Trends in HTLV‐1 prevalence and incidence of adult T‐cell leukemia/lymphoma in Nagasaki,Japan

Most previous studies aimed at estimating the number of human T‐cell leukemia virus type‐1 (HTLV‐1) carriers in endemic areas have been based on seroprevalence rates in blood donors; however, this may result in underestimation because of the healthy donor effect. People who have health problem do not donate blood. In the present study, the number of HTLV‐1 carriers in Nagasaki City was estimated based on the seroprevalence rates in a hospital‐based population from Nagasaki University Hospital. In accordance with previous reports, seroprevalence of HTLV‐1 was higher in females, and year of birth‐specific seroprevalence showed a significant annual decline in both genders (P for trend: <0.0001). The estimated number of HTLV‐1 carriers in Nagasaki City was 36,983. The incidence of adult T‐cell leukemia/lymphoma (ATLL) among HTLV‐1 carriers was estimated using data from the Nagasaki Prefectural Cancer Registry. The estimated annual incidence of ATLL was 61 per 100,000 HTLV‐1 carriers, and the crude lifetime risk of the development was 7.29% for males and 3.78% for females. There is a large pool of HTLV‐1 carriers aged over 70 years, and a continuing development of cases of ATLL among the elderly is therefore expected. J. Med. Virol. 82:668–674, 2010. © 2010 Wiley‐Liss, Inc.     

Cytological diagnosis of adult T‐cell leukemia/lymphoma in sputum

Adult T‐cell leukemia/lymphoma (ATLL) is a rare and often aggressive T‐cell leukemia/lymphoma that has been linked to infection by the human T‐cell lymphotropic virus type 1 (HTLV‐1). ATLL can involve multiple organs including the respiratory airway. A 53‐year‐old Trinidadian woman presented with productive cough and progressive shortness of breath. Her past medical history included duodenal strongyloidosis, skin rash, and hypercalcemia. Radiological studies showed increased interstitial markings. Sputum cytology showed atypical pleomorphic, small‐to‐medium‐sized, lobated lymphocytes with irregular and hyperchromatic nuclei resembling “flower cells” which were CD3±/CD20? by immunocytochemistry. A lung biopsy showed interstitial, peribronchiolar, and subpleural infiltration by a CD3±/CD25± atypical lymphocytic infiltrate. Together with peripheral blood findings and positive HTLV‐1 serology, the diagnosis of ATLL was made. We suggest that sputum evaluation in patients with ATLL risk factors can be diagnostic. Diagn. Cytopathol. 2016;44:416–418. © 2016 Wiley Periodicals, Inc.     

Quantitative PCR for HTLV‐1 provirus in adult T‐cell leukemia/lymphoma using paraffin tumor sections

Detection of HTLV‐1 provirus using paraffin tumor sections may assist the diagnosis of adult T‐cell leukemia/lymphoma (ATLL). For the detection, non‐quantitative PCR assay has been reported, but its usefulness and limitations remain unclear. To our knowledge, quantitative PCR assay using paraffin tumor sections has not been reported. Using paraffin sections from ATLLs and non‐ATLL T‐cell lymphomas, we first performed non‐quantitative PCR for HTLV‐1 provirus. Next, we determined tumor ratios and carried out quantitative PCR to obtain provirus copy numbers. The results were analyzed with a simple regression model and a novel criterion, cut‐off using 95 % rejection limits. Our quantitative PCR assay showed an excellent association between tumor ratios and the copy numbers (r = 0.89, P < 0.0001). The 95 % rejection limits provided a statistical basis for the range for the determination of HTLV‐1 involvement. Its application suggested that results of non‐quantitative PCR assay should be interpreted very carefully and that our quantitative PCR assay is useful to estimate the status of HTLV‐1 involvement in the tumor cases. In conclusion, our quantitative PCR assay using paraffin tumor sections may be useful for the screening of ATLL cases, especially in HTLV‐1 non‐endemic areas where easy access to serological testing for HTLV‐1 infection is limited.     

