive reaction in the drug lymphocyte stimulation test. Increased prednisolone and high dose intravenous gamma-globulin were given successfully. Cyclosporine at 50 mg was administered to control the SLE, followed by an increase to 100 mg on January 7, 2004. She suffered from abdominal pain, blindness, and convulsion on January 9. The magnetic resonance image of her brain prompted a diagnosis of reversible posterior leukoencephalopathy syndrome. After withdrawal of cyclosporine and control of hypertension, symptoms disappeared rapidly. Cyclophosphamide pulse therapy was successfully administrated to control lupus nephritis. This is the first report describing the relationship between Stevens-Johnson syndrome and mizoribine. Although the use of mizoribine is thought to be safe, careful observation is necessary.

Interferon-alpha therapy following autologous peripheral blood stem cell transplantation for adult T cell leukemia/lymphoma.

In the present report, we describe a case of adult T cell leukemia/lymphoma (ATLL), a 58-year-old woman, successfully treated with interferon (IFN)-alpha following autologous peripheral blood stem cell transplantation (auto-PBSCT). The patient remains in remission with full performance status for more than 12 months. Auto-PBSCT reduced the abdominal lymphoma mass and IFN-alpha eliminated residual tumor cells, possibly through the induction of specific T-cell subsets expressing CD3, CD8 on their surfaces and either IFN-gamma or tumor necrosis factor (TNF)-alpha in cytoplasm. We have treated a total of 4 ATLL patients with auto-PBSCT, including the case presented herein. All other patients treated with auto-PBSCT were not followed by adjuvant chemotherapy or cytokine therapy and relapsed within 3 months after auto-PBSCT. This evidence suggests that the therapeutic success of the present case was attributable to the administration of IFN-alpha immunotherapy following auto-PBSCT.