NEW YORK, New York—The anti-inflammatory effect of TNFα inhibitors used in rheumatoid arthritis (RA) treatment occur partly because these drugs restore the balance of activating and inhibitory immunoglobulin G (IgG) receptors on neutrophils and suppress activation of these cells when they encounter immune complexes, according to researchers from Weill Medical College of Cornell University in New York.

“We hypothesized that TNFα blockade in RA might alter the relative expression of activating and inhibitory FcR and thereby decrease inflammation.”—Kristina Belostocki, MD.
Investigators led by Kristina Belostocki, MD, reported in Arthritis & Rheumatism that infliximab (INF) treatment shifted >50% of RA patients’ neutrophil receptor profiles away from those associated with amplifying immune-complex-induced activation and toward those that inhibit such activation.1 The effect persisted over at least 3 months of treatment.

“The induction of inhibitory FcγRIIb was always associated with decreased levels of [activating] FCγRIIa, and improvement following INF therapy, as measured using the Health Assessment Questionnaire (HAQ), was significantly associated with down-regulation of FCγRIIa,” Dr. Belostocki said. The researchers used fluorescence-activated cell sorting and Western blotting to examine receptor expression on neutrophils in 24 patients with RA both before their first infusion of INF and immediately before ≥3 subsequent infusions. Expression of the activating IgG receptor decreased in 13 of 24 patients (54.2%) after INF treatment.

“We hypothesized that TNFα blockade in RA might alter the relative expression of activating and inhibitory FcR and thereby decrease inflammation,” Dr. Belostocki said. What’s more, the researchers suspect that shifting the balance of activating and inhibitory FcγR might raise the threshold for neutrophil activation.

“The correlation of the HAQ score with the balance of FcγRII isotype expression suggests that the effects of TNFα blockade on FcγRII isotype expression have clinical implications,” the authors wrote. They note that more studies are needed to clarify the role of these receptors in response to RA treatment.

J. W. J. Bijlsma, MD, chair of the department of rheumatology and clinical Immunology at University Medical Center in Utrecht, The Netherlands, agreed telling Musculoskeletal Report, “We believe that indeed the balance between stimulatory and inhibiting factors, including Fc, play a role. This is probably not TNFα-specific but more related to effective decrease in disease activity.”

Dr. Bijlsma also noted that many mechanisms are involved in the pathophysiology of RA, and that “perhaps at one moment in time some pathways are more prominent than at another moment in time [in the same patient].”

Reference
1. Belostocki K, Pricop L, Redecha PB, et al. Infliximab treatment shifts the balance between stimulatory and inhibitory Fcγ receptor type II isoforms on neutrophils in patients with rheumatoid arthritis. Arthritis Rheum. 2008;58:384-388.