Atypical ANCAs Do Not Contribute to Vessel Inflammation in Patients with Eye Disease, Study Suggests

The presence of atypical ANCA antibodies in people with underlying eye inflammatory disease is not linked to severe vessel inflammation or worse outcomes, a small study reports.

The study, “Atypical Perinuclear Anti-Neutrophil Cytoplasmic Antibodies in Ocular Inflammatory Diseases,” was published in the journal Ocular Immunology and Inflammation.

ANCA-associated vasculitis is a kind of blood vessel inflammation caused by the production of excess ANCA antibodies. Most patients have antibodies against the proteinase-3 (PR3) or the myeloperoxidase (MPO) proteins, but other, atypical ANCAs have also been described.

While the role of anti-PR3 and anti-MPO autoantibodies is well-studied, there is little information on how atypical ANCA antibodies influence patients’ outcomes.

Therefore, researchers examined the clinical features of patients with ocular inflammatory diseases — which affect 16% of ANCA-associated vasculitis patients — who were positive for atypical ANCA antibodies.

Their study included 813 patients diagnosed with ocular inflammatory disease. Among them, 19 (2.3%) had PR3 antibodies, eight (1%) had MPO antibodies, and 34 (4.2%) had atypical ANCA antibodies. These were mostly women (68%) whose median age was 57.

Of the 34 patients with atypical ANCAs, 21 had uveitis, an inflammation of the middle layer of the eye, or uvea; seven had scleritis, inflammation of the white coating of the eye, or sclera; three had a form of autoimmune disease in the eye, and three had dry eye or conjunctivitis, an inflammation of the thin layer covering the white part of the eye.

The majority of the atypical ANCA patients had no severe forms of eye inflammation.

Scleritis was the most common disease associated with a systemic blood vessel inflammation. Three patients, all with scleritis, had some form of vasculitis, including one with microscopic polyangiitis and one with granulomatosis with polyangiitis. These conditions, however, were likely caused by the presence of common ANCA antibodies and not by atypical ANCAs.

The majority of the patients had a good prognosis, and only 3% developed disease exacerbations, all of which were treated with appropriate therapy.

Overall — and contrary to what is seen in patients with PR3 and MPO autoantibodies — atypical ANCAs are not associated with severe vessel inflammation or poorer prognosis.

“In contrast to other forms of ANCA, in the presented series atypical [ANCA] was associated with non-vasculitic diseases in most patients,” researchers concluded.