High-Titer Rheumatoid Factor, Anticitrullinated Peptide Antibody May Increase Risk for Poor Outcomes

Researchers evaluated the effect of the level of rheumatoid factor and/or anticitrullinated peptide antibody positivity titer on disease activity, functional status, and treatment strategy in rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) with high-titer rheumatoid factor (RF) and/or anticitrullinated peptide antibody (ACPA) may be at increased risk for poor outcomes, according to study results published in The Egyptian Rheumatologist.

Researchers assessed the effect of the level of RF or ACPA positivity titer on the disease activity, functional status, and treatment strategy among patients with RA.

This cross-sectional study included a total of 120 participants (87.5% women; mean age 46.9±10.9 years) with RA who attended the rheumatology outpatient clinic at Cairo University Hospitals. All participants had available autoantibody information and fulfilled American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) 2010 criteria. Seropositivity results indicated that 49.2% (n=49) had high positive ACPA or RF titers, 36.7% (n=44) had low titers, and 14.2% (n=17) had negative titers. Patients with negative titers were excluded from the study.

Participants were grouped by the following level of ACPA or RF positivity: group 1 contained individuals with low ACPA or RF positivity, and group 2 contained individuals with high titers. Assessments were based on disease activity score using 28 joint counts (DAS28) and modified health assessment questionnaire (MHAQ); the Mann-Whitney test was used to compare variables.

Individuals in the high-titer group had significantly higher global assessment of disease activity compared with the low-titer group (6.1±2.1 vs 5.2±1.8, respectively; P =.04), as well as higher subcutaneous nodules (25±42.4 vs 10±22.7, respectively; P =.037) and MHAQ score (7.6±4.6 vs 6±3.4, respectively; P =.058). Both the current (5 [median, 0-5] vs 0 [0-5]; P =.006) and cumulative (2.74 [0.24-18.25] vs 0.5 [0.14-5.02]; P =.012) steroid doses were significantly higher among those in the high-titer group compared with the low-titer group, respectively.

Limitations to this study include the absence of radiological data and the combination of both RF and ACPA participants into a single group.

The study researchers concluded, “[H]igh-titer RF and/or ACPA may contribute to poor outcome[s] in RA as with other factors including the presence of subcutaneous nodules, impaired functional status, as well as the need for higher daily and cumulative steroid doses as an indirect indicator of increased disease activity and, in turn, poor outcome[s].”


Sobhy N, Ghoniem SA, Eissa BM, Kamal A, Medhat A, Elsaid NY. Disease characteristics in high versus low titers of rheumatoid factor or anti-citrullinated peptide antibody in rheumatoid arthritis patients. Published online May 10, 2022. Egypt Rheumatol. doi: 10.1016/j.ejr.2022.04.004