Autoimmune Diseases

Review Article

Pathophysiological Relationship between Infections and Systemic Vasculitis

Table 2

Theories regarding the role of infection in the development of primary systemic vasculitis. Toll-like receptor (TLR); 3 proteinase (PR3); myeloperoxidase (MPO).


Vasculitis	Mechanism	Microbial agent	Evidence	References

Takayasu’s arteritis	Molecular mimicry	Mycobacterium tuberculosis	Mycobacterium tuberculosis gene sequences IS6110 and HupB in tissues from aorta Increased T cell response to hHSP60 and mHSP65	[9, 10, 37]

MPO-AAV	Neutrophil cell traps	Various	Immunofluorescence analyses revealed MPO located in these extracellular chromatin fibers IgG ANCA induced neutrophil NETs In crescentic glomerulonephritis, lesion associated with AAV has detected NETs Increased levels of MPO-DNA complex in the serum Induced pauci-immune glomerulonephritis and alveolar hemorrhage in rats exposed to PTU/PMA	[38–40]

PR3-AAV	Neutrophil cell traps	Various	Immunofluorescence analyses revealed MPO located in these extracellular chromatin fibers Murine anti-PR3 antibody induced NETs	[38]
	Stimulation of T lymphocytes by S. aureus superantigen	S. aureus	Persistent activation of circulating T lymphocytes Chronic carriers of S. aureus that expressed toxic shock toxin 1 (TSS-1) had increased numbers of relapses	[27, 28, 36]
	Antigens can join to renal basement membranes by charge interaction	S. aureus	—	[41]
	Idiotype, anti-idiotype	S. aureus	Similarity of some bacterial peptides, including but not limited to S. aureus, with complementary PR3 (PR3c)	[42]
	TLR activation	S. aureus	During active infection of AAV, TLR9 expression increased significantly compared to uninfected patients Increased expression of TLR9 in monocytes from patients with AAV (S. aureus carriers) TLR2 and TLR9 were stimulated in vitro, and increased membrane expression of PR3 (PR3m) In patients with AAV-PR3, hypomethylated CpG motifs triggered production of PR3-ANCA by autoreactive LB	[43–45]
	Molecular mimicry	Klebsiella and Escherichia coli species	Anti-lysosomal-associated membrane protein-2 (hLAMP-2)	[46–49]