CD4 and CD8 double‐negative adult T‐cell leukemia/lymphoma with monomorphic cells expressing CD99: A diagnostic challenge in a country non‐endemic for human T‐cell leukemia virus

Adult T‐cell leukemia/lymphoma (ATLL) is a peripheral T‐cell neoplasm caused by human T‐cell lymphotropic virus type I (HTLV‐I). The neoplastic cells are highly pleomorphic and are usually CD4+ and CD8? phenotypically. We reported the case of a 46‐year‐old woman presenting with fever, abdominal distention, lymphadenopathy, leukocytosis and hypercalcemia. Nodal biopsy showed diffuse infiltration by monomorphic small to medium‐sized atypical lymphocytes expressing CD3, CD25, CD30 and CD99, but not CD1a, CD4, CD8, CD34, terminal deoxynucleotidyl transferase or ALK. An initial diagnosis of T‐lymphoblastic leukemia/lymphoma was made based on cytomorphology, CD4 and CD8 double negativity, and the expression of CD99. The diagnosis was later revised to ATLL based on the positive serology study for anti‐HTLV I/II antibody and confirmation by the clonal integration of HTLV‐I proviral DNA into the tumor tissues by Southern blotting analysis. The patient had a stage IVB disease and died of septic shock after 2 courses of chemotherapy 3 months after diagnosis. Immunohistochemical staining for CD99 in archival ATLL tissues showed a positive rate of 67% (4 of 6 tumors). Our case showed that ATLL with atypical morphology and immunophenotype in HTLV non‐endemic areas might pose a diagnostic challenge and CD99 expression is frequent in ATLL.     

Infective dermatitis has similar immunological features to human T lymphotropic virus‐type 1‐associated myelopathy/tropical spastic paraparesis

Human T lymphotropic virus‐type 1 (HTLV‐1) is the causal agent of the HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP), adult T cell leukaemia/lymphoma and infective dermatitis associated with HTLV‐1 (IDH). Over‐production of proinflammatory cytokines and an increase in HTLV‐1 proviral load are features of HAM/TSP, but the immunological basis of IDH has not been established. In addition to severe cutaneous manifestations, the importance of IDH relies on the observation that up to 30% of children with IDH develop HAM/TSP in childhood and adolescence. In this study we determined the immune response in patients with IDH measuring interleukin (IL)‐4, IL‐5, IL‐10, interferon (IFN)‐γ and tumour necrosis factor (TNF)‐α levels as well as the HTLV‐1 proviral load. Additionally, regulatory cytokines and anti‐cytokines were added to cultures to evaluate the ability of these molecules to down‐modulate TNF‐α and IFN‐γ synthesis. HTLV‐1 carriers and patients with HAM/TSP served as controls. TNF‐α and IFN‐γ levels were higher in IDH than in HTLV‐1 carriers. There was no difference in IFN‐γ and TNF‐α concentrations in IDH and HAM/TSP patients. There was a tendency for higher IL‐4 mRNA expression and immunoglobulin E (IgE) levels in IDH than in HTLV‐1 carriers, but the difference did not reach statistical significance. The HTLV‐1 proviral load was significantly higher in IDH patients than in HTLV‐1 carriers. IDH is characterized by an exaggerated Th1 immune response and high HTLV‐1 proviral load. The similarities between the immunological response in patients with IDH and HAM/TSP and the high proviral load observed in IDH provide support that IDH is a risk factor for development of HAM/TSP.     

