Anti-Neutrophil Cytoplasmic Antibodies in Generalized Autoimmune Diseases

Abstract

Anti-neutrophil cytoplasmic antibodies (ANCA) are a system of autoantibodies which are strongly associated with the primary systemic vasculitides (PSV). cANCA, as detected by indirect immunofluorescence, are mostly reactive to pro-teinase 3 (PR3) and bear high sensitivity and specificity for Wegener’s granulomatosis. pANCA have varied subspecificities and clinical associations. The most important subspecificity of pANCA is anti-myeloperoxidase (MPO), which is strongly associated with microscopic polyaniitis and pauci-immune crescentic glomerulonephritis. pANCA also occur at low to moderate frequency in other PSV, collagen vascular disease, inflammatory bowel disease and autoimmune liver disease. In systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), pANCA of varied subspecificity have been found, including anti-MPO at low rate and low titer, while cANCA and anti-PR3 were generally absent. Consequently, anti-PR3 (PR3-ANCA) and anti-MPO (MPO-ANCA) at moderate and high titer are distinguishing features of the PSV and, in an appropriate clinical setting, argue strongly against the presence of SLE or RA. Since no significant clinical association has been found for other pANCA subspecificities, cANCA, PR3-ANCA and MPO-ANCA remain the critical elements of ANCA testing in the clinical diagnosis of generalized autoimmune diseases.

Antineutrophil cytoplasmic antibodies in patients with systemic lupus erythematosus: prevalence, antigen specificity, and clinical associations

“…As detected by IIF technique using ethanol-and formaldehyde-®xed neutrophils as substrate, ANCA were present in 29.1% of SLE patients, a percentage similar to that found by Schnabel et al [9]. Almost all of the positive samples produced a P-ANCA staining pattern, while the cytoplasmic pattern was seen in only one serum.…”

“…On the other hand, ANA usually present in high titres, so they can``overshadow'' the more weakly positive ANCA. Additional testing on formaldehyde-®xed granulocytes is always necessary to dierentiate true P-ANCA from ANA [9]. However, some authors doubt the usefulness of IIF on formaldehyde-®xed neutrophils and do not recommend it for routine use because formalin-acetone ®xation leads to increased auto¯uores-cence, diculties in visualising weak positive reactions, and loss of antigen reactivity to autoantibodies [23].…”

“…It can also be found in connective tissue diseases such as systemic lupus erythematosus (SLE) [9], but this occurrence has not received the same attention as in primary systemic vasculitides due to the presence of a wide array of autoantibodies, some of which are closely associated with speci®c clinical manifestations and disease activity. Vasculitis and glomerulonephritis are characteristic manifestations of SLE, which frequently appears in the dierential diagnosis of primary systemic small vessel vasculitides.…”

Cytomegalovirus infection in systemic necrotizing vasculitis: causative agent or opportunistic infection?

“…The ®nding of anti-MPO-ANCA in the present patient may favor the diagnosis of idiopathic MPA rather than CMV-associated vasculitis. However, a decision based on the ®nding of anti-MPO-ANCA appears to be problematic because anti-MPO-ANCA have been found in diseases other than MPA, and up to 50% of patients with MPA are anti-MPO negative [7,8]. In the present case, the diagnosis of a CMV-associated vasculitis was considered on account of the detection of CMV-DNA by PCR.…”

Anca-Associated Glomerulonephritis: Relationship of Main Anca Subtypes to Renal Outcome, Age and Sex of the Patients

“…These antibodies are present in a large number of diseases. [9][10][11][12][13][14][15][16][17][18] Using IIF, which is the method of choice for ANCA detection, either of two major patterns can be seen-a cytoplasmic pattern (cANCA) or a perinuclear pattern (pANCA). The cANCA pattern is most often caused by anti-PR3, and in rare cases by anti-MPO.…”