RESUMEN
OBJECTIVES: We aimed to assess the clinical features of human T-cell leukaemia virus type 1 (HTLV-1)-positive rheumatoid arthritis (RA) patients. Furthermore, we investigated the impact of HTLV-1 infection on incidences of serious infections requiring hospitalisation (SIH) and malignancies. METHODS: A total of 150 sex- and age-matched HTLV-1-negative and 50 HTLV-1-positive RA patients were enrolled from the HTLV-1 RA Miyazaki Cohort Study. Clinical and laboratory data were collected from this cohort database. The incidence rate (IR) for SIH and malignancies from 2015 to 2020 was analysed. RESULTS: The median age and female ratio in the study population were 70 years old and 80%, respectively. Although no differences were found in inflammatory marker values between the two groups, the patient global assessment and Health Assessment Questionnaire scores were higher in HTLV-1-positive RA patients. In HTLV-1-negative RA patients, the IR for SIH was 6.37/100 person-years (PY) and 1.32/100 PY for malignancies. In HTLV-1-positive RA patients, SIH occurred in 11.1/100 PY and malignancies in 2.46/100 PY. The crude IR ratio comparing SIH between two groups was 1.74 (95% confidence interval, 1.04-2.84), which was a significant increase. CONCLUSIONS: HTLV-1-positive RA patients may worsen RA symptoms. HTLV-1 may be a risk factor for SIH.
Asunto(s)
Artritis Reumatoide , Virus Linfotrópico T Tipo 1 Humano , Leucemia de Células T , Anciano , Artritis Reumatoide/epidemiología , Estudios de Cohortes , Femenino , Hospitalización , Humanos , IncidenciaRESUMEN
OBJECTIVES: Our previous study showed that the effectiveness of tumor necrosis factor (TNF) inhibitors was attenuated in anti-human T-cell leukemia virus type 1 (HTLV-1) antibody-positive patients with rheumatoid arthritis (RA). We aimed to evaluate the effectiveness and safety of non-TNF inhibitors in anti-HTLV-1 antibody-positive patients with RA. METHODS: We reviewed patients with RA who received abatacept or tocilizumab as the first biologic agent. We used the data of patients treated with TNF inhibitors from our previous study to compare the effectiveness between the anti-HTLV-1 antibody-positive patients treated with TNF inhibitors and non-TNF inhibitors using the inverse probability of treatment weights (IPTW) method. RESULTS: A total of 359 patients were divided into anti-HTLV-1 antibody-negative and -positive patients of 332 and 27, respectively. No statistically significant difference was observed in the change in the clinical disease activity index between the anti-HTLV-1 antibody-positive and -negative patients. The results using the IPTW method showed a significant association between the non-TNF inhibitors treatment and a better response. None of the patients developed adult T-cell leukemia/lymphoma or HTLV-1-associated myelopathy/tropical spastic paraparesis during the 24 weeks. CONCLUSION: Our results indicate that non-TNF inhibitors treatment is safety, and the effectiveness is not attenuated also in anti-HTLV-1 antibody-positive patients.
Asunto(s)
Artritis Reumatoide , Virus Linfotrópico T Tipo 1 Humano , Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Humanos , Leucemia-Linfoma de Células T del Adulto , Paraparesia Espástica Tropical/tratamiento farmacológico , Inhibidores del Factor de Necrosis TumoralRESUMEN
Objective: This study aimed to investigate the time-sequential changes of risk factors for adult T-cell leukemia (ATL) development in human T-cell leukemia virus type 1 (HTLV-1)-positive rheumatoid arthritis (RA) patients. Methods: HTLV-1 infection was screened using particle agglutination assay and confirmed via western blotting in 365 RA patients. Twenty-three HTLV-1-positive RA patients were included in the study cohort. Blood samples were obtained from these patients at each observation time point. The values of HTLV-1 proviral load (PVL) and serum soluble IL-2 receptor (sIL2-R), which are risk factors for ATL development, were measured using real-time PCR and enzyme immunoassay, respectively. Results: The study cohort comprised 79 person-years. The median HTLV-1 PVL and sIL2-R values of the HTLV-1-positive RA patients were 0.44 copies per 100 white blood cells (WBCs) and 406 U/mL, respectively. Three HTLV-1-positive RA patients showed a high PVL value. No remarkable changes were observed in the PVL and sIL2-R values during the observation period. However, one elderly HTLV-1-positive RA patient who had a high PVL value developed ATL during treatment with methotrexate and infliximab. Conclusion: A thorough clinical assessment of the risk factors for ATL development may be necessary in daily clinical practice for RA patients in HTLV-1-endemic areas in Japan.