T‐cell prolymphocytic leukemia (T‐PLL) with overlapping cytomorphological features with T‐CLL and T‐ALL: A Case Initially Diagnosed by Fine‐Needle Aspiration Cytology and Immunocytochemistry

T‐cell prolymphocytic leukemia (T‐PLL) is a very unusual form of chronic lymphoproliferative disorder, which has rarely been diagnosed by fine needle aspiration (FNA) cytology. We report one such case with some overlapping cytomorphological features with chronic lymphocytic leukemia and acute lymphoblastic leukemia. A 91‐year‐old man presented with generalized lymphadenopathy, pleural effusion, ascites, and an ulcerated growth in rectum. FNA smears from the left cervical lymph node showed a monotonous population of small lymphoid cells having small but distinct nucleoli that was initially diagnosed as chronic lymphocytic leukemia (CLL). Smears from the left axillary lymph node contained both small and medium‐sized lymphoid cells with frequent hand‐mirror cell appearance, which has been described in acute lymphoblatic leukemia (ALL). Immunocyto/histochemical stainings on smears and cell block preparations of the aspirate showed the following immunophenotype: CD3+, CD4+, CD5+, CD7+, CD8‐, CD20‐, CD23‐, and Tdt‐. Total peripheral blood leukocyte count was 26.4 × 10⁹/L and total lymphocyte count, 8.3 × 10⁹/L with predominance of small lymphocytes. T‐cell nature of the neoplasm was confirmed by biopsies from the cervical lymph node (T‐cell lymphoma), bone marrow (T‐cell lymphoid neoplasm/chronic lymphocytic leukemia), and the ulcerated rectal lesion (atypical T‐cell lymphoproliferative disorder). The patient developed deep vein thrombosis, heparin‐induced thrombocytopenia and bleeding from duodenal ulcer. By the time the reports of all the investigations were ready, the patient succumbed to bronchopneumonia. To the best of our knowledge, this T‐CLL/T‐PLL which was diagnosed initially by FNA cytology with immunocytochemical support is first of its kind to be reported. Diagn. Cytopathol. 2013;41:360–365. © 2011 Wiley Periodicals, Inc.     

Polymorphisms at GLUT1 gene are not associated with the development of TSP/HAM in Brazilian HTLV‐1 infected individuals and the discovery of a new polymorphism at GLUT1 gene

The development of HTLV‐1 associated clinical manifestations, such as TSP/HAM and ATLL, occur in 2–4% of the infected population and it is still unclear why this infection remains asymptomatic in most infected carriers. Recently, it has been demonstrated that HTLV uses the Glucose transporter type 1 (GLUT1) to infect T‐CD4⁺ lymphocytes and that single nucleotide polymorphisms (SNP) in the GLUT1 gene are associated with diabetic nephropathy in patients with diabetes mellitus in different populations. These polymorphisms could contribute to a higher GLUT1 protein expression on cellular membrane, facilitating the entry of HTLV and its transmission cell by cell. This could result in a higher provirus load and consequently in the development of TSP/HAM. To evaluate the role of GLUT1 gene polymorphisms in the development of TSP/HAM in HTLV‐1 infected individuals, the g.22999G > T, g.15339T > C and c.‐2841A > T sites were analyzed by PCR/RFLP or sequencing in 244 infected individuals and 102 normal controls. The proviral load of the HTLV‐1 infected patients was also analyzed using Real Time Quantitative PCR. Genotypic and allelic frequencies of the three sites did not differ significantly between controls and HTLV‐1 infected individuals. There was no difference in genotypic and allelic distributions among patients as to the presence or absence of HTLV‐1 associated clinic manifestations. As regards the quantification of the provirus load, we observed a significant reduction in the asymptomatic individuals compared with the oligosymptomatic and TSP/HAM individuals. These results suggest that g.22999G > T, g.15339T > C, and c.‐2841A > T SNP do not contribute to HTLV‐1 infection nor to the genetic susceptibility of TSP/HAM in Brazilian HTLV‐1 infected individuals. J. Med. Virol. 81:552–557, 2009. © 2009 Wiley‐Liss, Inc.     

