Survey of anti-human T-cell leukemia virus type I antibody in family members of patients with adult T-cell leukemia

To evaluate the intrafamilial clustering of HTLV-I, we examined the sera or plasma of 296 healthy family members of patients with adult T-cell leukemia (ATL) for anti-HTLV-I antibodies. Of 296 subjects, 132 (44.6%) had anti-HTLV-I antibodies. Fifty-nine (41.0%) out of 144 males and 73 (48.0%) out of 152 females were seropositive. The positive rates of antibody to HTLV-I increased with age, especially between the 30-39 and the 40-49 age groups. Five out of 6 fathers, 3 out of 4 mothers, 31 (60.8%) out of 51 spouses, 40 (63.5%) out of 63 siblings and 46 (33.8%) out of 136 children of patients with ATL had anti-HTLV-I antibodies. Of 74 children with an ATL father, 14 (18.9%) were seropositive, while 32 (51.6%) out of 63 children with an ATL mother were seropositive. This difference was statistically significant (P less than 0.001). Of those children with an ATL father, 12 (26.1%) out of 46 whose mothers were HTLV-I carriers had antibodies to HTLV-I. In contrast, none of the 13 children whose mothers were not carriers were seropositive. These results supported the hypothesis that the mother-to-child transmission is one of the most important modes of HTLV-I transmission. In wives of male patients with ATL, the positive rate of antibody to HTLV-I was 65.6% (21/32), and in husbands of female patients, it was 52.6% (10/19). The high positive rate of antibody to HTLV-I not only in wives of male patients but also in husbands of female patients suggests that either HTLV-I is more frequently transmitted from wives to their husbands than we had originally expected, or that ATL may develop even in wives who acquire HTLV-I from their husbands after marriage.     

Adult T-Cell Leukemia/Lymphoma and Cluster of HTLV-I Associated Diseases in Brazilian Settings

We studied the transmission routes of human T-cell lymphotropic virus type I (HTLV-I) within families of 82 Brazilian patients diagnosed with adult T-cell leukaemia/lymphoma (ATL). Diagnosis of ATL in 43 male and 39 female patients was based on clinical and laboratory criteria of T-cell malignancy and detection of HTLV-I monoclonal integration. Samples were tested for HTLV antibodies and infection was confirmed as HTLV-I by Western Blot and/or polymerase chain reaction (PCR) assays. Overall 26/37 (70%) of mothers, 24/37 (65%) of wives, 8/22 (36%) of husbands, 34/112 (30%) of siblings and 10/82 (12%) offspring were HTLV-I infected. In 11 ATL patients, mothers were repeatedly HTLV-I seronegative, but HTLV-I pol or tax sequences were detected in 2 out of 6 cases tested by PCR. ATL patients with seronegative mothers related the following risk factors for HTLV-I infection: 6 were breast-fed by surrogate mothers with unknown HTLV-I status, 4 had a sexually promiscuous behaviour and 1 had multiple blood transfusions at a young age. Familial aggregation of ATL and other HTLV-I associated diseases such as HTLV-I myelopathy (HAM/TSP) and or uveitis, ATL in sibling pairs or in multiple generations was seen in 9 families. There were 6 families with ATL and TSP sibling pairs. In 3 families at least one parent had died with lymphoma or presenting neurological diseases and 2 offspring with ATL. Further to the extent of vertical and horizontal transmission of HTLV-I infection within ATL families, our results demonstrate that mothers who provide surrogate breast-milk appear to be an important source of HTLV-I transmission and ATL development in Brazil.     

Antibodies against p40tax gene product of human T-lymphotropic virus type-I (HTLV-I) under various conditions of HTLV-I infection

We investigated antibodies against pX gene product, p40tax, by ELISA using recombinant p40tax protein in HTLV-I seropositive carriers as well as patients with adult T cell leukemia (ATL) and HTLV-I-associated myelopathy (HAM). Seventy (49.0%) out of 143 HTLV-I healthy carriers were found to be positive for antibody against p40tax antigen and the follow-up samples at two-year intervals revealed constant reactivity by ELISA in each carrier. The onset of antibody production was delayed 4 to 12 weeks as compared with anti-HTLV-I in primary infection cases. The anti-p40tax-positive rate (90%) in HAM patients was significantly higher than that of healthy carriers, acute and chronic ATL patients and their family members. Furthermore, HAM patients and a few healthy carriers showed high reactivities by ELISA. Children from mothers with anti-p40tax showed a higher anti-HTLV-I-positive rate than that of children from mothers without anti-p40tax (54.5% versus 12.5%). Two men without anti-p40tax and one female with low anti-p40tax developed ATL during follow-up studies. These results suggest that HTLV-I carriers could be divided into 2 or 3 sub-populations according to antibody response to p40tax. A smaller population with anti-p40tax, especially a high antibody reactivity, could have a high risk of developing HAM and of transmission from mother to child. In addition, ATL may occur in a population with low or absent anti-p40tax.     

