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Letters

Association of human
T lymphotropic virus type Iwith Sjögren syndrome
Sjögren syndrome (SS) is an autoimmune disease caused by a
combination of genetic and environmental factors. The mostimportant environmental factor is viral infection. The retrovirus
human T lymphotropic virus type I (HTLV-I) is deemed as an
SS pathogen, because anti-HTLV-I antibodies were positive in
23% of patients with SS but only in 3.4% of control subjects(blood donors).1 The patients with SS in that study, however,were limited to those who visited the hospital, and the control
is not screened for SS, a bias may have been present. Thus, inthe present study, we measured anti-HTLV-I antibodies in 852
Nagasaki atomic bomb survivors who had previously been
screened for SS.
Between November 2002 and October 2004, 1008 Nagasaki
atomic bomb survivors who had been followed biennially since
1958 at the Radiation Effects Research Foundation (RERF),2
answered a questionnaire concerning ocular and oral symptoms
and were screened for anti-SS-A/Ro, anti-SS-B/La antibodies
and rheumatoid factor. We then examined them for SS using
American–European Consensus Group criteria3 and its modiﬁcations, including the tear ﬂow test (Schirmer-I test), salivary ﬂow
test (Saxon test), cornea and conjunctiva staining test, salivary
ultrasonography and salivary MRI.4 We found 23 SS cases, a prevalence of 2.3%.4 From April 2006 to June 2008, 852 participants(18 with SS, 335 men and 517 women, average age 71.1 years)
underwent HTLV-I antibody measurements. RERF’s Human
Investigation Committee reviewed and approved the study protocol, and all participants provided written informed consent.
Of the 852 participants, 75 (8.8%) were anti-HTLV-I antibody
positive by chemiluminescent enzyme immunoassay (Fujirebio,Tokyo, Japan) and western blotting (BML, Tokyo, Japan). A
total of 5 (6.7%) of the seropositive subjects and 13 (1.7%) of
the seronegative subjects were diagnosed as having SS. In all,5 (27.8%) of the 18 SS participants and 70 (8.4%) of the 834
non-SS participants had anti-HTLV-I antibodies (p=0.016, Fisher
exact test). Prevalence of women (57/75, 76%, 460/777, 59%,p=0.005) and positive anti-SS-A/Ro antibodies (7/75, 9.3%,23/777, 3.4%, p=0.020) and titre of rheumatoid factor (9.8 U/ml, 7.7 U/ml, p=0.038) were also signiﬁcantly higher among
HTLV-I seropositive group than seronegative group. The ﬁndingthat HTLV-I infection was predominant in women may partly
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Table 1 Characteristics of Sjögren syndrome (SS) according toanti-human T lymphotropic virus type I (HTLV-I) antibody statusMean±SD age, years
Sex (male:female)
Sicca symptoms, N (%)
Dry eye signs, N (%)
Dry mouth signs, N (%)
Anti-SS-A Ab, N (%)
Anti-SS-B Ab, N (%)
Anticentromere Ab, N (%)
Extraglandular manifestations, N (%)
Secondary SS, N (%)
RF positive, N (%)

HTLV-I positive
SS (n=5)

HTLV-I negative
SS (n=13)71.4±5.8
0:5
4 (80)
5 (100)4 (80)
4 (80)
1 (20)0 (0)3 (60)
1 (20)0 (0)71.7±5.6
3:10
9 (69)
9/9* (100)
10 (77)
10 (77)
3 (23)
2/12* (17)
2 (15)
2 (15)
4 (31)*Number was reduced because not all the participants agreed to take full examinations.
Ab, antibodies; RF, rheumatoid factor.

explain the predominance of SS in women. The prevalence ofSS-B/La antibodies was similar for the two groups (1/75, 1.3%,7/777, 0.9%). An age-adjusted and sex-adjusted OR of having
SS for those in the HTLV-I seropositive group was 3.68 (95%CI, 1.26 to 10.75, p=0.014) by a linear logistic model. That suggests a possible association between HTLV-I infection and SS asreported in previous immunological studies.5–7
The prevalence of sicca symptoms, signs and positive autoantibodies was similar between the HTLV-I positive and negative
SS groups (table 1). The frequency of extraglandular manifestations tended to be higher in HTLV-I seropositive group than in
HTLV-I seronegative group (table 1), which supports the previous report.8
Our results suggest that the association between HTLV-I andSS is mediated through anti-SS-A/Ro antibodies, because theassociation between being anti-HTLV-I antibody positive and SS
disappeared when anti-SS-A/Ro antibodies were incorporated
in the analysis (data not shown). While genetic and environmental factors interact in the development of SS, HTLV-I may be animmune-activating pathogen for SS through anti-SS-A/Ro antibody production. Further studies are needed to conﬁrm this.
All participants in the present study were atomic bomb survivors, but no association has been reported between radiation dose and either SS4 or HTLV-I infection,9 nor did we ﬁnda signiﬁcant association between radiation dose by DS0210 andHTLV-I in the present study. Thus, our data should be generalisable to the Japanese population.
In this ﬁrst epidemiological study of measuring anti-HTLV-I
antibodies in SS and non-SS participants, we conﬁrmed theAnn Rheum Dis November 2010 Vol 69 No 11

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Letters
association between HTLV-I infection and SS or anti-SS-A/Ro
antibodies.

Competing Interests None.
Accepted 6 February 2010
Ann Rheum Dis 2010;69:2056–2057. doi:10.1136/ard.2010.128736

Ayumi Hida,1 Misa Imaizumi,1 Nobuko Sera,1 MasazumiAkahoshi,1 Midori Soda,1 Renju Maeda,1 Eiji Nakashima,2 HidekiNakamura,3 Hiroaki Ida,3 Atsushi Kawakami,3 Katsumi Eguchi3
1Department of Clinical Studies, Radiation Effects Research Foundation, Nagasaki, Japan
2Department of Statistics, Radiation Effects Research Foundation, Hiroshima, Japan
3Unit of Translational Medicine, Department of Immunology and Rheumatology,

Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Correspondence to Dr Ayumi Hida, Department of Clinical Studies, Radiation
Effects Research Foundation, 1-8-6 Nakagawa, Nagasaki 850-0013, Japan;
ayumih@rerf.or.jp
Acknowledgements The authors would like to thank Mr Shinichiro Ichimaru
for data preparation, Ms Kaoru Yoshida and Mr Tomohiro Ikeda for generalassistance, and Dr Miriam Bloom (SciWrite Biomedical Writing & Editing
Services) for professional editing.
Funding The Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki,
Japan, is a private, non-profit foundation funded by the Japanese Ministry of Health,Labour and Welfare and the US Department of Energy, the latter in part through theNational Academy of Sciences. This publication was supported by RERF ResearchProtocols B27-02 and B43-06 and Grant-in-Aid number 15790516 from the Japanese
Ministry of Education, Culture, Sports, Science and Technology.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the HumanInvestigation Committee in Radiation Effects Research Foundation.
Provenance and peer review Not commissioned; externally peer reviewed.

Ann Rheum Dis November 2010 Vol 69 No 11

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