Global epidemic of human T-cell lymphotrophic virus type-I (HTLV-I): an update

Infection with human T-cell lymphotrophic virus-I (HTLV-I) is now a global epidemic, affecting 10 to 20 million people. This virus has been linked to life-threatening, incurable diseases, adult T-cell leukemia/lymphoma (ATLL), and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP), as well as several chronic illnesses, such as uveitis and dermatitis. The cumulative lifetime risk of developing these incurable diseases is approximately 5% in asymptomatic patients. For operating room personnel performing surgery among patients from high-risk groups, HTLV-I and its associated diseases are presenting an increasing challenge. This report describes its transmission, seroprevalence, treatment, and public health initiatives that must be instituted to prevent the spread of this retrovirus. Coinfection with HTLV-I and human immunodeficiency virus (HIV) has been shown to accelerate the progression of acquired immune deficiency syndrome (AIDS).     

Enhanced inhibition of lymphocyte activation by Mycobacterium avium complex in human T lymphotrophic virus type I carriers

BACKGROUND: We have previously reported that disseminated pulmonary Mycobacterium avium complex (MAC) infection is more common in human T lymphotrophic virus type I (HTLV-I) carriers than in non-carriers. However, the reason for this remains unclear. It has been shown that glycopeptidelipid (GPL), one of the lipid components of the cell envelope of MAC, is able to reduce the lymphocyte blastogenic response to mitogens. The purpose of this study was to clarify whether or not the inhibitory effect of GPL differs between HTLV-I carriers and non-carriers. METHODS: Peripheral blood lymphocytes were obtained from 29 patients who had recovered from pulmonary MAC infection (10 of whom also had HTLV-I infection) and the lymphocyte counts and T cell subpopulations of the peripheral blood lymphocytes in HTLV-I carriers and non-carriers were compared. The inhibitory effect of GPL on the lymphocyte blastogenic response to phytohaemagglutinin (PHA) was tested in these 29 cases and in 15 healthy controls who had never suffered from MAC (seven of whom also had HTLV-I infection). All HTLV-I positive cases were carriers. RESULTS: There was no significant difference in the numbers or subset proportions of T cells between HTLV-I carriers and non-carriers. Lymphocyte activation by PHA was significantly inhibited by GPL in MAC positive and negative HTLV-I carriers compared with MAC negative non-carriers and MAC negative healthy controls (p<0.001). CONCLUSIONS: We suggest that MAC infection leads to strong inhibition of lymphocyte activation in HTLV-I carriers. This may account, in part, for the severity of pulmonary MAC infection in HTLV-I carriers.     

Renal transplantation in patients with human T-cell lymphotropic virus type 1

Background

Renal transplantation (RTx) in carriers of human T-cell lymphotropic virus type 1 (HTLV-1) has a risk of developing overt leukemia upon immunosuppression. Although there have been a few reports of such cases, it is unclear HTLV-1 carrier if patients on the modern immunosuppressants would develop HTLV-1-associated myelopathy or adult T-cell leukemia lymphoma.

Methods

We retrospectively reviewed the clinical outcomes of RTx in nine HTLV-1 carriers to assess a risk of developing leukemia from 2002 to 2011 using immunosuppression with a calcineurin inhibitor, mycophenolate mofetil (MMF), and steroid. The anti-CD25 monoclonal antibody basiliximab was used for induction. In two cases of ABO-incompatible RTx, the rituximab was also administered before RTx.

Results

The ratio of male to female subjects was 2 to 7 with an overall mean recipient age of 54.3 ± 8.1 years. We prescribed cyclosporine (n = 5) or tacrolimus (n = 4). There was only one graft loss due to the death caused by aspiration pneumonia with a functioning graft. No one developed overt leukemia with combined treatment with MMF, basiliximab and rituximab.

Conclusion

We concluded that RTx in HTLV-1 carriers could be performed using a modern immunosuppressive regimen, without the risk of developing leukemia.     

Primary gastric T-cell lymphoma without human T-lymphotropic virus type 1: report of a case