Immunological and viral features in patients with overactive bladder associated with human T‐cell lymphotropic virus type 1 infection

The majority of patients infected with human T‐cell lymphotropic virus‐type 1 (HTLV‐1) are considered carriers, but a high frequency of urinary symptoms of overactive bladder, common in HTLV‐1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) have been documented in these patients. The aim of this study was to determine if immunological and viral factors that are seen in HAM/TSP are also observed in these patients. Participants were classified as HTLV‐1 carriers (n = 45), HTLV‐1 patients suffering from overactive bladder (n = 45) and HAM/TSP (n = 45). Cells from HTLV‐1 overactive bladder patients produced spontaneously more proinflammatory cytokines than carriers. TNF‐α and IL‐17 levels were similar in HAM/TSP and HTLV‐1 overactive bladder patients. High proviral load was found in patients with overactive bladder and HAM/TSP and correlated with proinflammatory cytokines. In contrast with findings in patients with HAM/TSP, serum levels of Th1 chemokines were similar in HTLV‐1 overactive bladder and carriers. Exogenous addition of regulatory cytokines decreased spontaneous IFN‐γ production in cell cultures from HTLV‐1 overactive bladder patients. The results show that HTLV‐1 overactive bladder and HAM/TSP patients have in common some immunological features as well as similar proviral load profile. The data show that HTLV‐1 overactive bladder patients are still able to down regulate their inflammatory immune response. In addition, these patients express levels of chemokines similar to carriers, which may explain why they have yet to develop the same degree of spinal cord damage as seen in patients with HAM/TSP. These patients present symptoms of overactive bladder, which may be an early sign of HAM/TSP. J. Med. Virol. 84:1809–1817, 2012. © 2012 Wiley Periodicals, Inc.     

Virological and immunological mechanisms in the pathogenesis of human T‐cell leukemia virus type 1

Human T‐cell leukemia virus type 1 (HTLV‐1) was the first retrovirus shown to cause human disease, such as adult T‐cell leukemia and HTLV‐1 associated myelopathy/tropic spastic paraparesis. HTLV‐1 mainly infects CD4 T cells and deregulates their differentiation, function and homeostasis, which should contribute to the pathogenesis of HTLV‐1, for example, inducing transformation of infected CD4 T cells and chronic inflammatory diseases. Therefore, not only virological approach but also immunological approach regarding CD4 T cells are required to understand how HTLV‐1 causes related human diseases. This review focuses on recent advances in our understanding of the interaction between HTLV‐1 and the main host cell, CD4 T cells, which should provide us some clue to the mechanisms of HTLV‐1 mediated pathogenesis. Copyright © 2013 John Wiley & Sons, Ltd.     

Fine‐scale geographic clustering pattern of human T‐cell leukemia virus type 1 infection among blood donors in Kyushu‐Okinawa,Japan

Human T‐cell leukemia virus type I (HTLV‐1) infection is endemic in Japan, particularly clustered in the southwestern district, Kyushu‐Okinawa, which consists of eight prefectures that further consist of 274 municipalities. However, no information is available about the fine‐scale distribution of HTLV‐1 infection within Kyushu‐Okinawa. To assess the municipal‐level distribution of people with HTLV‐1 infection in Kyushu‐Okinawa, we performed a cross‐sectional study using a fine‐scale geographic information system map based on HTLV‐1 screening test results from the Japanese Red Cross database from September 2012 to February 2014. Of the 881 871 (646 914 male, 234 957 female) screened blood donors, 981 were seropositive for HTLV‐1 by confirmatory test. The seroprevalence was 0.11% (95% confidence interval [CI] 0.10%‐0.12%) for all, 0.094% (95% CI, 0.09%‐0.10%) for male, and 0.16% (95% CI, 0.14%‐0.18%) for female individuals. The sex‐ and age‐specific HTLV‐1 seroprevalence varied significantly across municipalities; particularly, the seroprevalence among women aged 50 years was significantly higher than that of men in both the mainland of Kyushu‐Okinawa and the satellite island, in all of which the seroprevalence of HTLV‐1 was more than 1.2%. These results show that, even in the Kyushu‐Okinawa district, there are endemic clusters of HTLV‐1 in small areas. This suggests that public health education programs are needed to eliminate new HTLV‐1 infection in these areas.     