Asunto(s)
Artritis Reumatoide/epidemiología , Infecciones por HTLV-I/epidemiología , Leucemia-Linfoma de Células T del Adulto/epidemiología , Adulto , Anciano , Artritis Reumatoide/complicaciones , Femenino , Infecciones por HTLV-I/complicaciones , Humanos , Japón , Masculino , Persona de Mediana EdadRESUMEN
In this article, we discussed leukocytapheresis (LCAP) for rheumatoid arthritis (RA). Recently, a simple and practical on-line continuous LACP system has been developed. It is equipped with a direct hemoperfusion column (Cellsorba®, Asahikasei Medical Co., Ltd.) packed with fine-diameter polyester fibers, which are commonly used to adsorb white blood cells to prevent a graft-versus-host reaction during blood transfusion. Clinical trials revealed that LCAP is a effective and safe therapy for patients with drug-resistant RA or RA complicated with vasculitis. Because the procedure is simple and requires no plasma substitutes and the volume needed for extracorporeal circulation is less than that for other plasmapheresis, LCAP might be accepted as an optional therapeutic modality for active RA that was refractory to conventional drug therapy including biological agents. The mechanism of the efficiency of LCAP on RA is unclear. LCAP may cause a reduction of activated T cells from affected joints, down-regulation of Pgp on helper T cells and restoration of Treg function, and that may modify the abnormal cytokine balance. These findings may explain some of the mechanisms by which the articular symptoms are improved by LCAP.
Asunto(s)
Artritis Reumatoide/terapia , Leucaféresis/métodos , Artritis Reumatoide/sangre , HumanosRESUMEN
The study aims to assess the usefulness of human T-cell leukemia virus type 1 (HTLV-1)-infected cell analysis using flow cytometry (HAS-Flow) as a monitoring method for adult T-cell leukemia (ATL) development in HTLV-1-positive patients with rheumatoid arthritis (RA) under treatment with antirheumatic therapies. A total of 13 HTLV-1-negative and 57 HTLV-1-positive RA patients participated in this study, which was used to collect clinical and laboratory data, including HAS-Flow and HTLV-1 proviral load (PVL), which were then compared between the two groups. CADM1 expression on CD4+ cells in peripheral blood (PB) was used to identify HTLV-1-infected cells. The population of CADM1+ CD4+ cells was significantly higher in HTLV-1-positive RA patients compared to HTLV-1-negative RA patients. The population of CADM1+ CD4+ cells was correlated with HTLV-1 PVL values. There were no antirheumatic therapies affecting both the expression of CADM1 on CD4+ cells and PVLs. Six HTLV-1-positive RA patients who indicated both high HTLV-1 PVL and a predominant pattern of CADM1+ CD7neg CD4+ cells in HAS-Flow can be classified as high-risk for ATL progression. HAS-Flow could be a useful method for monitoring high-risk HTLV-1-positive RA patients who are at risk of developing ATL during antirheumatic therapies.
