Experimental IgA nephropathy induced by Haemophilus parainfluenzae antigens

Abstract

IgA nephropathy(IgAN) was first reported by Berger in 1968, and characterized by diffuse IgA deposition in mesangium. Patients with IgAN have usually episodic macroscopic hematuria accompanied with pharingitis, gastroenteritis, bronchitis, or sinusitis. These findings suggest that IgAN is an immune-complex disease resulting from a poorly controlled mucosal immune response to environmental antigens to which the patients were chronically exposed. We reported glomerular deposition of outer membrane of Haemophilus parainfluenzae (OMHP) antigens and the presence of IgA antibody against OMHP in the sera of patients with IgAN. 1 These suggest that Haemophilus parainfluenzae has a role in the etiology of this disease. Furthermore, Endo et al. reported experimental IgA nephropathy induced by Gram-negative bacteria. 2 This study was conducted to determine whether intraperitoneal administration of OMHP antigens induced immunohistologically evident glomerular deposition of IgA and C3 in C3H/HeN mice.Female C3H/HeN mice (4 weeks old) were fed on commercial pellet mouse foods. The mice received intraperitoneal injection of OMHP antigens, once per week (OMHP group). The control group received intraperitoneal injection of PBS. The mice were killed at 10, 20 and 30 weeks after the experiment commenced. Throughout the experiments, hematuria and proteinuria were analyzed every 5 weeks.The OMHP group showed glomerular deposition of IgA, C3 and OMHP antigens, glomerular changes (mesangial hypercellularity and increase of mesangial matrix) at 20 and 30 weeks. The control group showed no glomerular deposition of IgA, C3 and OMHP antigens and no glomerular change. Hematuria was recognized in one of six OMHP group mice at 30 weeks.These results suggest that OMHP antigens play a role in the glomerular deposition of IgA and C3 in C3H/HeN mice. This is the first use of OMHP antigens to establish an active model of IgAN.

Immunoglobulin A nephropathy: a pathophysiology view

“…In several experimental studies, antigens capable of enhancing serum altered IgA1 or inducing IgAN have been tested, such as Staphylococcus aureus [62], H. influenzae [63], Sendai virus [64,65], gliadin [66]. On the other hand, no food or viral antigens were consistently found in mesangial deposits, suggesting a nonspecific alteration of IgA1 production via innate immune response [42].…”

Relationship between tonsils and IgA nephropathy as well as indications of tonsillectomy

“…Levels of IgA antibodies against H. parainfluenza outer membrane antigens were significantly increased in administration groups compared with controls. That is, administration of H. parainfluenza outer membrane antigens to mice may induce glomerular deposition of IgA and mesangial proliferation, resembling the changes seen in IgAN, with increases in IgA antibodies against H. parainfluenza outer membrane antigens [54]. Furthermore, production of cytokines IL-10 and transforming growth factor-b (TGFb) was enhanced by stimulation with H. parainfluenza outer membranes in tonsillar mononuclear cells from IgAN [55].…”

Prospects and Perspectives on IgA Nephropathy from Animal Models

“…The proclivity for mucosal immunization to drive IgA production led first to oral and subsequently nasal vaccination of mice [5,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] and rats [39][40][41][42][43][44][45][46][47] as a means to induce active models of IgAN. Inert proteins or infectious pathogens or their products served as antigens.…”

“…or by immunomodulation of extramucosal responses. Modulators include mucosal boosting with antigen [33, 38, 48], superantigens [36, 47, 49, 85] or stimuli of innate immunity [31,32,34,49,68]. Genetic or transgenic proclivity to dysregulation of B cells by T cells [50][51][52]75] and induced alterations in T cell cytokine profiles [33,38,77] are also recognized.…”