Autoimmune Nephropathies

Pathology

Autoimmune nephropathies involve complex interactions between the immune system and renal tissues. In diseases like Systemic Lupus Erythematosus (SLE), autoantibodies bind to self-antigens, forming immune complexes which triggers the complement cascade and causes tissue damage and glomerulonephritis.  In diseases like Anti-Glomerular Basement Membrane (GBM) Disease, autoantibodies specifically target components of the glomerular basement membrane, leading to direct injury, and also activating complement and Fc receptors on immune cells, leading to localized inflammation and damage to the basement membrane. In IgA Nephropathy (Berger's Disease), there is defective glycosylation of IgA molecules, leading to the formation of abnormal IgA1 and form immune complexes. These immune complexes deposit in the mesangial region of the glomeruli, causing local inflammation and glomerular injury.

Diagnosis

1. Urinalysis
Proteinuria and Hematuria: Common in various autoimmune nephropathies, including SLE and IgA nephropathy.

2. Renal Biopsy
Commonly performed using imaging guidance to obtain a small tissue sample from the kidney for histopathological analysis:

SLE: Biopsy often shows immune complex deposition and glomerular inflammation.
IgA Nephropathy: Renal biopsy shows mesangial IgA deposits and abnormal IgA glycosylation patterns.
Anti-GBM Disease: Shows crescentic glomerulonephritis with GBM damage.
Vasculitis-Associated Nephropathies: Renal biopsy shows inflammatory infiltrates.

3. Autoantibody detection

• Anti-PLA2R antibodies
  Phospholipase A2 receptor (PLA2R) autoantibodies are highly specific for the primary form of MN.  PLA2R antibody titers decline in the course of spontaneous remission and during successful therapy. In addition to differential diagnosis of MN, the ELISA-based quantification of PLA2R autoantibodies allows assessment of disease activity and severity as well as prediction of disease outcome (remission, relapse) and risk of recurrence of MN after kidney transplantation.
• Anti-THSD7A Antibodies
  THSD7A was discovered as a second antigenic target in approx.
  2.5 % to 5 % of patients with idiopathic MN. As PLA2R, THSD7A is an N-glycosylated high molecular mass protein expressed on the podocyte membrane and similar to PLA2R antibodies, an association between THSD7A antibody levels and disease activity is suggested.
• Anti-Glomerular Basement Membrane (GBM) Antibodies
  Autoantibodies to GBM are highly specific and sensitive markers for Goodpasture's syndrome.The relevant antigenic target is the non-collagenous 1 (NC1) domain of the alpha-3 chain of type IV collagen within the GBM. High titers usually occur in patients with rapidly progressive kidney disease, and indicate an unfavourable prognosis.
• Anti-Neutrophil Cytoplasmic Antibodies (ANCA)
  Serological determination of ANCA is an essential tool for the identification and differentiation of ANCA-associated vasculitis (AAV). The most important ANCA target either proteinase 3 (PR3) which are sensitive and specific markers for Wegener's granulomatosis, or MPO which occur in microscopic polyangiitis and the Churg Strauss syndrome. The consensus on ANCA testing requires screening with indirect immunofluorescence (IIF) and confirmation in MPO- and PR3-ANCA specific assays.
• Anti-Nucleosome Antibodies (ANuA)
  ANuA represent the first serological marker described in SLE and are particularly suitable as a prognostic indicator for SLE with renal involvement: in lupus nephritis patients requiring transplantation a considerably high prevalence (79%) was observed compared to less severe cases (18%) and SLE patients without nephritis (9%).
• Anti-dsDNA Antibodies
  Anti-dsDNA is found in about 30% of people with systemic lupus and high levels of anti-dsDNA antibodies often suggests severe lupus, and kidney involvement (lupus nephritis). When the disease is active, especially in the kidneys, high amounts of anti-DNA antibodies are usually present. They can be used to monitor disease flare-ups and responses to therapy.