Comparison of immunological and histopathological changes between oral and intraperitoneal immunization of outer membrane of Haemophilus parainfluenzae antigens in mice

IgA nephropathy (IgAN) was first reported by Berger in 1968, and characterized by diffuse IgA deposits in glomerular mesangium and mesangial proliferative glomerulonephritis. Clinically, patients with IgAN have frequently episodic macroscopic haematuria accompanied with pharyngitis, tonsillitis, gastroenteritis, bronchitis, or sinusitis. These findings suggest that IgAN is related to inflammatory and immune responses to mucosal infections. We have reported that primary IgAN patients with acute onset are often associated with mucosal infections such as pharyngitis and tonsillitis, and Haemophilus parainfluenzae (HP) is more frequently isolated from the pharynx of patients with IgAN than from those with other diseases.1 We also demonstrated glomerular deposition of outer membrane of HP (OMHP) antigens and the presence of IgA antibody against OMHP in patients with IgAN.1 These findings suggest that HP has a role in the aetiology of primary IgAN. In the present study, we attempt to develop an experimental model of IgAN induced by oral and intraperitoneal immunization of OMHP antigens, and evaluate the difference in immunological and histopathological changes between these two administration routes. Four-week-old female C3H/HeN mice were fed mouse chow. One hundred and twenty mice were divided into oral (PO group) and intraperitoneal (IP group) administration groups of OMHP antigens and each control groups. Mice of the PO group received OMHP antigens for daily drinking water and intragastric intubation once a week, and mice in the IP group received intraperitoneal injection of 0.1 mL of OMHP antigens, once a week. Six mice from each group were killed at 10, 20, 30, 40 and 50 weeks of age to examine sequential glomerular changes. We also measured serum IgG, IgA, IgM antibody against OMHP antigens, and serum IL-10 and IFN γ by ELISA. Throughout experiments, haematuria and proteinuria were analysed every 5 weeks. IgA antibodies against OMHP significantly increased in PO and IP groups compared with the control, and the degree of increase in IgA antibodies against OMHP was more prominent in the PO group. In the IP group, IgG and IgM antibodies against OMHP increased more markedly. Glomerular deposition of IgA and increase of mesangial matrix were observed in the PO group from 40 weeks of age and in the IP group from 30 weeks of age, respectively. Mice in both groups showed glomerular deposition of OMHP antigens. Haematuria was not detected in any group. Serum IL-10 tended to increase in the PO and IP groups, and IFN γ did not increase significantly in any group. These results suggest that oral administarion of OMHP antigens induce glomerular deposition of IgA and mesangial proliferation with increase of IgA antibodies against OMHP antigens in mice, and these observations in the PO group resemble the changes of human IgAN more closely than in the IP group.