Distinct ANCA Autoantibodies Predict Different Organ Involvement, Outcomes in AAV, Study Shows

Classifying the specificity of ANCA autoantibodies may complement the currently used clinical classification system when predicting the course of disease and prognosis in ANCA-associated vasculitis (AAV) patients with renal involvement, according to Spanish researchers.

Indeed, ANCA specificity was seen to be better at predicting relapse than clinical classification.

Patients with ANCA antibodies targeting the proteinase 3 protein are twice as likely to relapse than those with myeloperoxidase (MPO)-ANCA, researchers found.

The study, “Determinants of renal and patient outcomes in a Spanish cohort of patients with ANCA-associated vasculitis and renal involvement,” was published in the journal Clinical Rheumatology.

The prognosis of ANCA-associated vasculitis is difficult to determine due to the many organs and body systems affected by the disease.

Though AAV can be classified, normally according to the International Chapel Hill Consensus Conference (CHCC) Nomenclature of Systemic Vasculitides, it’s still uncertain which classification gives the more accurate prognosis.

Some researchers have proposed a different system, based on the type of ANCA autoantibodies produced by the patient.

There are usually one of two types of autoantibodies in AAV patients: one that targets myeloperoxidase (MPO-ANCA) or one that targets proteinase 3 (PR3-ANCA).

Studies showed that ANCA autoantibodies are better at predicting relapses in patients from northern Europe and the U.S., a population who predominantly carries PR3-ANCA.

Researchers in Spain aimed to determine the differences in patient outcomes between MPO-ANCA and PR3-ANCA serotypes in the Spanish population.

They looked at whether ANCA autoantibodies are a better predictor of relapses in Spanish patients, who, unlike AAV patients in northern Europe and the U.S., have a higher prevalence of MPO-ANCA.

Researchers compared kidney progression, relapses, and survival among three AAV classification systems: the ANCA serotype, histopathological — based on lesions detected in kidney biopsies, and the Chapel Hill nomenclature – which identifies disease subtypes.

These include granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA).

In total, 245 patients with AAV and kidney involvement diagnosed from 2000 to 2014 were recruited from several Spanish nephrology services. They were followed-up by a median of 43.2 months.

Overall, this was the largest group of patients with MPO and PR3-ANCA with kidney involvement reported in Spain so far.

A majority of patients, 82%, had an MPO-ANCA type, while only 18% were PR3-ANCA positive, which correlates with other southern European, Asian, and Pacific populations.

In total, 82.9% of patients exhibited microscopic polyangiitis (MPA) and 17.1% had granulomatosis with polyangiitis (GPA).

This also correlates with previous knowledge that MPO-ANCA is preferentially associated with MPA and PR3-ANCA associated with GPA.

Researchers could not find a significant association between ANCA types or clinical classification with renal outcome and patients’ survival.

There were no differences in serum creatinine or proteinuria levels, markers of kidney impairment, between PR3-ANCA or MPO-ANCA patients at diagnosis.

However, histopathological exams of biopsies were able to predict renal outcome, defined as the probability of developing end-stage renal disease (ESRD), a life-threatening condition.

Patients with lesions classified as sclerotic, crescentic, and mixed were at higher risk of ESRD than those within the focal category.

Importantly, the team found that ANCA serotype was a strong predictor of relapse. Patients carrying PR3-ANCA relapsed twice as often as patients with MPO-ANCA.

Also, PR3-AAV and MPO-AAV had different organ involvement and kidney lesions.

Crescentic kidney lesions were more frequent in patients with PR3-ANCA, suggesting these have more active lesions.

Those who were PR3-ANCA-positive were younger, more often male, and had more widespread organ involvement, particularly the respiratory tract, and had more frequent joint pain, fever, and coughing up of blood.

The involvement of the gastrointestinal (GI) tract was found to be a risk factor for relapses, which had never been reported before.

However, neither clinical distinction between MPA and GPA or a histopathological examination of kidney biopsies were capable of predicting relapses.

There were no significant differences between PR3-ANCA and MPO-ANCA groups regarding Rituxan (rituximab) and plasma exchange treatment, time to start induction treatment, or duration of induction treatment.

The study demonstrated PR3-ANCA serotype is a strong predictor of relapses. And PR3-ANCA and MPO-ANCA serotypes have different widespread organ involvement and different kidney lesions.

“A classification based on ANCA specificity has a higher predictive value for relapse occurrence,” researchers wrote in the study.

“The categorization of patients by ANCA serotype should be used to choose the induction treatment and the duration of maintenance therapy,” they added.