Antipeptidyl Arginine Deiminase Type 4 Antibodies Show No Clinical Utility in RA

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Antipeptidyl arginine deiminase type 4 antibodies have no current clinical utility in rheumatoid arthritis.

Antipeptidyl arginine deiminase type 4 antibodies (anti-PAD4) have no current clinical utility in rheumatoid arthritis (RA), especially when compared with anti-citrullinated protein antibodies (ACPA), according to results published in the Journal of Rheumatology.

The study included participants with RA (n=745). The researchers used the DELFIA technique to identify serum immunoglobulin G antibodies to human recombinant PAD4 and also performed genotyping of the PADI4 gene using Taqman assays in 945 patients with RA and 1118 controls.

The researchers detected anti-PAD4 antibodies in 26% (n=193) of participants. Of participants with anti-PAD4 antibodies, 77% (n=149) were also positive for ACPA.

Differences between anti-PAD4-positive and anti-PAD4-negative participants were seen in female sex (82.9% vs 75.9%, P =.04), patients with a history of smoking (54.3% vs 66.6%; P =.004), rheumatoid factor positivity (64.0% vs 49.9%; P =.001), and ACPA positivity (77.2% vs 57.4%; P =1.0×10-6).

The results did not indicate any association between anti-PAD4 status and clinical characteristics, PADI4 polymorphisms, or genetic risk scores after stratification for ACPA status, which suggests that ACPA status may influence patient characteristics.

In ACPA-positive participants, the percentage of patients with a history of smoking was lower in anti-PAD4-positive participants compared with anti-PAD4-negative participants (54.5% vs 69.0%, P =.004). This difference was not seen in ACPA-negative participants.

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“The lack of association between anti-PAD4, clinical characteristics, and genetic risk factors suggests that anti-PAD4 is not a primary driver of the RA pathogenesis,” the researchers wrote.

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Guderud K, Mæhlen MT, Nordang GBN, et al. Lack of association among peptidyl arginine deiminase type 4 autoantibodies PADI4 polymorphisms, and clinical characteristics in rheumatoid arthritis [published online June 1, 2018]. J Rheumatol. doi:10.3899/jrheum.170769