Although primary gastric malignant lymphoma accounts for slightly more than 10% of all lymphomas at extranodular sites, it is relatively rare clinically, representing only 1% of all malignant diseases of the stomach. In addition, most such diseases tend to be B-cell lymphoma, while T-cell lymphoma is extremely rare. We encountered a patient with primary gastric T-cell malignant lymphoma who, although demonstrating a very rare phenomenon, was negative for antihuman T-lymphotropic virus type 1 antibody. A 73-year-old man was admitted to the hospital with the chief complaint of upper abdominal pain. The primary lesion was a type 3 tumor located at the cardia to the posterior wall of the upper body of the stomach, which had invaded the tail of the pancreas and a part of the transverse colon. A total gastrectomy, pancreatosplenectomy, and partial resection of the transverse colon were performed. The surgical section contained a giant ulcerative lesion with its bank cleaved, and a histological examination revealed a diffuse, small cell (Lymphoma Study Group classification) malignant lymphoma. An immunohistochemical analysis of the surgical specimen was positive for LCA/CD45, UCLH-1/CD45RO, and Leu-4/CD3, and negative for L-26/CD20, and it was diagnosed to be primary gastric T-cell malignant lymphoma. Received: June 28, 2001 / Accepted: November 20, 2001     

Clinical investigation of pulmonary Mycobacterium avium complex infection in human T lymphotrophic virus type I carriers

BACKGROUND: Little is known about pulmonary Mycobacterium avium complex (MAC) infection in human T lymphotrophic virus type I (HTLV-I) carriers. A study was undertaken to investigate and clarify the characteristics of pulmonary MAC infection in these subjects. METHODS: Twenty nine patients with pulmonary MAC infection without any underlying pulmonary disorder were investigated. The clinical features and radiographic appearance of HTLV-I carriers and non-carriers were compared and the bronchoalveolar lavage (BAL) fluid of these 29 patients and eight normal female control subjects was analysed. RESULTS: The prevalence of the HTLV-I carrier state in patients with pulmonary MAC infection was 34.5% (10/29) compared with 16.7% (529/3169) among all patients admitted to our department between 1994 and 1998 (odds ratio (OR) 2.63, 95% confidence interval (CI) 1.21 to 5.68). The HTLV-I carriers were all women and all had clinical symptoms, but they did not show systemic dissemination. Peripheral multifocal bronchiectasis with nodular shadowing was seen frequently on the chest computed tomographic (CT) scans of HTLV-I carriers. The area of the pulmonary lesions was more extensive than in non-carriers (p<0.05). White blood cell (WBC) counts and C reactive protein (CRP) levels on admission were significantly lower in HTLV-I carriers than in non-carriers (WBC: difference (D) = 1565/microl, 95% CI -68.9 to 3198.4/microl; CRP: D = 1.8 mg/dl, 95% CI -0.35 to 3.89 mg/dl). The concentrations of neutrophil elastase (NE) and interleukin (IL)-8 in BAL fluid were significantly higher in HTLV-I carriers than in non-carriers (NE: D = 1342 microg/l, 95% CI 704 to 1980.3 microg/l; IL-8: D = 304.5 pg/ml, 95% CI 89.7 to 519. 4 pg/ml). CONCLUSIONS: Pulmonary MAC infection causes more diffuse and widespread lesions in HTLV-I carriers than in non-carriers.     

Adult T-cell leukemia development from a human T-cell leukemia virus type I carrier after a living-donor liver transplantation

Adult T-cell leukemia (ATL) develops in a human T-cell leukemia virus type I (HTLV-I) carrier. The development of malignancy during immunosuppressive treatment following organ transplantation is one of the late fatal complications. We describe the development of three cases of ATL in eight HTLV-I carriers within 164 living-donor liver transplant recipients undergoing immunosuppressive treatment. All three cases were immunosuppressed with tacrolimus. Acute-type ATL was diagnosed at 6, 9, and 25 months after living-donor liver transplantation, based on increased numbers of CD4+25+ lymphocytes exhibiting "flower-like" nuclei, and the elevation of lactate dehydrogenase. Southern blot analysis demonstrated the clonal proliferation of ATL cells in peripheral blood. The ATL cells originated from the recipient, as demonstrated by fluorescence in situ hybridization analysis using sex chromosomal markers. Our observations suggest that immunosuppressive treatment for the prevention of graft rejection after living-donor liver transplantation may induce the development of ATL in an HTLV-I carrier.     

Half-joint allograft transplantation in human bone tumours

Summary Seven patients with malignant or aggressive bone tumours involving the end of a long bone have been treated by wide resection and an allograft providing a half-joint transplantation. The observation period is from 2 to 9 years (average 5 years). The allografts were preserved at –70 °C for a period ranging from 1 week to more than 2 years. Computed tomography was very useful in the preoperative determination of the grade of infiltration tumour growth in bone. The host's own ligaments were used in the reconstruction. Immunosuppression was not used.The fate and metabolism of the allografts were followed by clinical examination, conventional radiographs, angiography, bone scintigraphy, cell-mediated immunity tests, biopsies for histology and by determining the excretion of the urinary products of bone metabolism (duHYPro, dUCa, dUPi). Positive isotope labelling was demonstrated as early as 2 weeks after transplantation and this increased and stabilised at about 6 months. Simultaneously, the collagen/bone matrix turnover (HYPro excretion) showed a slightly raised level for up to 3–6 months, stabilising thereafter indicating a moderate, but prolonged, regenerative activity of the graft. On the basis of these and the histological studies, weight-bearing was gradually started at 6 months, which is earlier than described in previous reports. The patients had knee flexion up to 90° and walked well. Studies on whole-blood cell-mediated immunity showed only slight non-significant changes. The results indicate that the grafts incorporated well with early, and subsequently prolonged, evidence of metabolic activity.

