Page 158 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

134 J. Charles Jennette, Ronald J. Falk and Adil. H. M. Gasim

Organ limited expressions of AAV occur, for example isolated cutaneous vasculitis, lung
capillaritis, upper respiratory tract granulomatosis, or pauci-immune necrotizing and
crescentic glomerulonephritis also called renal-limited vasculitis. In some but not all patients,
multisystem involvement is identified later. Isolated granulomatosis often is considered a
limited form of GPA and isolated vasculitis as a limited form of MPA if the lesions otherwise
are identical to those observed in systemic AAV.

Immune Complex Small Vessel Vasculitis

CHCC 2012 [1] defines immune complex SVV as vasculitis with moderate to marked
vessel wall deposits of immunoglobulin and/or complement components predominantly
affecting small vessels such as capillaries, venules, arterioles and small arteries;
glomerulonephritis is frequent.

Immune complex SVV differs immunopathologically from AAV with respect to the
extent of immunoglobulin deposited in vessel walls. This most likely is a reflection of the
different etiologies and pathogenic mechanisms. Immune complex vasculitis appears to result
from initial extensive localization of immune complexes in vessel walls followed by
complement activation and mediation of inflammation. The immunoglobulin is diffusely
distributed in the walls of affected small vessels. In contrast, AAV appears to be mediated by
more direct interaction of ANCA with neutrophils and monocytes resulting in activation that
in turn releases factors that activate the alternative complement pathway, which amplifies the
inflammation to cause the severe necrotizing lesions of AAV [13].

There are many forms of immune complex SVV caused by immune complexes of
different compositions. The antigens in pathogenic immune complexes can be derived from
heterologous sources such as infectious pathogens or drugs, and those from endogenous
sources such as autoantigens. CHCC 2012 only defines several of these many variants: anti-
glomerular basement membrane (anti-GBM) disease, CV, IgAV, and hypocomplementemic
urticarial vasculitis (HUV) (anti-C1q).

Anti-GBM disease is defined as vasculitis affecting glomerular capillaries, pulmonary
capillaries, or both, with basement membrane deposition of anti-basement membrane
autoantibodies. Lung involvement causes pulmonary hemorrhage, and renal involvement
causes glomerulonephritis with necrosis and crescents.

From an immunopathologic perspective, anti-GBM disease is somewhat distinct from
many other forms of immune complex vasculitis and glomerulonephritis because
immunostaining of involved capillaries shows linear staining rather than granular staining
(Figure 5). This is because the target autoantigen is a diffusely distributed constituent
component of the glomerular and alveolar capillary basement membranes, type IV collagen.
Thus, immune complexes containing anti-GBM antibodies and type IV collagen form in situ
diffusely along these basement membranes resulting in the linear staining. By contrast, other
type of immune complexes gather stochastically and irregularly within vessels walls
producing the granular pattern of immunostaining. The inflammatory vascular injury of anti-
GBM disease affects glomerular capillaries, pulmonary capillaries, or both, with focal rupture
of capillary walls and hemorrhage into the urinary space or alveolar air spaces.

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