Antibodies against p40tax Gene Product of Human T-Lymphotropic Virus Type-I (HTLV-I) under Various Conditions of HTLV-I Infection

We investigated antibodies against pX gene product, p40^mx, by ELISA using recombinant p40^tax protein in HTLV-I seropositive carriers as well as patients with adult T cell leukemia (ATL) and HTLV-I-associated myelopathy (HAM). Seventy (49.0%) out of 143 HTLV-I healthy carriers were found to be positive for antibody against p40^tax antigen and the follow-up samples at two-year intervals revealed constant reactivity by ELISA in each carrier. The onset of antibody production was delayed 4 to 12 weeks as compared with anti-HTLV-I in primary infection cases. The anti-p40^tax-positive rate (90%) in HAM patients was significantly higher than that of healthy carriers, acute and chronic ATL patients and their family members. Furthermore, HAM patients and a few healthy carriers showed high reactivities by ELISA. Children from mothers with anti-p40^tax showed a higher anti-HTLV-I-positive rate than that of children from mothers without anti-p40^tax (54.5% versus 12.5%). Two men without anti-p40^tax and one female with low anti-p40^tax developed ATL during follow-up studies. These results suggest that HTLV-I carriers could be divided into 2 or 3 sub-populations according to antibody response to p40^tax. A smaller population with anti-p40^tax, especially a high antibody reactivity, could have a high risk of developing HAM and of transmission from mother to child. In addition, ATL may occur in a population with low or absent anti-p40^tax.     

Adult T-cell leukemia/lymphoma and cluster of HTLV-I associated diseases in Brazilian settings.

We studied the transmission routes of human T-cell lymphotropic virus type I (HTLV-I) within families of 82 Brazilian patients diagnosed with adult T-cell leukaemia/lymphoma (ATL). Diagnosis of ATL in 43 male and 39 female patients was based on clinical and laboratory criteria of T-cell malignancy and detection of HTLV-I monoclonal integration. Samples were tested for HTLV antibodies and infection was confirmed as HTLV-I by Western Blot and/or polymerase chain reaction (PCR) assays. Overall 26/37 (70%) of mothers, 24/37 (65%) of wives, 8/22 (36%) of husbands, 34/112 (30%) of siblings and 10/82 (12%) offspring were HTLV-I infected. In 11 ATL patients, mothers were repeatedly HTLV-I seronegative, but HTLV-I pol or tax sequences were detected in 2 out of 6 cases tested by PCR. ATL patients with seronegative mothers related the following risk factors for HTLV-I infection: 6 were breast-fed by surrogate mothers with unknown HTLV-I status, 4 had a sexually promiscuous behaviour and 1 had multiple blood transfusions at a young age. Familial aggregation of ATL and other HTLV-I associated diseases such as HTLV-I myelopathy (HAM/TSP) and or uveitis, ATL in sibling pairs or in multiple generations was seen in 9 families. There were 6 families with ATL and TSP sibling pairs. In 3 families at least one parent had died with lymphoma or presenting neurological diseases and 2 offspring with ATL. Further to the extent of vertical and horizontal transmission of HTLV-I infection within ATL families, our results demonstrate that mothers who provide surrogate breast-milk appear to be an important source of HTLV-I transmission and ATL development in Brazil.     

Epidemiological features of HTLV-I carriers and incidence of ATL in an ATL-endemic island: a report of the community-based co-operative study in Tsushima, Japan

