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Am. J. Trop. Med. Hyg., 76(2), 2007, pp. 384-391
Copyright © 2007 by The American Society of Tropical Medicine and Hygiene

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ANTIBODY ISOTYPE RESPONSES TO PARAMYOSIN, A VACCINE CANDIDATE FOR SCHISTOSOMIASIS, AND THEIR CORRELATIONS WITH RESISTANCE AND FIBROSIS IN PATIENTS INFECTED WITH SCHISTOSOMA JAPONICUM IN LEYTE, THE PHILIPPINES

TAKESHI NARA*, KYOICHI IIZUMI, HIROSHI OHMAE, ORLANDO S. SY, SOICHI TSUBOTA, YUTAKA INABA, AKIKO TSUBOUCHI, MASANOBU TANABE, SOMEI KOJIMA, AND TAKASHI AOKI
Department of Molecular and Cellular Parasitology and Department of Epidemiology and Environmental Health, Juntendo University School of Medicine, Tokyo, Japan; Laboratory of Imported Parasitic Diseases, Department of Parasitology, Institute of Infectious Diseases, Tokyo, Japan; Schistosomiasis Research Hospital, Palo, Leyte, The Philippines; Department of Tropical Medicine and Parasitology, School of Medicine, Keio University, Tokyo, Japan; Center for Medical Sciences, International University of Health and Welfare, Tochigi, Japan

We examined whether antibody isotype responses to paramyosin (PM), a vaccine candidate for schistosomiasis, are associated with age-dependent resistance and pathology in liver fibrosis using human sera collected from 139 individuals infected with Schistosoma japonicum in Leyte, The Philippines. We report that IgA and IgG3 responses to PM showed a positive correlation with age and that the epitopes responsible were localized predominantly within the N-terminal half of PM. In addition, the IgG3 response to PM was associated with serum level of procollagen-III-peptide (P-III-P), an indicator of progression of liver fibrosis. These results imply that IgG3 against PM may not only provoke age-dependent resistance to S. japonicum infection but also enhance liver fibrosis. In contrast, levels of IgE to PM and to multiple PM fragments showed a negative correlation with P-III-P level. Thus, in contrast to IgG3, increases in PM-specific IgE may contribute to suppression of liver pathogenesis in schistosomiasis.

Received February 22, 2006. Accepted for publication September 28, 2006.

Acknowledgments: We sincerely thank all patients for their willingness to participate in this study and Schistosomiasis Research Hospital staffs at Palo, Leyte, The Philippines, for their technical assistance.

Financial support: This work was supported in part by grants-in-aid for scientific research (Nos. 15390138, 15659102, 17590377, and 17390123) from the Ministry of Education, Science, Sports, Culture, and Technology of Japan, from the Ohyama Health Foundation (to Takeshi Nara), and from the Kampou Science Foundation (to Takeshi Nara). Takashi Aoki was supported by a Grant-in-Aid for the 21st Century Center of Excellence Research from the Ministry of Education, Science, Sports, Culture, and Technology of Japan.

* Address correspondence to Takeshi Nara, Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan. E-mail: tnara{at}med.juntendo.ac.jp

Authors’ addresses: Takeshi Nara, Kyoichi Iizumi, Soichi Tsubota, Akiko Tsubouchi, and Takashi Aoki, Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan, Telephone: 81-3-5802-1043, Fax: 81-3-5800-0476, E-mail: tnara{at}med.juntendo.ac.jp. Hiroshi Ohmae, Laboratory of Imported Parasitic Diseases, Department of Parasitology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan. Orlando S. Sy, Schistosomiasis Research Hospital, Palo, Leyte, The Philippines. Yutaka Inaba, Department of Epidemiology and Environmental Health, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan. Masanobu Tanabe, Department of Tropical Medicine and Parasitology, School of Medicine, Keio University, Tokyo 160-8582, Japan. Somei Kojima, Center for Medical Sciences, International University of Health and Welfare, Kitakanamaru 2600-1, Otawara, Tochigi 324-8501, Japan.

Reprint requests: Takeshi Nara, Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.




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Copyright © 2007 by the American Society of Tropical Medicine and Hygiene.