Non‐specific interstitial pneumonia as a manifestation of graft‐versus‐host disease following pediatric allogeneic hematopoietic stem cell transplantation

Bronchiolitis obliterans (BO) is generally believed to be a marker of pulmonary manifestation of graft‐versus‐host disease (GVHD) in patients who have undergone bone marrow transplantation for hematological malignancy. Pulmonary manifestations reported as GVHD (other than BO) include lymphocytic bronchiolitis with cellular interstitial pneumonia, lymphoid interstitial pneumonia, veno‐occlusive disease, and diffuse alveolar damage. Morphological reactions in the lungs of bone marrow transplant recipients associated with interstitial pneumonia have not been described systematically. Reported herein is a fibrosing non‐specific interstitial pneumonia (NSIP) pattern together with BO in both lungs in an 8‐year‐old girl following a second allogeneic hematopoietic stem cell transplantation for relapsed neuroblastoma of adrenal origin. The course was complicated by bilateral pneumothoraces, and the patient underwent lung transplantation 3 years after the second stem cell transplantation. Because the patient had chronic GVHD of the skin and the liver preceeded by the development of pulmonary involvement, NSIP may represent one of the facets of pulmonary GVHD.     

Correlation of HTLV‐1 Tax genetic diversity with HTLV‐1 associated myelopathy/tropical spastic paraparesis progression and HTLV‐1a genotypes in an HTLV‐1 endemic region in Argentina

The oncoprotein Tax was characterized genetically from a large cohort of human T‐cell lymphotropic virus type 1 (HTLV‐1) seropositive individuals from the most endemic region of HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV‐1 infection in Argentina, the province of San Salvador de Jujuy. Sixteen HAM/TSP patients and 47 HTLV‐1 healthy carriers were evaluated. Six Tax genetic polymorphisms were identified and observed in 70.8% of healthy carriers and 62.5% of HAM/TSP patients. Tax genetic polymorphisms were not associated with clinical status but A8344C polymorphism statistically provide a borderline protective effect of HAM/TSP outcome. Nucleotide diversity in healthy carriers was 0.00549, whereas HAM/TSP virus population revealed a low diversity of 0.00379, suggests a positive selection for Tax protein conservation in this group. It is concluded that tax genetic polymorphisms do not increase the risk of developing HAM/TSP in this endemic region. However, in spite of the low prevalence of HTLV‐1aB genotype, statistical analysis revealed an important correlation of tax genetic signatures with HTLV‐1aA trans‐continental subgroup. J. Med. Virol. 82:1438–1441, 2010. © 2010 Wiley‐Liss, Inc.     

Lower numbers of circulating natural killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV‐1) associated neurological disease

Human T lymphotropic virus type 1 (HTLV‐1) infects 10–20 million people worldwide. The majority of infected individuals are asymptomatic; however, approximately 3% develop the debilitating neurological disease HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is also currently no cure, vaccine or effective therapy for HTLV‐1 infection, and the mechanisms for progression to HAM/TSP remain unclear. NK T cells are an immunoregulatory T cell subset whose frequencies and effector functions are associated critically with immunity against infectious diseases. We hypothesized that NK T cells are associated with HAM/TSP progression. We measured NK T cell frequencies and absolute numbers in individuals with HAM/TSP infection from two cohorts on two continents: São Paulo, Brazil and San Francisco, CA, USA, and found significantly lower levels when compared with healthy subjects and/or asymptomatic carriers. Also, the circulating NK T cell compartment in HAM/TSP subjects is comprised of significantly more CD4⁺ and fewer CD8⁺ cells than healthy controls. These findings suggest that lower numbers of circulating NK T cells and enrichment of the CD4⁺ NK T subset are associated with HTLV‐1 disease progression.     