To extend the epidemiological study on adult T-cell leukemia-lymphoma (ATL) in Japan, the geographical and demographic characteristics of carriers of human T-lymphotropic virus type I (HTLV-I) and patients with ATL were analyzed in Tsushima Island, which is one of the typical endemic areas of ATL in Kyushu, Japan. Even on the small island of Tsushima (710 km2; pop. 48,875; 123 villages), the positive rates of anti-HTLV-I antibody among the 58 villages studied varied from 2% to 50%, a fact that is probably associated with the historical events affecting the movement of the indigenous population of Tsushima Island. The positive rate of anti-HTLV-I antibody in males increased little with age; however, the female rate increased distinctly with age in moderate and high HTLV-I-endemic villages where more than 15% of the inhabitants had positive anti-HTLV-I antibody. Analysis of anti-HTLV-I antibody positivity between spouses confirmed that HTLV-I was more contagious from husband to wife than from wife to husband, which corresponded to the fact that the positive rate of anti-HTLV-I antibody in females older than 30 years was higher than that in males. Recently the rate of carrier children from HTLV-I carrier mothers was estimated at around 20%. The recent annual incidence rates of ATL among 1,000 HTLV-I carriers older than 40 years living in Tsushima Island was estimated at 2.2 in males, 0.8 in females.     

Concurrent Adult T-Cell Leukemia and Acute Myeloblastic Leukemia

A 49-year-old man developed adult T-cell leukemia (ATL) andacute myeloblastic leukemia (AML) at the same time. Using Southernblotting analysis, the leukemic cells of the ATL were foundto contain the human T-cdl leukemia virus type I (HTLV-I) proviralgenome, whereas those of the AML did not, indicating the HTLV-Inot to be associated with the AML oncogenesis. At the initialpresentation, the serum anti-HTLV-I antibody was judged on screeningby a routine particle-agglutination (PA) test and an indirectimmunofluorescence assay (IF) to be negative. By Western blottinganalysis, however, the serum was proved to be positive for anti-HTLV-Iantibody. These results indicate that a routine PA-test andan IF way show false negative reactions on very rare occasionsof low antibody titer. This is the first report of a coincidenceof ATL with another type of leukemia.     

Mother-to-child transmission of human T-cell leukemia virus type I (HTLV-I): a fifteen-year follow-up study in Okinawa, Japan

Okinawa prefecture is one of the endemic areas for adult T-cell leukemia/lymphoma (ATLL) in Japan. In this study, 2,013 serum specimens drawn serially over a period of 15 years (1968-1983) from 311 mother/child pairs in Okinawa were tested for antibodies to human T-cell leukemia virus type I (HTLV-I) by enzyme-linked immunosorbent assay and by indirect immunofluorescence. The prevalence rate of HTLV-I antibodies was 20.9% (65 cases) in the mothers and 3.2% (10 cases) in the children. Of the 65 seropositive mothers, 10 (15.4%) had seropositive children. This study revealed a significant difference between the prevalence rates of HTLV-I antibodies in mothers and children. In addition, children born to seropositive mothers had acquired their HTLV-I antibodies by the age of 3 years, and were still seropositive at the age of 18 years. No initially seronegative child was found to have seroconverted during the period investigated.     

Immunodeficiency in Preclinical Smoldering Adult T-Cell Leukemia

We treated two Japanese patients with Pneumocystis carinii pneumonia.Inclusion bodies in both adrenal glands of patient no. 1 indicateda herpesvirus infection. The patient no. 2 recovered from thepneumonia upon sulfametoxazole-trimethoprim medication and high-dosemethylprednisolone therapy. In both patients, anti-human T-cellleukemia virus type I (HTLV-I) antibodies were positive andanti-human immunodeficiency virus antibodies were negative.Peripheral leukocytes in patient no. 1 numbered 13.6 x 10³/µlwith 25% morphologically normal lymphocytes and 4% abnormal.Lymphocyte surface markers were 72.6%, CD4+, 13.6% CD8+ and46.4% CD3+. In patient no. 2, leukocytes numbered 13.8 x 10³/µl,including 18% lymphocytes, although no morphologically abnormallymphocyte was evident. Lymphocyte markers were 36.6% CD4+,16.8% CD8+ and 46.6% CD3+. Monoclonal integration HTLV-I proviralDNA in lymphocytes of patient no. 2 was demonstrated by Southernblotting. Thus, both patients must have had smoldering adultT-cell leukemia (ATL) without any cutaneous involvement, whereasthe morphological diagnosis from peripheral blood smears wasone of HTLV-I carrier status with a few atypical lymphocytes,i.e., the preclinical state of smoldering ATL. Pneumocystiscarinii infectious, a viral infection of the adrenals (no. 1),negative purified protein derivatives of the tuberculin reactionand suppressed blastogenesis of the peripheral lymphocytes indicatedHTLV-I-induced impairment of the immune mechanism to have alreadyoccurred in both patients without there being a vast proliferationof ATL cells.     

