2. Introduction
• The most common GN globally
• Described in the late 1960s by Berger and Hinglais
• Characterized by : deposition predominantly of IgA (and, to a
lesser extent, of other immunoglobulins) in the mesangium
with mesangial proliferation
3. Introduction
• Clinical features : span from asymptomatic hematuria to
rapidly progressive glomerulonephritis
• 40% of patients may progress to ESRD
• Idiopathic form
• Associated with a variety of disease processes
4. Introduction
• Age : all ages, most common in the second and third decades
of life, uncommon below 10 yrs of age
• Sex : M > F ( 2:1 to 6:1 )
5. Classification
• Primary IgAN
• Secondary IgAN
o Infections : Toxoplasmosis , HIV , Leprosy
o Rheumatological : Seronegative RA , Ankylosing spondylitis ,
Reiter’s syndrome
o GIT : Celiac disease , Dermatitis herpetiformis , Crohn’s
disease , Liver disease , Alcoholic cirrhosis
6. o Neoplasia : Mycosis fungoides , Lung carcinoma , Mucin-
secreting carcinoma
o Hematological : Cyclic neutropenia , ITP
o Eye : Scleritis , Sicca syndrome
o HSP
o Pulmonary hemosiderosis
• Familial IgA Nephropathy
8. IgA
• Most produced antibody overall, but has lower serum
concentrations. Released into secretions (tears, saliva, mucus) and
breast milk.
• Mucosal defense.
• Monomer (in circulation) or dimer (with J chain when secreted).
• It has two subclasses, IgA1 and IgA2.
9. IgA
• Mucosal antigen challenge provokes polymeric IgA (pIgA) production by
plasma cells of the mucosa-associated lymphoid tissue.
• Crosses epithelial cells by transcytosis. Picks up secretory component from
epithelial cells, which protects the Fc portion from luminal proteases---
released as secretory IgA (sIgA).
• The function of circulating IgA is less clear . It is bone marrow derived and
mostly monomeric IgA1 (mIgA1) and is cleared from the circulation by the
liver .
10. Pathogenesis
• Susceptibility to IgAN and risk of disease progression :
influenced by a confluence of genetic and environmental
factors.
• Multi-“hit” process
• Central finding : presence of circulating and glomerular
immune complexes comprised of galactose-deficient IgA1, an
IgG autoantibody directed against the hinge region O-glycans,
and C3.
11. Pathogenesis
• Immune complexes : nephritogenic, contributing directly to
glomerular inflammation and mesangial proliferation.
• Activation of the local and systemic RAAS and complement
activation : glomerulosclerosis and tubulo-interstitial fibrosis,
leading to loss of renal function.
• Coexistent risk factors such as hypertension and smoking
contribute to disease progression, potentially through
microvascular injury .
12. Familial IgAN
• Familial IgA nephropathy has been reported in multiple ethnic
groups around the world, including in Africa and Central
America.
• Some studies suggest that 4% to 14% of patients with IgA
nephropathy may have a family history of renal disease.
• Inheritance : Autosomal dominant transmission with
incomplete penetrance .
13. Characteristics of Pathogenic IgA
• Abnormal mucosal antigen handling.
o pIgA1 production is downregulated in the mucosa and upregulated
in the bone marrow.
• Poor 0-glycosylation of IgA1
o Increased tendency to both self-aggregate and form antigen-
antibody complexes with IgG antibodies directed against an N-
acetylgalactosamine residue in the IgA1 hinge region.
• Impaired systemic clearance of IgA by liver
16. • Asymptomatic microscopic hematuria with/out proteinuria :
30% to 40%
• Hematuria with HTN : IgA nephropathy is the most common
cause
• Intermittent macroscopic hematuria occurs in 25% of these
patients.
17. Presentations
IgAN may have any presentation
o Hematuria (macroscopic / microscopic ) with/out HTN
o AKI
o RPGN
o Nephrotic syndrome
o ESRD
18. Favourable prognostic markers
• The proliferative forms of IgAN seem to be associated with
better outcomes in children than in adults.
• Patients with episodes of gross (macroscopic) hematuria
generally have a more favorable prognosis than those with
persisting microhematuria
20. Immunofluorescence Microscopy
• Prominent, globular deposits of IgA (often accompanied by
C3 and IgG) in the mesangium and, to a lesser degree, along
the glomerular capillary wall.
• This deposited IgA is predominantly J chain containing
polymeric IgA1.
21.
22. Light Microscopy
• Mesangial proliferation and matrix expansion : diffuse > focal
• Focal segmental or global glomerular sclerosis : disease has
been ongoing for some time.
• Segmental crescents : relatively common, although they may
be missed by sampling error if only a few glomeruli are
obtained
23.
24. Electron Microscopy
• Electron-dense deposits : primarily limited to the mesangium
but may also occur in the subendothelial and subepithelial
spaces.
