3. IgA Nephropathy (Berger Disease)
• Characterized by the presence of prominent
IgA deposits in the
mesangial
regions, detected by immunofluorescence
microscopy.
4. IgA Nephropathy
• The disease can be suspected by light
microscopic examination, but
the diagnosis is made only
by immunocytochemical
techniques
5. IgA Nephropathy
• The disease can be suspected by light
microscopic examination, but
the diagnosis is made only
by immunocytochemical
techniques
6.
7. IgA Nephropathy
• Whereas IgA nephropathy is typically an
isolated renal disease, similar IgA deposits
are present in a systemic disorder of
children, Henoch-Schönlein purpura which
has many overlapping features with IgA
nephropathy. In addition, secondary IgA
nephropathy occurs in patients with liver and
intestinal diseases.
8. Pathogenesis
• IgA, the main Ig in mucosal secretions, is
present in plasma at low concentrations,
mostly in monomeric form,
the polymeric forms
being catabolized in
the liver.
9. Pathogenesis
• In IgA nephropathy, plasma polymeric IgA is
increased, and circulating IgA-
containing immune complexes
are present in some patients.
10. IgA Nephropathy
It is clear that increased production of IgA
cannot itself cause this disease. Although
there are two subclasses of IgA molecules in
humans (IgA1 and IgA2), Only IgA1
forms the nephritogenic deposits of IgA
nephropathy.
11. IgA Nephropathy (Berger Disease)
Pathogenesis
• The prominent mesangial deposition of IgA
suggests entrapment of IgA immune
complexes in the mesangium, and the
presence of C3 combined with the absence of
C1q and C4 in glomeruli points to activation
of the alternative complement pathway and
initiate glomerular injury. .
12. IgA Nephropathy (Berger Disease)
• A genetic influence is suggested by the
occurrence of this condition in families and
in HLA-identical brothers and the increased
frequency of certain HLA and complement
genotypes in some populations.
13. Pathogenesis
• A genetic or acquired abnormality of
immune regulation leading to
increased IgA synthesis in response
to respiratory or gastrointestinal exposure to
environmental agents (e.g., viruses, bacteria,
food proteins).
14. Pathogenesis
• IgA1 and IgA1-containing
immune complexes are then
trapped in the mesangium,
where they activate the
alternative complement
pathway and initiate glomerular
injury.
15. Pathogenesis- Secondary IgA nephropathy
• IgA nephropathy occurs with increased
frequency in individuals with gluten
enteropathy (celiac disease), in whom
intestinal mucosal defects are well defined,
and in liver disease, in which there is
defective hepatobiliary clearance of IgA
complexes (secondary IgA nephropathy).
16. Pathogenesis
• Alternatively, there is evidence for
qualitative alterations in the IgA1
molecule itself, specifically a defect in
normal galactosylation that makes it
immunogenic, giving rise to autoantibodies
against the IgA1 that form immune
complexes that deposit in the mesangium.
17. Morphology
On histologic examination the lesions vary considerably.
1.The glomeruli may be normal or may show
2. mesangial widening and endocapillary
proliferation (mesangioproliferative
glomerulonephritis),
3.segmental proliferation confined to some
glomeruli (focal proliferative glomerulonephritis),
4. or rarely, overt crescentic glomerulonephritis.
5.The presence of leukocytes within glomerular
capillaries is a variable feature.
19. Morphology- Immunofluorescence
• The characteristic immunofluorescent picture
is of mesangial deposition of IgA,
often with C3 and properdin and
lesser amounts of IgG or IgM.
• Early complement components are usually
absent.
20.
21. Clinical Features
The disease affects people of any age, but older
children and young adults are most commonly
affected.
Many patients present with gross hematuria
after an infection of the respiratory
or, less commonly, gastrointestinal
or urinary tract.
22. Clinical Features
• 30% to 40% have only microscopic
hematuria, with or without proteinuria; and
5% to 10% develop a typical
acute nephritic
syndrome.
23. Clinical Features
• The hematuria typically lasts for
several days and then subsides,
only to return every few months.
The subsequent course is highly variable.
24. Clinical Features
• Many patients maintain normal renal
function for decades. Slow progression to
chronic renal failure
occurs in 15% to 40% of cases over a
period of 20 years.
25. Clinical Features
• Onset in old age, heavy proteinuria,
hypertension, and the extent of
glomerulosclerosis on biopsy are clues to an
increased risk of progression.
• Recurrence of IgA deposits in transplanted
kidneys is frequent.
26. Clinical Features
• In approximately 15% of those with recurrent
IgA deposits, there is resulting clinical
disease, which most frequently runs the
same slowly progressive course as that of the
primary IgA nephropathy.