Clinicopathological Features of Adult T-Cell Leukemia with CD30 Antigen Expression

Recently, several cases of adult T-cell leukemia (ATL) with CD30 antigen have been reported, but its clinical significance remains unknown. Accordingly, we studied CD30 antigen expression in ATL cases and documented the clinicopathological characteristics of these cases.

Immunohistochemical and clinical characteristics were studied in 46 patients with malignant lymphoma or benign lesions of lymphoid tissue, who had antibodies against human T-cell leukemia virus type I (HTLV-I). Monoclonal integration of HTLV-I provirus was demonstrated in the tumor cells in 36 (ATL) of the 46 cases. CD30 antigen expression was evident in seven of these 36 cases (19.4%), however it was not seen in any of the ten cases lacking the integration of HTLV-I provirus. A comparison of ATL cases with and without CD30 antigen expression revealed significantly larger numbers of abnormal lymphocytes in the peripheral blood and lower serum calcium levels in ATL expressing CD30 antigen.     

The prevalence of human T-cell leukemia virus type I infection in patients with hematologic and nonhematologic diseases in an adult T-cell leukemia-endemic area of Japan

In order to clarify the prevalence of human T-cell leukemia virus type I (HTLV-I) infection in the Kagoshima district, Japan, a highly endemic area for HTLV-I, antibodies for HTLV-I (anti-HTLV-I) were examined in the sera of 6167 from healthy residents and patients with various hematologic and nonhematologic diseases. In healthy residents, including blood donors, the prevalence of anti-HTLV-I was 11.9% (562/4741 persons). The prevalence increased with age, and was significantly higher in in females than in males (P less than 0.01). The prevalence of anti-HTLV-I in blood donors was 8.5%. In In hematologic diseases, the prevalence of anti-HTLV-I was 98.3% in ATL, 28.9% in lymphoproliferative disorders except ATL, and 10.6% in myeloproliferative disorders. In nonhematologic diseases, the prevalence of anti-HTLV-I was shown to be 29.5% in pulmonary tuberculosis, 25.8% in leprosy, 33.8% in chronic renal failure (CRF), 21.9% in autoimmune diseases, and 47.8% in strongyloidiasis. The various diseases except myeloproliferative disorders had significantly higher prevalence of anti-HTLV-I than healthy residents (P less than 0.01 or 0.05). For autoimmune diseases, the prevalence of anti-HTLV-I in patients with blood transfusion (55.6%) was higher than in those without blood transfusion (8.7%), and healthy residents. In hemodialysis patients with CRF who had received blood transfusions the prevalence of anti-HTLV-I increased with the number of blood transfusions. Therefore, HTLV-I transmission via blood transfusion would partially explain these high prevalence of anti-HTLV-I. However, the prevalence of anti-HTLV-I in hemodialysis patients with CRF was statistically higher than that in healthy residents, regardless of blood transfusion (P less than 0.01). Furthermore, hemodialysis patients showed significantly higher prevalence of anti-HTLV-I than healthy residents, even at a younger age. Patients with pulmonary tuberculosis and leprosy showed the same results as hemodialysis patients. These results suggest that possibility that HTLV-I infection has some relation not only to ATL but also to other diseases. Therefore, it seems very important to halt the spread of HTLV-I transmission as soon as possible.     

Intrafamilial transmission of HTLV-I and its association with anti-Tax antibody in an endemic population in Japan

To assess the relationship of anti-Tax antibody to human T-cell lymphotropic virus type-I (HTLV-I) transmission, the sero-prevalence of HTLV-I was analyzed among married couples and among mother/child (both adults) pairs. HTLV-I seroprevalence was significantly higher among wives with anti-Tax⁺ than those with anti-Tax⁻ HTLV-I carrier husbands (82.4% vs. 59.5%). However, in the group of wives aged 60 years or older, there was no statistical difference in HTLV-I seropositivity based on the husbands' anti-Tax sero-status. In the group whose wives were less than 60 years old, more anti-Tax sero-positive than sero-negative husbands had high DNA levels (57.1% and 20.0%), whereas in the group of husbands whose wives were aged 60 years or older, the number of anti-Tax sero-positive and sero-negative individuals with high DNA levels was similar. HTLV-I sero-prevalence was significantly higher among the adult men with anti-Tax⁺ carrier mothers than those with anti-Tax⁻ carrier mothers (52.0% vs. 14.3%). For women, HTLV-I sero-prevalence did not differ significantly according to their mothers' anti-Tax sero-status. Our results suggest that the presence of anti-Tax antibody in HTLV-I carriers is an age-dependent risk factor for male-to-female HTLV-I transmission. Furthermore, the effect of the mother's anti-Tax antibody as a risk factor for vertical HTLV-I transmission could be observed in men even after becoming adults. Int. J. Cancer 75:15–18, 1998.© 1998 Wiley-Liss, Inc.     