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Résumé 7 malades atteints de tumeurs osseuses malignes ou aggressives situées au niveau de l'extrémité d'un os long ont été traités par résection large et allogreffe, réalisant la transplantation d'une hémi-articulation. La durée d'observation est de 2 à 9 ans (en moyenne 5 ans). Les allogreffes ont été conservées à –70° pendant une période allant d'une semaine à plus de 2 ans. La tomographie computerisée a été très utile pour la détermination pré-opératoire du degré d'infiltration de la croissance tumorale osseuse. Les ligaments du sujet receveur ont été utilisés pour la reconstruction. On n'a pas eu recours à l'immuno-suppression.L'évolution et le métabolisme des allogreffes ont été suivis grâce à l'examen clinique, aux radiographies standard, à l'angiographie, à la scintigraphie osseuse, aux tests d'immunité cellulaire, aux biopsies pour examen histologique et en déterminant l'excrétion urinaire des produits du métabolisme osseux (hydroxyproline) calcium et phosphates). Des réactions isotopiques positives se sont manifestées dès la deuxième semaine après la transplantation, puis ont augmenté et se sont stabilisées vers le 6ème mois. Simultanément, le »turnover« collagène/matrice osseuse (excrétion de l'hydroxyproline) a montré une légère augmentation pendant 3 à 6 mois, indiquant une activité de régénération de la greffe, modérée mais prolongée. Du fait de ces constatations et des résultats des examens histologiques, la reprise de l'appui a été progressivement autorisée à partir du 6ème mois, c'est à dire plus tôt qu'il n'est dit dans les publications plus anciennes. Les malades ont récupéré une flexion du genou atteignant 90° et marchent correctement. L'étude de l'immunité cellulaire sanguine n'a montré que de minimes changements, non significatifs. Ces résultats prouvent que les greffes s'incorporent bien, avec des signes d'activité métabolique précoce et longtemps prolongée.

     

Human immunodeficiency virus and human T-cell leukemia virus type I in patients undergoing maintenance hemodialysis in Miami

The high prevalence of human immunodeficiency virus (HIV-1) infection in populations at risk in Miami prompted a seroepidemiologic study of both HIV-1 and the human T-cell leukemia virus type I (HTLV-I), a closely related virus, in our patients receiving chronic hemodialysis. One hundred twenty-nine patients undergoing hemodialysis in 1986 and 1987 were tested for antibody against both viral antigens by EIA (Abbott Laboratories, Abbott Park, IL). Seroreactive samples for HIV-1 and/or HTLV-I were confirmed by Western blot and, for HTLV-I, by viral cultures. Thirty patients (23.2%) were positive for retroviral infection (22 for HIV-1 alone, four for HTLV-I alone, and four for both HIV-1 and HTLV-I). The most important risk factor was intravenous drug use, followed by blood transfusion. Patients with HIV-1 had lower T4-T8 ratios and higher mortality than those with HTLV-I infection alone. It was concluded that HTLV-I, as well as HIV-1, infection is endemic in chronic dialysis centers in Miami. The clinical consequences of HTLV-I infection in relatively immunocompromised patients with chronic uremia who are undergoing chronic hemodialysis remains to be established.     

Helper T-cell type 1 or type 2 function of xeno-MHC-restricted T-cell clones in a direct xenoantigen recognition

There have been several reports that xeno-MHC-restricted T-cells have a cytotoxic function through a direct xenoantigen recognition, but yet no report that they have a helper function. Previously we showed that both xeno-MHC-restricted CD4(+) and CD8(+) T-cells recognized xenoantigens directly in a mouse anti-rat combination. In this study, we investigated whether or not xeno-MHC-restricted T-cells had a helper function. Mouse T-cell clones recognizing rat antigens directly were derived from T-cell lines using the limiting dilution method. Phenotype, cytotoxic activity and cytokine production of these clones were analyzed by flow cytometry, 51Cr release assay and ELISA, respectively. Rat-MHC class I-restricted mouse CD8(+) T-cell clones showed a specific cytotoxic activity against rat antigens. One CD4(+) clone produced IL-4 and IL-10, and the other CD4(+) clone produced not T-helper (Th) 2 cytokine but TNF-alpha. Our results suggested that xeno-MHC class I-restricted CD8(+) T-cells should have a cytotoxic function, and xeno-MHC class II-restricted CD4(+) T-cells should have either Th1 or Th2 function.     

