Immunoglobulin A vasculitis nephritis: Current understanding of pathogenesis and treatment

Table 1 Mechanism of immunoglobulin A vasculitis nephritis pathogenesis

No.	Mechanism of IgAVN pathogenesis
1	Infection triggers (Helicobacter pylori, Streptococcus pneumoniae and Haemophilus Influenzae[22-25]
2	Genetic factors[26-28]
3	Impaired glycosylation of IgA1 (Gd-IgA1)[29-41]
4	Complement activation[42-45]
5	TLR activation and B cell proliferation[46-48]
6	AECAs[49-51]
7	NAPIr[52,53]
8	Elevated plasma levels of IgE, eosinophil activation, higher levels of ECP and renal α-SMA[54-56]

IgAVN: Immunoglobulin A vasculitis nephritis; Gd-IgA1: Galactose-deficient-immunoglobulin A; TLR: Toll-like-receptor; AECAs: Anti-endothelial cell antibodies; NAPIr: Nephritis-associated plasmin receptor; α-SMA: α-smooth muscle; ECP: Eosinophil cationic protein.

Table 2 Treatments according to European treatment guidelines

		Class of drugs	Ref.
Mild IgAVN	First line	Corticosteroids: Oral prednisolone	[60-62]
	Second line (or corticosteroid-sparing agent)	Immunosuppressive therapies: Pulsed methylprednisolone or AZA or MMF, CsA	[6,71,72]
Moderate IgAVN	First line	Corticosteroids: Oral prednisolone and/or pulsed methylprednisolone	[6,60-62]
	Second line (Cortico-dependent and cortico-resistant forms of IgAVN)	Immunosuppressive therapies: AZA, MMF, CYC iv	[71,72]
Severe IgAVN	First line	Immunosoppresive therapies + corticosteroids: AZA or MMF or CYC, CNIs (Cyclosporin A or Tacrolimus), Rituximab, Plasmapheresis	[64-66,74-77]
New drugs: Dapsone, Narsoplimab, Sparsentan			[81,82]
RAS blockers (ACEIs and ARBs) should be used in IgAVN as soon as possible			[78-80]

ACEI: Angiotensin-converting enzyme inhibitors; ARBs: Angiotensin receptor blockers; IgAVN: Immunoglobulin A vasculitis nephritis; AZA: Azathioprine; MMF: Mycophenolate mofetil; CsA: Cyclosporine A; CYC: Cyclophosphamide; CNIs: Calcineurin inhibitors.