Page 680 - Textbook of Pathology, 6th Edition

664 membranous GN. The examples of planted non-glomerular deposits, reflecting activation of alternate pathway of
antigens are cationic proteins, lectins, DNA, bacterial products complement. Such patients have circulating anti-comple-
(e.g. a protein of group A streptococci), viral and parasitic mentary nephritic factor (C3NeF) which is an IgG antibody
products and drugs. and acts as an autoantibody to the alternate C3 convertase,
ii) Circulating immune complex deposits. This mechanism leading to persistent alternate pathway activation.
used to be considered very important for glomerular injury The deposits in alternate pathway disease are charac-
but now it is believed that circulating immune complexes teristically electron-dense under electron microscopy;
cause glomerular damage under certain circumstances only. glomerular lesions in such cases are referred to as dense-
These situations are: their presence in high concentrations deposit disease.
for prolonged periods, or when they possess special Alternate pathway disease occurs in most cases of type
properties that cause their binding to glomeruli, or when host II membranoproliferative GN, some patients of rapidly
mechanisms are defective and fail to eliminate immune progressive GN, acute diffuse proliferative GN, IgA
complexes. The antigens evoking antibody response may be nephropathy and in SLE.
endogenous (e.g. in SLE) or may be exogenous (e.g. Hepatitis 4. OTHER MECHANISMS OF ANTIBODY-MEDIATED
B virus, Treponema pallidum, Plasmodium falciparum and INJURY. A few autoantibodies have been implicated in some
various tumour antigens). The antigen-antibody complexes patients of focal segmental glomerulosclerosis and few other
are formed in the circulation and then trapped in the types of GN. These antibodies include the following:
glomeruli where they produce glomerular injury after i) Anti-neutrophil cytoplasmic antibodies (ANCA). About
combining with complement. 40% cases of rapidly progressive GN are deficient in
Immune complex GN is observed in the following human
diseases: immunoglobulins in glomeruli (pauciimmune GN) and are
positive for ANCA against neutrophil cytoplasmic antigens
i) Primary GN e.g. acute diffuse proliferative GN, memb- in their circulation. ANCA causes endothelial injury by
ranous GN, membranoproliferative GN, IgA nephropathy generation of reactive oxygen radicals. ANCA-mediated
and some cases of rapidly progressive GN and focal GN. vasculitis is also seen in Wegenger’s granulomatosis and
ii) Systemic diseases e.g. glomerular disease in SLE, malaria, Churg-Strauss syndrome.
syphilis, hepatitis, Henoch-Schonlein purpura and idiopathic
mixed cryoglobulinaemia. ii) Anti-endothelial cell antibodies (AECA). Auto-
antibodies against endothelial antigens have been detected
2. ANTI-GBM DISEASE. Less than 5% cases of human GN in circulation in several inflammatory vasculitis and
SECTION III
are associated with anti-GBM antibodies. The constituent of glomerulonephritis. These antibodies increase the
GBM acting as antigen appears to be a component of collagen adhesiveness of leucocytes to endothelial cells.
IV of the basement membrane. The experimental model of
anti-GBM disease is Masugi nephritis (nephrotoxic serum B. Cell-mediated Glomerular Injury
nephritis) produced in rats by injection of heterologous (Delayed-type Hypersensitivity)
antibodies against GBM prepared in rabbits by immunisation
with rat kidney glomerular tissue. There is evidence to suggest that cell-mediated immune
Anti-GBM disease is classically characterised by reactions may be involved in causing glomerular injury,
interrupted linear deposits of anti-GBM antibodies (mostly IgG; particularly in cases with deficient immunoglobulins (e.g.
rarely IgA and IgM) and complement (mainly C3) along the in pauci-immune type glomerulonephritis in RPGN).
glomerular basement membrane. These deposits are detected Cytokines and other mediators released by activated T cells
Systemic Pathology
by immunofluorescence microscopy or by electron stimulate cytotoxicity, recruitment of more leucocytes and
microscopy. fibrogenesis. CD4+ T lymphocytes recruit more macrophages
Anti-GBM disease is characteristically exemplified by while CD8+ cytotoxic T lymphocytes and natural killer cells
glomerular injury in Goodpasture’s syndrome in some cases cause further glomerular cell injury by antibody-dependent
of rapidly progressive GN. About half to two-third of the cell toxicity. Soluble factor derived from T lymphocytes is
patients with renal lesions in Goodpasture’s syndrome have implicated in proteinuria in minimal change disease and focal
pulmonary haemorrhage mediated by cross-reacting GS.
autoantibodies against alveolar basement membrane (page However, cell-mediated injury is yet less clear than
494). antibody-mediated glomerular injury.
3. ALTERNATE PATHWAY DISEASE. As apparent from C. Secondary Pathogenetic Mechanisms
the above mechanisms, the complement system, in (Mediators of Immunologic Injury)
particular C3, contributes to glomerular injury in most
forms of GN. Deposits of C3 are associated with the early Secondary pathogenetic mechanisms are a number of
components C1, C2 and C4 which are evidence of classic mediators of immunologic glomerular injury operating in
pathway activation of complement. But in alternate man and in experimental models. These include the
pathway activation, there is decreased serum C3 level, following:
decreased serum levels of factor B and properdin, normal 1. NEUTROPHILS. Neutrophils are conspicuous in certain
serum levels of C1, C2 and C4 but C3 and properdin are forms of glomerular disease such as in acute diffuse prolife-
found deposited in the glomeruli without immunoglobulin rative GN, and may also be present in membranoproliferative