Antineutrophil cytoplasmic antibodies and associated diseases: A review of the clinical and laboratory features

Abstract

There have been a number of recent advances in this field. First, the "International Consensus Statement on Testing and Reporting of Antineutrophil Cytoplasmic Antibodies (ANCA)" has been developed to optimize ANCA testing. It requires that all sera are tested by indirect immunofluorescent (IIF) examination of normal peripheral blood neutrophils and, where there is positive fluorescence, in enzyme-linked immunosorbent assays (ELISAs) for antibodies against both proteinase 3 (PR3) and myeloperoxidase (MPO). Testing will be further improved when international standards and common ELISA units are available. Second, new diagnostic criteria for the small vessel vasculitides that take into account ANCA-positivity and target antigen specificity as well as histologic features are currently being produced. Third, we understand that the complications associated with treatment of the ANCA-associated vasculitides are often more hazardous than the underlying disease, and regimens that use effective but less toxic agents are being evaluated. The factors associated with increased risk of relapse, however, remain incompletely understood. Finally, ANCA with specificities other than PR3 and MPO are present in many nonvasculitic autoimmune diseases. Their clinical significance is still largely unclear, and some of the target antigens are present in other cells as well as neutrophils and thus are not strictly "ANCA."

Antibodies to selected minor target antigens in patients with anti-neutrophil cytoplasmic antibodies (ANCA)

“…As seen in this study and others [25], some patients WG or with microscopic polyangiitis -up to 40% in some reports, particularly patients with 'limited' WG [26] -do not have antibodies to either PR3 or MPO. In IF + sera that do not contain PR3-or MPO-ANCA, there is a greater frequency of antibodies to minor antigens than in sera that contain PR3-or MPO-ANCA.…”

Antineutrophil Cytoplasmic Autoantibody in the Absence of Wegener's Granulomatosis or Microscopic Polyangiitis: Implications for the Surgical Pathologist

“…P-ANCA can be seen in various connective tissue diseases, such as in rheumatoid arthritis, inflammatory arthritis, progressive systemic sclerosis, and other disorders (4,33,38,84). In rheumatoid arthritis, granulocyte-specific ANA can closely resemble P-ANCA in IIF tests (3,5,38,82). Finally, novel or uncharacterized antibodies could conceivably give rise to ANCA.…”

“…For example, a small focus of vasculitis or capillaritis could be overlooked when another pattern predominates. Although many hospital laboratories only perform IIF testing, it is highly recommended that a positive ANCA result be followed by an ELISA for PR-3 and/or myeloperoxidase (3,5,11,14,33,82,83,86,88). The pathologist should inquire as to what type of ANCA test was performed (IIF versus ELISA), where it was performed (hospital versus reference versus research laboratory), and whether multiple autoantibodies (antinuclear antibodies, rheumatoid factor, antiglomerular basement membrane (79) Anticytokeratins (80) antibody, or others) are present.…”

“…The pulmonary diseases that are most frequently associated with ANCA include Wegener's granulomatosis (WG), microscopic polyangiitis (MPA), Churg Strauss syndrome, and other disorders (2)(3)(4)(5). Elevated ANCA titers particularly occur during disease exacerbation but may be low or absent in remission (3,6,7).…”

“…In MPA, ANCA are present in Յ80% of sera, and the staining pattern tends to be perinuclear (P-ANCA; 4). ELISA assays in P-ANCAϩ sera detect myeloperoxidase but occasionally identify other antigens (2)(3)(4)(5)11).…”