IgA nephropathy in a child with human immunodeficiency virus type 1 infection

Infection with the human immunodeficiency virus type 1 (HIV-1) can cause a spectrum of renal disease, termed acquired immunodeficiency syndrome (AIDS) nephropathy. The most common clinical manifestations of kidney involvement in HIV-1-infected patients are proteinuria and/or nephrotic syndrome, and the histopathological pattern usually reveals focal segmental glomerulosclerosis. We describe an 8-year-old child with AIDS who presented with recurrent gross hematuria. A kidney biopsy demonstrated IgA nephropathy. This unique case indicates that the range of kidney disease in HIV-infected children may be broader than originally thought, and that these patients warrant a complete evaluation of any renal abnormality.     

Current procedures for banking allograft human bone.

The demand for bone and soft tissues for surgical usage has increased rapidly as the efficacy and safety of these materials has been demonstrated. Advances in technology and procedures used to prepare the tissues have also grown in sophistication and remain a dynamic area. How tissue banks screen donors and prepare allografts impacts on the risks and benefits of these materials. Surgeons should understand how tissue banks supplying their graft materials work and have confidence in this treatment option. They will then be prepared to educate their patients to help them make informed decisions concerning allograft usage.     

CD8+ T-cell responses identify beta-cell autoimmunity in human type 1 diabetes

Despite the understanding that type 1 diabetes pathogenesis is mediated by T-cells, detection of these rare lymphocytes remains largely elusive. Suitable T-cell assays are highly needed, since they could offer preclinical diagnoses and immune surrogate end points for clinical trials. Although CD4+ T-cell assays have met with limited success, CD8+ T-cells are increasingly recognized as key actors in the diabetes of the NOD mouse. CD8+ T-cells are likely to play a role also in humans and may provide new markers of beta-cell autoimmunity. Taking advantage of a panel of HLA-A2-restricted beta-cell epitopes derived from preproinsulin, GAD, and islet glucose-6-phosphatase catalytic subunit-related protein (IGRP), we have implemented an islet-specific CD8+ T-cell interferon-gamma enzyme-linked immunospot (ISL8Spot) assay. The ISL8Spot assay is capable of detecting and quantifying beta-cell-reactive CD8+ T-cells directly ex vivo, without any preliminary expansion, using either fresh or frozen samples. Positive ISL8Spot responses separate new-onset diabetic and healthy samples with high accuracy (86% sensitivity, 91% specificity), using as few as five immunodominant epitopes. Moreover, sensitivity reaches 100% when the ISL8Spot assay is complemented by antibody determinations. Combination of CD8+ T-cell measurements with immune intervention strategies may open new avenues toward type 1 diabetes prediction and prevention.     

Depression of evoked electromyographic (EEMG) responses by propofol in a patient with human T-cell lymphotropic virus type I-associated myelopathy (HAM)

IMPLICATIONS: We report a patient with human T-cell lymphotropic virus type I-associated myelopathy. Although muscle strength in both of the upper extremities was normal in this patient, evoked electromyogram of the adductor pollicis was depressed by propofol at the induction of anesthesia.     

Distribution and possible spread of human T-cell leukaemia virus type I in human communities in the northern and eastern Transvaal

The prevalence of serum antibodies which probably indicate infection with a human T-cell leukaemia virus type I was determined among random population samples of more than 100 healthy black individuals in several localities in Transvaal. The percentage of seropositive subjects increases northwards and eastwards, where geoclimatic conditions are similar to those of endemic areas elsewhere in the world. The comparatively higher prevalence among females in the Kruger National Park suggests that this is predominantly a sexually transmitted disease.     

Lymphoma of the maxillary sinus in a patient infected with human immunodeficiency virus type 1

A 27-year-old woman with a history of intravenous drug abuse presented with a stage IE, diffuse, large cell lymphoma of the right maxillary sinus. A test for antibodies to the human immunodeficiency virus was positive. The patient was treated with systemic chemotherapy and local maxillary sinus irradiation which resulted in complete regression of the disease. Therapy was complicated by mucositis, neutropenia, and opportunistic infections. This is the first case report to discuss the presentation and treatment of acquired immunodeficiency syndrome (AIDS)-related lymphoma of the maxillary sinus.