Levels of Rheumatoid Factor May Mark Two Distinct Types of EGPA, Study Says

Levels of rheumatoid factor — an antibody against healthy tissue found in some autoimmune diseases — appear to separate eosinophilic granulomatosis with polyangiitis (EGPA) patients into two subtypes with different disease mechanisms, a study suggests.

“Subtypes in eosinophilic granulomatosis with polyangiitis classified according to rheumatoid factor” was published in the journal Clinical Rheumatology.

While rheumatoid factor is an autoantibody primarily characteristic of rheumatoid arthritis, as many as 45% of EGPA patients are positive for it as well, suggesting a role in the disease.

To investigate this, researchers at Keio University School of Medicine, in Tokyo, reviewed the clinical data of 16 EGPA patients diagnosed at their hospital between August 1998 and February 2019.

Patients were divided in two groups according to the median levels of rheumatoid factor: those with levels below the median (75 IU/ml), and those with levels higher or equal to the median. Then, clinical features were compared between these groups.

People with low factor levels, they found, were positive for ANCA antibodies against the myeloperoxidase (MPO) protein, had mild higher counts of eosinophils — the type of white blood cell that causes EGPA, and tended to have more frequent heart and kidney involvement, although this difference was not significant.

Those with high rheumatoid factor levels were negative for MPO-ANCA antibodies, had an extreme increase in eosinophil counts, and more frequently had disease symptoms in their musculoskeletal and gastrointestinal systems as well as skin lesions. Gastrointestinal symptoms, in particular, were seen in 60% of these people, and in no patient with low levels.

The researchers suggested that the high eosinophil levels and negative MPO-ANCA levels seen in patients in the high rheumatoid factor group may be the result of increased levels of interleukin (IL)-5, a signaling protein that controls the development, proliferation, and growth of eosinophils.

A previous Phase 3 trial (NCT02020889) of a therapy targeting IL-5 in patients with EGPA showed that those who began the study with high eosinophil level responded better to the treatment. Future research should examine whether rheumatoid factor levels can predict the effectiveness of the IL-5 inhibitor.

This study’s findings show that “patients with EGPA can be separated into two groups according to RF [rheumatoid factor] with distinct clinical and laboratory characteristics,” the researchers wrote.

Results suggest that the mechanisms underlying EGPA may be different in these groups, possibly implying a need for different treatment strategies.