glomerulopathies –iga nephropathy iga nephropathy - pathogenesis

Glomerulopathies –IgA nephropathy

IgA nephropathy - Pathogenesis



Mesangial IgA promotes glomerular inflammation a series of events ……. can cause end stage renal disease



What specific mechanisms influence the deposition of IgA and its initiation of inflammation?



tightly T cell controlled processes

in health most polymeric IgA

is produced in the mucosal immune system

is involved in mucosal defense

the bone marrow produces monomeric IgA, which reaches the circulation



in IgA nephropathy synthesis of polymeric IgA is increased in the bone marrow

and decreased in the mucosa



Yes it is



Why might this happen? This process is very tightly T cell regulated

In response to a mucosal antigen, T cells reach the circulation, but will return to the mucosa to synthesize polymeric IgA if they express alpha 4 beta 7, the mucosal homing receptor

If on the other hand, a systemic antigen is confronted, T cells will home to the marrow if they express the alpha 4 beta 1 systemic homing receptor



in IgA nephropathy - these processes is abnormal

there is an exaggeration of systemic homing receptor expression, which would drive T cells not back to the mucosa but towards the marrow the abnormal site of IgA1 production, which is one of the features of IgA nephropathy



in IgA nephropathy - these processes is abnormal but not only

there is an exaggeration of systemic homing receptor expression, which would drive T cells not back to the mucosa but towards the marrow the abnormal site of IgA1 production, which is one of the features of IgA nephropathy

structural abnormalities of the IgA molecule itself



Abnormal IgA1 molecule

promote IgA1 self-aggregation production of macromolecular IgA1

act as an antigen production of IgA1-IgG complexes, which could be deposited

influence interaction directly with matrix components and particularly with mesangial cells


IgA nephropathy - a great clinical heterogeneity


IgA nephropathy is often presenting

as recurrent visible hematuria

coinciding with mucosal infection

which is almost never seen over the age of 40


IgA nephropathy

a few patients will present nephrotic proteinuria


IgA nephropathy

other patients will be picked up because they have an asymptomatic urine abnormality


IgA nephropathy

others will already have advanced kidney disease when they’re first picked up


“Is this one disease?

Is this the same disease we’re picking up at different stages?”

Prof J. Feehally Dept of NephrologyLeicester General Hospital Leicester, United Kingdom


IgA nephropathy

in a global view of this disease it’s extremely different in its prevalence


IgA nephropathy

also a very variable prognosis


IgA nephropathy - prognosis

proteinuria, hypertension and GFR at the time of diagnosis predict outcome

that’s true for any glomerular disease


IgA nephropathy – prognosis

glomerulosclerosis, interstitial fibrosis, tubular atrophy predict outcome

that’s true for any glomerular disease



proteinuria you have not just at presentation but during prolonged follow up is a very powerful predictor of outcome

!!



how much proteinuria you have during follow up combined with mean arterial pressure during follow up are the most powerful predictor of outcome


IgA nephropathy and Henoch Schonlein Purpura



What is IgA nephropathy? characterised by predominant mesangial IgA deposits by

immunofluorescence on the renal biopsy

there is no clinical nor serological features, which are specific for IgA nephropathies

to make the diagnosis, you really need a renal biopsy with appropriate immunofluorescence

What is Henoch Schonlein Purpura? a true clinical syndrome

characterised by palpable purpura, arthritis, and abdominal pain, and of course, a glomerulonephritis characterised by predominant IgA deposits



a more accurate definition of H.S.Purpura

a small vessel vasculitis with IgA dominant deposits involving skin, gut, and glomeruli associated with arthritis



IgA deposits in the mesangium –for sure it is a primary IgA nephropathy or a H.S.Purpura

rule out a systemic disease associated with IgA deposits



a typical picture of IgA deposits

characterized by granular mesangial deposits of IgA



A more aggressive type of IgA nephropathy associated with much more massive immunoglobulin deposits of IgA there is thorough extension of IgA deposits along the capillary wallsis usually associated with proliferative lesion and endocapillary proliferation



C3 is also found in the mesangium generally with a more or less identical

pattern than for IgA – generally the intensity is a little bit weaker



A more aggressive case - massive deposits of C3 in mesangial area, and

also extension along the capillary walls



H.S.Purpura is generally a more aggressive type of

glomerulonephritis than IgA nephropathy


management recommendations



There is no specific treatments for this condition

Glomerulopathies

glomerulopathies –iga nephropathy iga nephropathy - pathogenesis

Documents

iga molecule

monomeric iga

deposition of iga

mucosa slide

circulation slide

nephrotic proteinuria

systemic homing receptor

end stage renal disease