ANCA-associated vasculitis (AAV) Geographic factors: the latitude of Japan Japan is located between the latitudes of 26–45°N. Asahikawa city (43.5°N) on Hokkaido Island is close to the latitude of Lugo, Spain (42°N) [1]. On this island, there are more patients with microscopic polyangiitis (MPA); a higher number of patients with AAV are Selleckchem PLX 4720 MPO-ANCA-positive than granulomatosis with polyangiitis (GPA)- or pronase 3 (PR3)-positive [1]. These data are compatible with the latitude theory of AAV [3] (Fig. 1). Fig. 1 Geographical differences in the incidences of vasculitides. GCA and GPA occur more frequently in North Europe and North America whereas Takayasu arteritis and MPA

occur more frequently in Japan On the other hand, it is interesting to note that a study from Beijing (39.5°N), China,

demonstrated that 60.7 % (54/89) of patients with GPA were MPO-ANCA-positive and 38.2 % (34/89) were PR3-ANCA-positive. Patients with MPO-ANCA had multiorgan involvement with higher serum creatinine levels than PR3-ANCA-positive patients with GPA [9]. Differences in clinical phenotypes Differences in renal involvement in GPA and MPA between patients in the UK and Japan were reported by Watts et al. [10]. Supporting data indicated that patients with localized GPA were more frequent than GPA patients with renal involvement in Japan, which was reported by Harabuchi et al. from Asahikawa Medical University and confirmed in our investigation [11]. Another report by certain otolaryngologists reached the same conclusion [12]. Moreover, two studies Oxaprozin demonstrated renal involvement in 12–40 % of 21 patients with LEE011 mw GPA [13, 14]. In another hospital-based, nationwide, retrospective study conducted in Japan from 1988 to 1998 by the Japanese Ministry of Health, Labour and Welfare, renal involvement was diagnosed in 39–63 % of 172 patients. In two studies by Gross et al. in Germany and Hoffman et al. in the USA, renal involvement was diagnosed in 77 % of 155 patients and 77 % of 70 patients with GPA, respectively [15, 16]. Genetic factors A genetic analysis of patients with MPA was initiated in 1997 by the Research Committee of Intractable Vasculitis of

the Japanese Ministry of Health and Welfare (Chief Investigator Prof. Hiroshi Hashimoto). A significant association between HLA-DRB1*0901 and MPA (P = 0.037; odds ratio [OR] 2.44; 95 % CI 1.33–4.46) as well as MPO-ANCA positivity (P = 0.014; OR 2.44; 95 % CI 1.41–4.22) was demonstrated by Tsuchiya et al. [17, 18]. Another report published in 1996 demonstrated an association between HLA-DR9 in 62.5 % patients and cANCA-positive GPA (10/16) compared with 26 % in healthy controls (P < 0.05) [19]. The decreased activation potential of natural killer cells and/or T cells associated with killer cell immunoglobulin-like receptor or HLA genotypes was demonstrated in patients with MPA, thus suggesting that these patients may have insufficient resistance to infections.