Detection of HTLV-I Genome in Seronegative Infants Born to HTLV-I Seropositive Mothers by Polymerase Chain Reaction

We applied the polymerase chain reaction (PCR) method to detect gag, env and pX sequences of human T cell leukemia virus type I (HTLV-I) provirus in peripheral blood lymphocytes of seronega-tive infants born to HTLV-I seropositive mothers. Out of 22, five subjects were found to contain the HTLV-I provirus genome. Two of the five cases were judged to be negative for not only anti-HTLV-I antibodies but also the viral antigens on cultivated lymphocytes by the conventional antibody/antigen detection methods. These results indicate that PCR is of great use as a simple and highly sensitive method detect HTLV-I infection.     

Detection of HTLV-I genome in seronegative infants born to HTLV-I seropositive mothers by polymerase chain reaction

We applied the polymerase chain reaction (PCR) method to detect gag, env and pX sequences of human T cell leukemia virus type I (HTLV-I) provirus in peripheral blood lymphocytes of seronegative infants born to HTLV-I seropositive mothers. Out of 22, five subjects were found to contain the HTLV-I provirus genome. Two of the five cases were judged to be negative for not only anti-HTLV-I antibodies but also the viral antigens on cultivated lymphocytes by the conventional antibody/antigen detection methods. These results indicate that PCR is of great use as a simple and highly sensitive method detect HTLV-I infection.     

Serological study of the antibody to the adult T-cell leukemia-virus-associated antigen in various hematological diseases

A serological study of antibody to adult T-cell leukemia-virus-associated antigen (anti-HTLV-I antibody) was made in 170 cases of various hematological diseases at Shikoku Cancer Center Hospital. The titer of anti-HTLV-I antibody was determined by indirect immunofluorescence using the MT-2 cell line. Two of two patients with ATL were positive for antibody. In non-Hodgkin's lymphoma, six of 18 cases of T-cell phenotype were positive (33%), while two of 29 cases of B-cell phenotype were antibody-positive (7%). Some cases of leukemia and aplastic anemia, who had received multiple blood transfusions, were found to be seropositive. Our results suggest that anti-HTLV-I antibody may be related to non-Hodgkin's lymphoma with T-cell phenotype as well as ATL.     

Differences Between Long- and Short-Term Survivors with Lymphoma Type of Adult T-Cell Leukemia

The clinical features at time of diagnosis of long-term survivors with lymphoma type of adult T-cell leukemia (ATL) were compared with those of short-term survivors. We had 51 Japanese patients with lymphoma type of ATL from 1981 to 1989 who had human T-cell leukemia virus type I (HTLV-I) antibody and monoclonal integration of HTLV-,I proviral DNA in the malignant cells. Of the 51 patients, 7 survived for more than 3 years, and they were classified as long-term survivors. Twenty-four patients died within 1 year and they were classified as short-term survivors. Differences between these two groups were investigated with the clinical findings recorded at the time of diagnosis. Findings that proved significant were serum lactate dehydrogenase (LDH) levels, calcium, total protein levels and the presence of B symptoms. Patients with lymphoma type of ATL are expected to be long-term survivors if they have no hypercalcemia or B symptoms with only mildly elevated serum LDH and total protein levels.     

Novel Interleukin-2 Dependent T-Cell Line Derived from Adult T-Cell Leukemia Not Associated with Human T-Cell Leukemia Virus Type I

A novel interleukin-2 (IL-2)-dependent T-cell line, WHN2, was established from a patient with adult T-cell leukemia (ATL) not associated with human T-cell leukemia virus type I (HTLV-I). Neither the original leukemic cells nor the WHN2 cells showed proviral integration in their cellular DNAs by Southern blot analysis. The surface phenotype showed that both the original leukemic cells and the WHN2 cells had a common phenotype of ATL, i.e., positive for CD2, CD4, human leukocyte antigen DR (HLA-DR) and CD25, but negative for CD8, a characteristic of helper/inducer T-cells. Most of the chromosomal abnormalities of the original leukemic cells were maintained in the WHN2 cell line. Furthermore, Southern blot analysis of the T-cell receptor β -chain gene rearrangement revealed that the original leukemic cells and WHN2 cell line had identical patterns, suggesting that the WHN2 cell line was truly derived from the original leukemic cells. Dose-dependent growth on IL-2 was demonstrated, and at the maximal stimulation, the number of cells doubled within three days. This IL-2-dependent growth was inhibited by the simultaneous existence of anti-IL-2 receptor a and β chain antibodies. These results indicate that the character of the WHN2 cell line is similar to that of the cell lines derived from ATL associated with HTLV-I. Thus, the HTLV-I-negative ATL cell line, WHN2, should be useful in the comparative study of the pathogenesis of ATL associated with or without HTLV-I.     

