Granulomatous Inflammation in ANCA-Associated Vasculitis

TY - JOUR

T1 - Granulomatous Inflammation in ANCA-Associated Vasculitis

AU - Müller, Antje

AU - Krause, Bettina

AU - Kerstein-Stähle, Anja

AU - Comdühr, Sara

AU - Klapa, Sebastian

AU - Ullrich, Sebastian

AU - Holl-Ulrich, Konstanze

AU - Lamprecht, Peter

PY - 2021/6/17

Y1 - 2021/6/17

N2 - ANCA-associated vasculitis (AAV) comprises granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). While systemic vasculitis is a hallmark of all AAV, GPA is characterized by extravascular granulomatous inflammation, preferentially affecting the respiratory tract. The mechanisms underlying the emergence of neutrophilic microabscesses; the appearance of multinucleated giant cells; and subsequent granuloma formation, finally leading to scarred or destroyed tissue in GPA, are still incompletely understood. This review summarizes findings describing the presence and function of molecules and cells contributing to granulomatous inflammation in the respiratory tract and to renal inflammation observed in GPA. In addition, factors affecting or promoting the development of granulomatous inflammation such as microbial infections, the nasal microbiome, and the release of damage-associated molecular patterns (DAMP) are discussed. Further, on the basis of numerous results, we argue that, in situ, various ways of exposure linked with a high number of infiltrating proteinase 3 (PR3)- and myeloperoxidase (MPO)-expressing leukocytes lower the threshold for the presentation of an altered PR3 and possibly also of MPO, provoking the local development of ANCA autoimmune responses, aided by the formation of ectopic lymphoid structures. Although extravascular granulomatous inflammation is unique to GPA, similar molecular and cellular patterns can be found in both the respiratory tract and kidney tissue of GPA and MPA patients; for example, the antimicrobial peptide LL37, CD163+ macrophages, or regulatory T cells. Therefore, we postulate that granulomatous inflammation in GPA or PR3-AAV is intertwined with autoimmune and destructive mechanisms also seen at other sites.

AB - ANCA-associated vasculitis (AAV) comprises granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). While systemic vasculitis is a hallmark of all AAV, GPA is characterized by extravascular granulomatous inflammation, preferentially affecting the respiratory tract. The mechanisms underlying the emergence of neutrophilic microabscesses; the appearance of multinucleated giant cells; and subsequent granuloma formation, finally leading to scarred or destroyed tissue in GPA, are still incompletely understood. This review summarizes findings describing the presence and function of molecules and cells contributing to granulomatous inflammation in the respiratory tract and to renal inflammation observed in GPA. In addition, factors affecting or promoting the development of granulomatous inflammation such as microbial infections, the nasal microbiome, and the release of damage-associated molecular patterns (DAMP) are discussed. Further, on the basis of numerous results, we argue that, in situ, various ways of exposure linked with a high number of infiltrating proteinase 3 (PR3)- and myeloperoxidase (MPO)-expressing leukocytes lower the threshold for the presentation of an altered PR3 and possibly also of MPO, provoking the local development of ANCA autoimmune responses, aided by the formation of ectopic lymphoid structures. Although extravascular granulomatous inflammation is unique to GPA, similar molecular and cellular patterns can be found in both the respiratory tract and kidney tissue of GPA and MPA patients; for example, the antimicrobial peptide LL37, CD163+ macrophages, or regulatory T cells. Therefore, we postulate that granulomatous inflammation in GPA or PR3-AAV is intertwined with autoimmune and destructive mechanisms also seen at other sites.

KW - Animals

KW - Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis

KW - Antibodies, Antineutrophil Cytoplasmic/immunology

KW - Autoimmune Diseases/diagnosis

KW - Autoimmunity

KW - Biomarkers

KW - Cell Movement/immunology

KW - Disease Management

KW - Disease Susceptibility

KW - Granulomatosis with Polyangiitis/diagnosis

KW - Humans

KW - Immunity, Innate

KW - Immunohistochemistry/methods

KW - Organ Specificity/immunology

U2 - 10.3390/ijms22126474

DO - 10.3390/ijms22126474

M3 - SCORING: Review article

C2 - 34204207

VL - 22

JO - INT J MOL SCI

JF - INT J MOL SCI

SN - 1661-6596

IS - 12

M1 - 6474

ER -