Background and Objectives Joint-draining lymph nodes (LN) and afferent lymphatics are relevant components of the induction-resolution phases of immune responses, acting through the control of cell efflux from the joint and regulation of peripheral inflammation. LN reactivity to exogenous stimuli associates with morphological and vascular flow dynamic changes. While the dynamics of draining LN have been extensively investigated in infectious and neoplastic diseases, much remains to be understood regarding their involvement in human autoimmune conditions.
In this study, we have developed of a non-invasive power Doppler ultrasound (PDUS) system for the assessment of human axillary LN blood flow characteristics and investigated its significance in relationship with disease activity and outcome in rheumatoid arthritis (RA).
Materials and Methods 101 subjects were recruited in the study: 20 healthy volunteers, 33 RA patients with active disease candidate to biologic therapy and 48 RA patients in stable clinical remission candidate to drug-free follow-up. All patients underwent complete clinical-laboratory evaluations and joint-axillary LN PDUS assessments. LN were evaluated for volume (by ellipsoid formula), cortex hypertrophy and vascular flow distribution. All evaluations were performed at baseline and at 6 months after biologic treatment initiation, and every 3 months following DMARD suspension.
Results Vascular flow characteristics were assessed semi-quantitatively according to the degree of PD distribution in LN cortex (0-1 PD signals/2-3/4-5 /≥6). Validation assessments showed good inter-rater agreement (k = 0.86) and strong correlation between the score and overall PD+vascular signal defined by digital image analysis (rho = 0.9, p<0.01). A grading system referring to the maximum observed score was adopted to define a patient-related index. In subjects with detectable LN, the LN PD grade significantly discriminated active RA from controls. RA patients in remission revealed a trend towards reduction in the prevalence of high PD grades compared to active RA, but not a systematic return to normalcy. In active RA a significant correlation was observed between LN PD grade and joint PD score (p<0.05), but not with DAS28, SJC28, TJC28, ESR, CRP. Pilot prospective evaluations following biologic treatment pointed at the axillary LN PD grade as the only predictor of DAS28 remission at 6 months (OR 2.53, 95% CI 1,21-5,31, p = 0.01).
Conclusions Non-invasive vascular flow assessment by PDUS of axillary LN seems a feasible, reliable and valid tool to capture clinically-relevant changes of draining LN status. This may be important to better focus invasive procedures for biological studies and as a novel approach for biomarker discovery in RA.