Human T-cell leukemia virus type I infection in hemodialysis patients

Human T-cell leukemia virus Type I (HTLV-I) has been detected in a high proportion of individuals in Kumamoto prefecture (Kyushu) and Okinawa, where adult T-cell leukemia (ATL) is more likely to occur. The seroprevalence of antibody to HTLV-I was evaluated in hemodialysis patients and healthy individuals in the ATL endemic area. The prevalence of antibody to HTLV-I in 13,329 healthy controls was 3.6%, compared with 19.7% in 949 chronic hemodialysis patients. The prevalence of hemodialysis patients was significantly higher (P less than 0.01) than that in healthy individuals. Of 681 blood transfused patients who had undergone hemodialysis, 153 (22.5%) were seropositive, compared with 34 (12.7%) of the 268 who had not received the blood transfusion. The incidence was higher in dialysis patients who had been transfused than in those who had never received blood transfusions. Immune defects associated with uremia may have predisposed the patients to HTLV-I infection. Repeated antigenic stimulation from multiple infectious agents may have also played a role. The findings suggest an association between maintenance hemodialysis and HTLV-I infection, which can not be explained solely by blood or blood products.     

HTLV-I carriers among migrants from an ATL-endemic area to ATL non-endemic metropolitan areas in Japan

The prevalence of antibodies against HTLV-I among Kyushu natives aged 16 to 39 years who moved from Nagasaki and Kagoshima prefectures to Aichi prefecture (a non-endemic area for ATL) was compared by their cities or counties of birth. The positive rate of anti-HTLV-I antibody was 2.4% (II/400) among Nagasaki natives, 6.4% (20/312) among Kagoshima natives and 4.0% (31/772) for both combined. There was a slight difference in the positive rate of anti-HTLV-I antibody between Kyushu natives from cities (3.3%) and from counties (4.5%). In county areas, the prevalence of anti-HTLV-I antibodies among migrants from areas of relatively higher mortality for malignant lymphomas (7.5%) was significantly higher (p less than 0.01) than among persons from lower mortality areas (1.9%). Most "positive" persons had moved from Kyushu to Aichi prefecture between the ages of 15 and 18 years. The results of the present study suggest that: there is a considerable number of HTLV-I carriers among Kyushu natives who have settled in ATL non-endemic areas, especially among those born in regions of Kyushu district which have a high mortality rate for malignant lymphomas; and that Kyushu natives who had settled in metropolitan areas might have been exposed to HTLV-I during childhood in their birthplace.     

Antigenic variations of retrovirus in Japanese cancer patients

Previously we demonstrated the prevalence of human T lymphotropic virus type I (HTVL-I) infection among cancer patients in Japan. This study was carried out to examine antigenic properties of retroviruses prevalent among Japanese cancer patients. Sera of 126 Japanese patients with cancer of different organs and with no history of blood transfusion, 94 in adult T cell leukemia (ATL)-endemic area and 32 in ATL-nonendemic area, were surveyed for antibodies to HTLV-I and HTLV-II by enzyme-linked immunosorbent assay (ELISA), Western blot analysis, and indirect immunogold electron microscopy. Among patients who were seropositive to HTLV-I, 39 of 56 (69.6%) in ATL-endemic area and 9 of 9 (100%) in ATL-nonendemic area were seropositive also to HTLV-II. Of 48 sera positive to both HTLV-I and HTLV-II, 34 (70.8%) showed stronger reactivities to HTLV-I than to HTLV-II. Among patients who were seronegative to HTLV-I, 3 of 38 (7.9%) in ATL-endemic area and 5 of 23 (21.7%) in ATL-nonendemic area were seropositive to HTLV-II. Antibodies appearing and disappearing in sera of patients examined during the clinical course reacted with peptide species of HTLV-I and/or HTLV-II not always consistent with peptide species cross-reactive between HTLV-I and HTLV-II. These results indicate the antigenic diversity of retroviruses prevalent among Japanese cancer patients.