Oral health profile in patients infected with HTLV-1: clinical findings, proviral load, and molecular analysis from HTLV-1 in saliva

Human T‐lymphotropic virus type 1 (HTLV‐1) is associated with adult T‐cell leukemia (ATL) and HTLV‐1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and has also been implicated in several disorders, including periodontal disease. The proviral load is an important biological marker for understanding HTLV‐1 pathogenesis and elucidating whether or not the virus is related to the clinical manifestation of the disease. This study describes the oral health profile of HTLV‐1 carriers and HAM/TSP patients in order to investigate the association between the proviral load in saliva and the severity of the periodontal disease and to examine virus intra‐host variations from peripheral blood mononuclear cells and saliva cells. It is a cross‐sectional analytical study of 90 individuals carried out from November 2006 to May 2008. Of the patients, 60 were HTLV‐1 positive and 30 were negative. Individuals from the HTLV‐1 positive and negative groups had similar mean age and social‐economic status. Data were analyzed using two available statistical software packages, STATA 8.0 and SPSS 11.0 to conduct frequency analysis. Differences of P < 0.05 were considered statistically significant. HTLV‐1 patients had poorer oral health status when compared to seronegative individuals. A weak positive correlation between blood and saliva proviral loads was observed. The mean values of proviral load in blood and saliva in patients with HAM/TSP was greater than those in HTLV‐1 carriers. The HTLV‐1 molecular analysis from PBMC and saliva specimens suggests that HTLV‐1 in saliva is due to lymphocyte infiltration from peripheral blood. A direct relationship between the proviral load in saliva and oral manifestations was observed. J. Med. Virol. 84:1428–1436, 2012. © 2012 Wiley Periodicals, Inc.     

HTLV‐1 and ‐2 in a first‐time blood donor population in Northeastern Brazil: Prevalence,molecular characterization,and evidence of intrafamilial transmission

Independent epidemiology for respective human T‐cell lymphotropic virus (HTLV) types 1 and 2 is little known in blood donors in Brazil, where screening for HTLV‐1/2 is mandatory at blood banks, but no testing to confirm/differentiate these viruses. Therefore, this study aims to assess the prevalence of HTLV‐1 and ‐2 in a first‐time blood donor population in Northeastern Brazil and to carry out molecular characterization of respective isolates. A cross‐sectional study was conducted at the State Blood Bank in Piauí. Samples were screened for anti–HTLV‐1/2 by enzyme immunoassay, and reactive samples were confirmed using a line immunoassay and polymerase chain reaction (PCR). Of 37 306 blood donors, 47 were anti–HTLV‐1/2 reactive by enzyme immunoassay. After confirmed by line immunoassay, 22 were positive for HTLV‐1 (0.59 per 1000; 95% CI: 0.38‐0.87), 14 were positive for HTLV‐2 (0.37 per 1000; 95% CI: 0.21‐0.61), 1 was indeterminate, and the remaining donors were negative. The HTLV‐1 infection was also confirmed by PCR in all anti–HTLV‐1‐positive samples, and sequencing classified these isolates as belonging to the Transcontinental (A) subgroup of the Cosmopolitan (1a) subtype. Of 14 anti–HTLV‐2‐positive samples, 11 were also PCR positive, which belonged to subtype a (HTLV‐2a/c). In addition, 38 family members of 5 HTLV‐1‐ and 3 HTLV‐2‐infected donors were analyzed. Familial transmission of HTLV‐1 and ‐2 was evidenced in 3 families. In conclusion, in Northeastern Brazil, where HTLV‐1 and ‐2 are endemic, counseling blood donor candidates and their families might play a key role in limiting the spread of these viruses.     

