CONTEMPORARY CHALLENGES IN AUTOIMMUNITY Antitreponemal Antibodies Leading to Autoantibody Production and Protection from Atherosclerosis in Kitavans from Papua New Guinea Nancy Agmon-Levin, a,b, ∗ Porat Katz Bat-sheva, b,c, ∗ Ori Barzilai, b Maya Ram, b Staffan Lindeberg, d Johan Frosteg˚ ard, e and Yehuda Shoenfeld a,b,f a Department of Medicine “B” and b Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel c Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel d Department of Medicine, Lund University, Lund, Sweden e Department of Medicine, Karolinska University Hospital, Huddinge, Stockholm, Sweden f Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel The objective of our study was to determine the prevalence of anti-infectious agent antibodies and autoantibodies in a unique non-Westernized population from Kitava, Papua New Guinea (PNG), compared to Western populations. We matched 120 serum samples from Kitavans with 437 samples from four healthy control groups. Sera were tested for the presence of anti-infectious agent antibodies (treponema, toxoplsmo- sis, Epstein–Barr virus, cytomegalovirus, rubella) and autoantiobodies [anti-double- stranded (ds)DNA, anti-chromatin, anti-ribonucleoprotein (RNP), anti-SSB, anti-SSA, anti-Scl-70, anti-Smith, anti-centromer, anti-SmRNP, anti-Jo-1, and anti-ribosomal-P] using the Bio-Rad BioPlex 2200. Antitreponemal antibodies were detected in 87% of PNG sera versus 0–6% of controls (P < 0.0001). Anti-dsDNA antibodies were detected in 31% of PNG samples, which was significantly higher than in three of the control groups (<10%). The outstanding high rate of antitreponemal antibodies detected in Kitavans possibly represents prior yaws disease. A low prevalence of cardiovascular disease was previously documented in Kitavans and has been attributed, in addition to their diet, to the high prevalence of natural cardioprotective autoantibodies (the IgM- antiphosphorylcholine antibodies) in this population. Treponemal infection has been shown to induce the appearance of antiphosphorylcholine antibodies. These protective autoantibodies may cross-react with the pathogenic anti-dsDNA antibodies. Thus, it is suggested that infection with treponema is associated with the presence of protective as well as pathogenic autoantibodies. Key words: Papua New Guinea; Kitava; treponema; antiphosphorylcholine antibodies; atherosclerosis; autoantibodies; yaws disease Address for correspondence: Yehuda Shoenfeld, M.D., F.R.C.P., De- partment of Medicine “B” and Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel. Voice: +972-3- 5302652; fax: +972-3-5352855. shoenfel@post.tau.ac.il ∗ Both authors have equally contributed. Introduction The island of Kitava in Papua New Guinea (PNG) hosts a genetically homogenous culture which has not been affected by modern habits. A series of studies conducted by Lindeberg and Contemporary Challenges in Autoimmunity: Ann. N.Y. Acad. Sci. 1173: 675–682 (2009). doi: 10.1111/j.1749-6632.2009.04671.x c  2009 New York Academy of Sciences. 675