Anti-gingipain antibodies and ACE1 activity in rheumatoid arthritis: associations with disease activity and cardiovascular comorbidity in a cross-sectional study.
Kaminska M, Chrobak M, et al. • Rheumatology international • 2026
In a cross-sectional study of 177 RA patients and 147 healthy controls, PAD4-potentiating activity, anti-gingipain antibodies, and ACE1 activities did not differ between groups overall, though exploratory within-RA signals emerged: anti-Kgp levels were weakly associated with disease activity and therapy, and lower ACE1 activity was associated with synthetic DMARDs use.
Key Findings
Results
PAD4-potentiating activity, anti-Kgp, anti-RgpB, and ACE1 activities did not differ significantly between RA patients and healthy controls.
177 RA patients and 147 healthy controls were included in the study.
Clinical profiling included DAS28, CRP/ESR, treatments, and comorbidities.
PAD4-potentiating activity, ACE1 activities, and anti-gingipain antibodies were measured using standardized in-house assays.
Between-group differences were described as 'limited overall.'
Results
Anti-Kgp antibody levels showed a weak but statistically significant positive correlation with DAS28 disease activity scores in RA patients.
The correlation was characterized as 'weak' by the authors.
This association did not remain significant in covariate-adjusted models.
None of the biomarkers showed independent associations with DAS28 in adjusted models.
Results
Anti-Kgp antibody levels were lower in RA patients using biologic disease-modifying antirheumatic drugs (bDMARDs).
Lower anti-Kgp was observed among biologic DMARD users compared to non-users.
This represented one of two key exploratory within-RA signals identified.
The authors suggest anti-Kgp may reflect a 'mucosal-immune axis' relevant to comorbidity patterns.
The finding was not pre-specified and requires prospective validation.
Results
ACE1 enzymatic activity was lower among RA patients using synthetic DMARDs across all three substrates tested.
Lower ACE1 activity was observed across all three substrates in synthetic DMARD users.
Statistical significance was reported as 'all pā0.01ā0.04'.
This represented the second key exploratory within-RA signal identified.
The authors suggest ACE1 activity may reflect a 'vascular-remodeling axis' potentially related to comorbidity patterns.
Results
Discrimination for cardio-metabolic outcomes using the studied biomarkers was limited in the overall RA cohort.
ROC analyses were used to explore discrimination for selected comorbidities.
Overall discrimination for cardio-metabolic outcomes was described as 'limited.'
Small, predefined strata showed 'exploratory signals,' but low event counts and multiple comparisons constrain inference.
The authors specifically note that 'low event counts and multiple comparisons constrain inference.'
Discussion
The authors propose that anti-Kgp and ACE1 (N-domain) together may reflect mucosal-immune and vascular-remodeling axes that could relate to comorbidity patterns in RA.
Anti-Kgp is an antibody against Porphyromonas gingivalis gingipain Kgp, a periodontal pathogen implicated in RA pathogenesis.
ACE1 N-domain activity was specifically highlighted as potentially relevant.
The authors call for 'prospective, pre-specified validation' of these signals.
The study design was cross-sectional, limiting causal inference.
What This Means
This research examined whether three types of blood markers ā antibodies against a gum disease bacterium (Porphyromonas gingivalis), an enzyme involved in blood pressure regulation (ACE1), and an activity that can modify proteins in ways linked to rheumatoid arthritis (PAD4-potentiating activity) ā were different in people with rheumatoid arthritis (RA) compared to healthy individuals, and whether these markers related to disease severity or heart and metabolic health problems. The study included 177 people with RA and 147 healthy controls in a cross-sectional design, meaning everyone was measured at one point in time.
Overall, the three markers did not differ significantly between RA patients and healthy controls. However, within the RA group, two smaller patterns emerged: patients with higher levels of anti-Kgp antibodies (against the gum disease bacterium) tended to have slightly higher disease activity scores, and patients taking biologic medications had lower anti-Kgp levels. Additionally, patients taking conventional synthetic disease-modifying drugs had lower ACE1 enzyme activity. These findings were described as exploratory and weak, and did not hold up when other factors were statistically accounted for. The ability of these markers to identify which RA patients had heart or metabolic problems was also limited.
This research suggests that antibodies to a gum disease bacterium and a blood vessel-related enzyme may be connected to disease activity and treatment responses in RA, but the connections are subtle and not yet strong enough to be clinically useful. The authors emphasize that these are preliminary signals that need to be confirmed in larger, prospectively designed studies before any firm conclusions can be drawn about their role in RA management or cardiovascular risk assessment.
Kaminska M, Chrobak M, Silva L, de Oliveira Y, Bielecka E, Pinto A, et al.. (2026). Anti-gingipain antibodies and ACE1 activity in rheumatoid arthritis: associations with disease activity and cardiovascular comorbidity in a cross-sectional study.. Rheumatology international. https://doi.org/10.1007/s00296-026-06272-4