Frequent expression of gp46 in adult T-cell leukemia/lymphoma: an immunohistochemical study of 40 cases

Adult T-cell leukemia/lymphoma (ATLL) is a lymphoproliferative disease caused by human T-cell lymphotropic virus type 1 (HTLV-1) infection. HTLV-1 is spread by cell-to-cell transmission via the gp46-197 region, from Asp197 to Leu216, in the envelope protein gp46. A correlation exists between the prevalence and titer of the antibody recognizing the gp46-197 region (anti-gp46-197 antibody) and the severity of ATLL. In the present study, immunohistochemical staining was performed on samples of paraffin embedded lymph nodes of three different histological types of ATLL (anaplastic large cell type, n = 10; pleomorphic type, n = 10; and Hodgkin's-like type, n = 10) from 30 cases and 10 cases of HTLV-associated lymphadenitis. Of the three ATLL subtypes, gp46 expression was highest in the anaplastic large cell type, followed by the pleomorphic type and Hodgkin's-like type (mean: 53.4%, 34.9% and 16.0%, respectively; P= 0.0003). In HTLV-1 associated lymphadenitis cases, gp46 positive cells were rarely seen (4.0%). These results suggest that gp46-197 immunohistochemical staining can be a useful histological indicator for prediction of the aggressiveness of ATLL and prognosis for ATLL patients.     

Evaluation of a new screening assay for HTLV‐1 and ‐2 antibodies for large‐scale use

Laboratory testing for Human T‐lymphotropic Virus type 1 and 2 (HTLV‐1 and ‐2) infections has become routine in blood transfusion, tissue transplantation and clinical diagnoses in many countries worldwide. Screening is usually based on the detection of antibodies to HTLV‐1 and/ or ‐2. The number of commercially available assays is limited, and among them, ELISA tests based on microtiter format are most commonly used. Recently, the new rHTLV‐I/II assay (Abbott Laboratories, Abbott Park, IL) was released; this assay was developed for an automatic large‐scale screening platform. This assay was evaluated using pre‐characterized serum panels and routine samples from the clinical laboratory. The sensitivity was 100% for HTLV‐1 and ‐2 (99/99 and 42/42, respectively, including one sample that was dually reactive, HTLV‐1 + 2). To test assay specificity, panels of blood donor sera, specimens from patients with autoimmune diseases and some viral infections were used. False‐reactive samples from previous HTLV diagnoses were also included. With these panels, the specificity was 99.4% (619/623). However, the four false‐reactive samples all belonged to the group of samples that were previously considered as false‐reactive for HTLV‐antibodies. All other samples were negative by the rHTLV‐I/II assay, and thus 100% specificity was obtained. The 1,412 samples tested in the clinic by this assay in routine use were all negative (100% specificity). Taken together, the overall specificity was 99.8%. The assay was sensitive, specific and appropriate for the large‐scale screening of samples for HTLV‐1/2 antibodies. J. Med. Virol. 82:1606–1611, 2010. © 2010 Wiley‐Liss, Inc.     

Lymphoid interstitial pneumonia: clinicopathological and immunopathological findings in 18 cases

Eighteen patients with lymphoid interstitial pneumonia (LIP) were studied. The diagnosis was established by the microscopic finding of interstitial infiltrates of lymphocytes and plasma cells. Forty-seven% of patients also had germinal centres, while 72% showed interstitial giant cells. Cases studied by the immunoperoxidase technique showed the interstitial plasma cells to be polytypic. The median age of patients was 56 years; most had cough, dyspnea, or chest pain. Chest X-rays showed either patchy interstitial infiltrates (usually bilateral) or poorly defined nodules. Ten patients had hypergammaglobulinemia; one had hypogammaglobulinemia. Two patients had Sj?gren's syndrome, two had biopsy-proven chronic active hepatitis, and two had a clinical diagnosis of primary biliary cirrhosis. Follow-up examination of 14 patients showed clearing of symptoms, X-ray infiltrates or stable infiltrates in 4 cases each. Five patients died (mean survival, 41 months), one of whom succumbed to disseminated lymphoma and a second to respiratory failure. Our results support the hypothesis that LIP is a non-neoplastic cellular proliferation in which lymphoma may supervene. The high incidence (22%) of chronic liver disease has not previously been noted.