Asunto(s)
Antirreumáticos , Artritis Reumatoide , Virus Linfotrópico T Tipo 1 Humano , Leucemia de Células T , Adulto , Humanos , Estudios Transversales , Estudios Retrospectivos , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Provirus , Molécula 1 de Adhesión CelularRESUMEN
An elderly woman with rheumatoid arthritis (RA) presented with a chief complaint of abdominal pain and diarrhoea while undergoing treatment with low-dose corticosteroids and abatacept. Endoscopic and histopathological findings revealed manifestations of ulcerative colitis (UC). An intermediate dose of corticosteroids and 5-aminosalicylic acid were administered. Abatacept was discontinued; the anti-TNF biologic, golimumab, was administered for treatment of both RA and UC. However, colitis worsened in response to this therapeutic regimen. Colonoscopy revealed severe mucosal lesions; larvae were detected in samples taken from multiple shallow mucosal ulcers. The patient was diagnosed with Strongyloides stercoralis colitis based on the results of an anti-parasite antibody test and examination of the larval DNA. Furthermore, serology revealed a positive test for antibodies against human T-cell leukaemia virus type 1 (HTLV-1). Immunosuppressive treatment was terminated; ivermectin was administered, which resulted in improvements in colitis symptoms within a few weeks. There are several published reports describing S. stercoralis colitis as a lethal mimic of UC. Corticosteroid and anti-TNF therapies have been reported as among the major risk factors associated with strongyloidiasis in patients with HTLV-1 infection. Therefore, HTLV-1 and Strongyloides infections may be considered in cases of new-onset gastrointestinal symptoms during immunosuppressive therapy, particularly in HTLV-1-endemic regions.
Asunto(s)
Artritis Reumatoide/complicaciones , Colitis Ulcerosa/inducido químicamente , Infecciones por HTLV-I/complicaciones , Inmunosupresores/efectos adversos , Strongyloides stercoralis/aislamiento & purificación , Estrongiloidiasis/complicaciones , Anciano , Animales , Antiparasitarios/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Colitis Ulcerosa/patología , Femenino , Infecciones por HTLV-I/diagnóstico , Infecciones por HTLV-I/tratamiento farmacológico , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Humanos , Ivermectina/uso terapéutico , Estrongiloidiasis/diagnóstico , Estrongiloidiasis/tratamiento farmacológico , Inhibidores del Factor de Necrosis Tumoral/uso terapéuticoRESUMEN
BACKGROUND: CD4-positive T cells are the main target of human T-cell leukemia virus type 1 (HTLV-1). Interferon-γ release assays rely on the fact that T-lymphocytes release this cytokine when exposed to tuberculosis-specific antigens and are useful in testing for latent tuberculosis infection before initiating biologic therapy, such as anti-tumor necrosis factor agents. However, the reliability of interferon-γ release assays in detecting tuberculosis infection among HTLV-1-positive patients with rheumatoid arthritis (RA) remains unclear. The present study aimed to evaluate the use of the T-SPOT.TB assay in HTLV-1-positive RA patients. METHODS: Overall, 29 HTLV-1-positive RA patients and 87 age- and sex-matched HTLV-1-negative RA patients (controls) were included from the HTLV-1 RA Miyazaki Cohort Study. Results of the T-SPOT.TB assay for latent tuberculosis infection screening were collected from medical records of patients. RESULTS: Approximately 55% of the HTLV-1-positive RA patients showed invalid T-SPOT.TB assay results (odds ratio: 108, 95% confidence interval: 13.1-890, p < 0.0001) owing to a spot count of >10 in the negative controls. HTLV-1 proviral load values were significantly higher in patients with invalid results compared with those without invalid results (p = 0.003). CONCLUSION: HTLV-1 infection affects T-SPOT.TB assay results in RA patients. Assay results in HTLV-1 endemic regions should be interpreted with caution when screening for latent tuberculosis infection before initiation of biologic therapy.
