IgA NEPHROPATHY

Lecture 44

IgA nephropathyIgA nephritisBerger's disease,

Berger's syndrome

Synpharyngitic glomerulonephritis

IgA Nephropathy (Berger Disease)

• Characterized by the presence of prominent

IgA deposits in the

mesangial regions, detected by immunofluorescence microscopy.

IgA Nephropathy• The disease can be suspected by light

microscopic examination, but

the diagnosis is made only by immunocytochemical techniques

IgA Nephropathy• The disease can be suspected by light

microscopic examination, but

the diagnosis is made only by immunocytochemical techniques

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.

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.

Pathogenesis• In IgA nephropathy, plasma polymeric IgA is

increased, and circulating IgA-containing immune complexes are present in some patients.

IgA NephropathyIt 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.

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. .

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.

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).

Pathogenesis

• IgA1 and IgA1-containing immune complexes are then trapped in the mesangium, where they activate the alternative complement pathway and initiate glomerular injury.

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).

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.

MorphologyOn histologic examination the lesions vary considerably.

1.The glomeruli may be normal or may show2. 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.

LM• Mesangial Proliferation

•Matrix increase

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.

Clinical FeaturesThe 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.

Clinical Features

• 30% to 40% have only microscopic hematuria, with or without proteinuria; and 5% to 10% develop a typical

acute nephritic syndrome.

Clinical Features

• The hematuria typically lasts for several days and then subsides, only to return every few months. The subsequent course is highly variable.

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.

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.

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.