Complement Defects

Appreciate the role of complement mediated diseases in this classification of etiology of RPGN
Also, appreciate Alternate Pathway vs Classic Pathway mediated diseases among complement mediated disease
Also, appreciate, not all immune complex mediated disease will have complement activation

Causes of RPGN
    • a) Anti - GBM 
    • b) ANCA Vasculitis 
    • c) Immune complex disease 
      • Low Complement Immune Complex Disease 
        • Alternate Pathway (Normal C4, Depressed C3; decreased Factor B)
          • Usually uncommon in clinical medicine
          • Pediatric renal diseases MPGN, C3 Glomerulopathies, 
          • IgG 2 and IgG 4 do not activate classic pathways, and upon binding to protein can activate alternate pathway. This can sometime happen in SLE
          • Also involved during or by Dialysis, some microbes,
          • aHUS

        • Classic Pathway (Depressed C4, Normal or Low C3)
      • Normal Complement Immune Complex Diseases
        • Ig A Nephropathy IgA Nephropathy NEJM 2013
        • HSP (Henoch-Scholein Purpura)
        • Fibrillary GN (Polyclonal Gammopathy), Immunotactoid GN (Monoclonal Gammopathy) 
This is an example of cryoglobuminemia as an example of complement mediated disease.