Asunto(s)
Artritis Reumatoide/inmunología , Linfocitos T CD4-Positivos/inmunología , Infecciones por HTLV-I/inmunología , Virus Linfotrópico T Tipo 1 Humano/inmunología , Ensayos de Liberación de Interferón gamma , Tuberculosis/inmunología , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/microbiología , Artritis Reumatoide/patología , Artritis Reumatoide/virología , Linfocitos T CD4-Positivos/patología , Femenino , Infecciones por HTLV-I/microbiología , Infecciones por HTLV-I/patología , Humanos , Masculino , Persona de Mediana Edad , Tuberculosis/microbiología , Tuberculosis/patología , Tuberculosis/virologíaRESUMEN
The effects of mycotoxins on mitogen-stimulated proliferation of bovine peripheral blood mononuclear cells (PBMCs) were investigated. Aflatoxin B(1) (AFB(1)), deoxynivalenol (DON) and zearalenone (ZEN) were added to cultures of PBMCs, and the proliferation responses were measured using MTT bioassays. Suppression of the proliferation of calf PBMCs by AFB(1) and DON was significantly stronger than that of cow PBMCs, whereas there were no differences in suppressive effects on PBMCs from Holstein and Japanese Black calves and cows. The suppressive effect was greatest in the order of DON, AFB(1) and ZEN, and the effects of DON and AFB(1) seemed to be dose-dependent. The results suggest that some mycotoxins directly suppress proliferation of bovine PBMCs.
Asunto(s)
Bovinos , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/efectos de los fármacos , Mitógenos/farmacología , Micotoxinas/farmacología , Animales , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a DrogaAsunto(s)
Inmunoglobulina G/análisis , Osteoartritis de la Rodilla/diagnóstico , Osteoartritis de la Rodilla/inmunología , Membrana Sinovial/inmunología , Anciano , Artralgia/etiología , Artralgia/inmunología , Artralgia/terapia , Artroplastia de Reemplazo de Rodilla , Terapia Combinada , Femenino , Humanos , Inmunoglobulina G/sangre , Osteoartritis de la Rodilla/complicaciones , Osteoartritis de la Rodilla/terapia , Células Plasmáticas/inmunología , Tomografía de Emisión de Positrones , Prednisolona/administración & dosificación , Tomografía Computarizada por Rayos X , Pérdida de PesoRESUMEN
OBJECTIVE: Knowing the risk of hospitalized infection associated with individual biological agents is an important factor in selecting the best treatment option for patients with rheumatoid arthritis (RA). This study examined the comparative risk of hospitalized infection between biological agents in a routine care setting. METHODS: We used data for all RA patients who had first begun biological therapy at rheumatology divisions of participating community hospitals in Japan between January 2009 and December 2014. New treatment episodes with etanercept, infliximab, adalimumab, abatacept, or tocilizumab were included. Patients were allowed to contribute multiple treatment episodes with different biological agents. Incidence rates (IRs) of hospitalized infection during the first year of follow-up were examined. Cox regression analysis was used to calculate hazard ratios (HRs) for overall hospitalized infection and for pulmonary hospitalized infection, adjusting for possible confounders. RESULTS: A total of 1596 new treatment episodes were identified. The incidence of overall hospitalized infection during the first year was 86 with 1239 person-years (PYs), yielding a crude IR of 6.9 per 100 PYs (95% confidence interval [CI], 5.6-8.6). After correction for confounders, no significant difference in risk of hospitalized infection was observed between treatment groups: adjusted HRs (95% CI) were 1.54 (0.78-3.04) for infliximab, 1.72 (0.88-3.34) for adalimumab, 1.11 (0.55-2.21) for abatacept, and 1.02 (0.55-1.87) for tocilizumab compared with etanercept. Patient-specific factors such as age, RA functional class, body mass index (BMI), prednisolone use, and chronic lung disease contributed more to the risk of hospitalized infection than specific biological agents. The incidence of pulmonary hospitalized infection was 50 and a crude IR of 4.0 per 100 PYs (95% CI, 3.1-5.3). After adjustment for confounders, adalimumab had a significantly higher HR for pulmonary hospitalized infection compared with tocilizumab: an adjusted HR (95% CI) was 4.43 (1.72-11.37) for adalimumab. BMI, prednisolone use, diabetes mellitus, and chronic lung disease were also significant factors associated with the risk of pulmonary hospitalized infection. CONCLUSIONS: The magnitude of the risk of overall hospitalized infection was not determined by the type of biological agents, and patient-specific risk factors had more impact on the risk of hospitalized infection. For pulmonary hospitalized infections, the use of adalimumab was significantly associated with a greater risk of this complication than tocilizumab use.
Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Factores Biológicos/uso terapéutico , Infección Hospitalaria/epidemiología , Artritis Reumatoide/mortalidad , Demografía , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Japón/epidemiología , Masculino , Persona de Mediana Edad , Infecciones del Sistema Respiratorio/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: To investigate the response to and safety of antitumor necrosis factor (anti-TNF) therapy in human T lymphotropic virus type I (HTLV-I)positive patients with rheumatoid arthritis (RA). METHODS: Therapeutic response was evaluated in 10 HTLV-Ipositive and 20 HTLV-Inegative patients with RA (sex and age matched) at 3 months after the beginning of anti-TNF therapy using the European League Against Rheumatism improvement criteria. As secondary end points, the discontinuation rate of anti-TNF therapy and its safety, especially the development of adult T cell leukemia (ATL), were evaluated over a 2-year period. RESULTS: Significantly higher baseline levels of C-reactive protein (CRP) were observed in HTLV-Ipositive patients than in HTLV-Inegative patients (P = 0.0003). The response rate to anti-TNF therapy was lower in HTLV-Ipositive patients than in HTLV-Inegative patients. The median CRP level, erythrocyte sedimentation rate, and Disease Activity Score in 28 joints at 3 months after anti-TNF treatment in HTLV-Ipositive patients were significantly higher than in HTLV-I negative patients (P = 0.003, P = 0.03, and P = 0.003, respectively). The discontinuation rate due to insufficient response was significantly higher in HTLV-Ipositive patients than in HTLV-Inegative patients (P = 0.013). During the 2-year observation period, no patients developed ATL. CONCLUSION: These data suggest that HTLV-Ipositive patients with RA had higher inflammation and greater resistance to anti-TNF treatment than HTLV-Inegative patients. Further study is necessary to determine whether HTLV-I infection should be measured when anti-TNF agents are administered to patients with RA, especially in areas were HTLV-I is endemic.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Factores Biológicos/uso terapéutico , Infecciones por HTLV-I/tratamiento farmacológico , Virus Linfotrópico T Tipo 1 Humano , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Artritis Reumatoide/sangre , Artritis Reumatoide/inmunología , Factores Biológicos/farmacología , Femenino , Infecciones por HTLV-I/sangre , Infecciones por HTLV-I/inmunología , Virus Linfotrópico T Tipo 1 Humano/metabolismo , Humanos , Infliximab , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Neonatal Japanese Black (JB) calves show a high incidence of diarrhea. The objective of this study was to analyze the immune cell populations of neonatal JB calves in detail and examine its correlation with the incidence of diarrhea immediately after birth. Understanding the immune cell populations is helpful in clinics in order to determine the condition of the immune system for prevention of diseases. Blood samples were obtained from JB calves on the day of birth. The peripheral leukocyte populations were analyzed separately for calves that had diarrhea within 2 weeks after birth (diarrhea group; n = 26) and for calves without diarrhea (control group; n = 74). The numbers of the peripheral blood CD3(+)TcR1-N12(+) and CD8(+) T cells were significantly lower in the diarrhea group compared with the control group. These findings suggest that the congenital lower peripheral γδ and CD8(+) T cells results in a high risk of diarrhea in neonatal JB calves.