Quiz for ANCA

Though ANCA by description are antibodies directed against specific antigens in the cytoplasm of neutrophils some of the antigens like PR3 are present in monocytes. PR3 is a 29-kDa serine protease present in granules of neutrophils and monocytes. It is expressed on the surface of primed or apoptotic human neutrophils.

References–

• Wiik A. Rational use of ANCA in the diagnosis of vasculitis. Rheumatology (Oxford). 2002;41(5):481-483.
• Guchelaar NAD, Waling MM, Adhin AA, van Daele PLA, Schreurs MWJ, Rombach SM. The value of anti-neutrophil cytoplasmic antibodies (ANCA) testing for the diagnosis of ANCA-associated vasculitis, a systematic review and meta-analysis. Autoimmun Rev. 2021;20(1):102716.
• Bioactive proteinase 3 on the cell surface of human neutrophils: quantification, catalytic activity, and susceptibility to inhibition.Campbell EJ, Campbell MA, Owen CA J Immunol. 2000 Sep 15; 165(6):3366-74.

Explaination- C-ANCA are monospecific to PR 3. It is often recommended to follow-up If with PR 3 specific ELISA assay

References–
1) Wiik A. Rational use of ANCA in the diagnosis of vasculitis. Rheumatology (Oxford). 2002;41(5):481-483.

Perinuclear anti-neutrophilic cytoplasmic antibodies (P-ANCA) pattern may be seen to heterogeneous antigens, including myeloperoxidase (MPO), lactoferrin, elastase, cathepsin-G and bactericidal/permeability-increasing protein. The P-ANCA is seen in condition other than vasculitis like IBD, atrophic gastritis etc. c-ANCA, diffuse granular cytoplasmic staining with internuclear accentuation and p-ANCA homogeneous perinuclear staining with nuclear extension occurs due to the relocation of negatively charged cytoplasmic autoantigens to the nuclear membrane upon alcohol fixation.

References–
1) Wiik A. Rational use of ANCA in the diagnosis of vasculitis. Rheumatology (Oxford). 2002;41(5):481-483
2) Argyropoulou OD, Goules AV, Boutzios G, Tsirogianni A, Sfontouris C, Manoussakis MN, Vlachoyiannopoulos PG, Tzioufas AG, Kapsogeorgou EK. Occurrence and Antigenic Specificity of Perinuclear Anti-Neutrophil Cytoplasmic Antibodies (P-ANCA) in Systemic Autoimmune Diseases. Cells. 2021 Aug 19;10(8):2128. doi: 10.3390/cells10082128. PMID: 34440897; PMCID: PMC8393570.
3) Johannes Schulte-Pelkum, Antonella Radice, Gary L. Norman, Marcos Lόpez Hoyos, Gabriella Lakos, Carol Buchner, Lucile Musset, Makoto Miyara, Laura Stinton, Michael Mahler, "Novel Clinical and Diagnostic Aspects of Antineutrophil Cytoplasmic Antibodies", Journal of Immunology Research, vol. 2014, Article ID 185416, 12 pages, 2014. https://doi.org/10.1155/2014/185416
4) Lin MW, Silvestrini RA, Culican S, Campbell D, Fulcher DA. A dual-fixed neutrophil substrate improves interpretation of antineutrophil cytoplasmic antibodies by indirect immunofluorescence. Am J Clin Pathol. 2014 Sep;142(3):325-30. doi: 10.1309/AJCPG02FGQVAUSIU. PMID: 25125622.

Reason- all of them ( GPA, MPA, and eGPA )are classified as ANCA-associated vasculitis (AAV) and are positive for ANCA screening test.

Reference-
1) Guchelaar NAD, Waling MM, Adhin AA, van Daele PLA, Schreurs MWJ, Rombach SM. The value of anti-neutrophil cytoplasmic antibodies (ANCA) testing for the diagnosis of ANCA-associated vasculitis, a systematic review and meta-analysis. Autoimmun Rev. 2021;20(1):102716