For the elucidation of a possible immunopathogenesis that leads to morphological and functional renal injury induced by alcohol abuse immunopathologic and ultrastructural studies were carried out on animal models; male Sprague-Dawley rats were
fed
a
regular diet with 3ml of 40% and 4ml of 10% alcohol for 3 days to 12 weeks. The control group animals were fed a regular diet with 3ml of normal saline daily instead of alcohol. The experimental animals were sacrificed on the 3rd 5th and 7th day,
4th,
8th and 12th week. The kidney, liver and small intestine were examined by light and electron microscopy, and the kidney and small intestine were also examined by immunofluorescence microscopy. No pathologic findings were observed by light
microscopy in
25 alcoholic and 6 control kidney samples. In one out of four rats after 8 weeks and three out of four rats after 12 weeks of 40% alcohol ingestion the IgA nephrogathy (IgAN) with dominant mesangial IgA deposits on immunofluorescence microscopy
and
mesangial electron dense deposits on electron microscopy were observed. These IgAN cases also showed weak depositions of IgM, IgG and C3. Albuminuria (3+) and proteinuria (300mg/dl) were found in a rat with IgAN of 40% alcohol ingestion for 12
weeks. In
the rest of the alcoholic rats up to 8 weeks of 40% alcohol ingestion and 12 weeks of 10% alcohol ingestion no immunoglobulin deposition was observed but mild abuminuria (+1) and urinary protein 30 mg/dl to 100 mg/dl were found in two of these
animals.
In this experimental study of animal models, chronic alcohol ingestion is clearly linked to renal disease even in the absence of liver cirrhosis. In alcoholic rats the mucosa of the small intestine revealed short and blunt villi with sloughing
off
of
the surface epithelial cells and an increased infiltration of plasma cells in the lamina propria. It is assumed that the mucosal inflammation may result in disturbances of the intestinal immune barrier and then promotes abnormal absorption of
macromolecules which stimulate plasma cells in the lamina propria to produce IgA. The small intestine of rats given 40% alcohol for 8 weeks stained with PITC Goat Anti-rat IgA revealed an increased number of IgA positive cells, presumable plasma
cells,
in the lamina propria compared to that of the 10% alcohol group or the control rats on immunofluorescence microscopy. This fact suggests that an increased number of plasma cells pathologically responded to an abnormal alimentary antigen by the
defense
mechanism system and clearly participated in an excessive production and secretion of IgA. These excessively produced IgA are combined with antigen of alimentary origin and produce IgA containing immune complexes which enter directly into the
circulation resulting an elevated IgA immune complex in the blood. There will be more IgA present in the liver; depending on the capacity of the liver to sequester or clear this increased supply, and elevated IgA immune complex levels occur in
the
circulation. In this study the liver revealed only a mild fatty change, which may render the saturation of Kupffer cells but there is no evidence of impairment in the clearing function according to an ultrastructural base. In the clearance of
IgA-containing immune complexes, the mononuclear phagocye system is important and an alcohol induced impaired hepatic immune complex clearance system might also contribute to an IgA increase. Therefore, the initiative point of the pathogenesis of
the
alcohol induced IgAN is an alimentary antigen, abnormally absorbed by altered intestinal mucosa induced by alcohol. The first step is a pathological response of plasma cells to the antigen enhancing synthesis of polymeric IgA which are combined
with the
antigen of alimentary origin and produce IgA containing immune complex. The second step is that these excessively produced IgA immune complexes enter directly into the circulation resulting in an elevated serum IgA immune complex which is
eventually8
deposited in the mesangium of glomeruli. On the basis of this experimental study, it can be postulated that alcohol induced IgAN explained by the mechanism of a possible immune complex-mediated disease.
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