Background/Purpose: Identification of seropositive individuals at risk for arthritis development would open opportunities for early clinical intervention. In a recent study on seropositive arthalgia patients (SAP), 35% of the patients were found to develop RA within 12 months (van de Stadt et al, Ann Rheum Dis 2012). Not only autoantibodies precede clinically apparent synovitis but also serological immune features are modulated prior to the development of clinical synovitis (Rantapää-Dahlquist et al, Ann Rheum Dis 2007). So far, little is known on modulation of leukocyte subsets before arthritis development. Therefore, in a cross sectional study, we investigated and compared the numbers of circulating leukocyte subsets and levels of cytokines, cytokine receptors, chemokines in SAP,  new-onset RA and in long-standing RA patients.

Methods: Whole blood samples obtained from 32 patients with arthralgia who were ACPA and/or RF-positive (termed seropositive arthralgia patients [SAP]), 50 early RA (39 were ACPA+ and/or RF+, 11 were ACPA- and RF-), 11 long-standing RA patients (all were ACPA+ and/or RF+) and 33 healthy controls (HC) were used to quantify the absolute numbers of leukocyte populations. Serum samples from 20 HC, 30 SAP, 21 early ACPA/RF+, 11 early ACPA/RF- RA and 8 long-standing RA patients were used to quantify systemic levels of cytokines, cytokine receptors and chemokines using Human Cytokine 25-plex Panel.

Results: Seropositive arthralgia patients showed a decrease of both the absolute number and the frequency of NK-cells compared to HC (p=0.006 and p=0.004, respectively). A similar decrease of NK-cell absolute number and frequency was observed for ACPA/RF+ early RA patients (p=0.004 and p=0.018, respectively) but not for ACPA/RF- early RA patients. The majority of systemic cytokines/cytokine receptors (IL-1β, IL-1RA, IL-2R, TNF-α, IFN-α, IL-4, IL-17, IL-2, IL-15, GM-CSF) and chemokines (MIP-1β, IL-8, Rantes, Eotaxin, MCP-1, MIP-1α, MIG)  were found to be elevated both in SAP and in early ACPA/RF+ RA compared to HC, while the levels found in ACPA/RF- RA patients were similar to HC.

Conclusion: Seropositive arthralgia patients, showed decreased numbers of circulating NK-cells and upregulation of various mediators of systemic inflammation. The same was found in ACPA/RF-positive early RA but not in ACPA/RF- negative early RA. Immune alterations found in SAP and early RA seem to be related to the presence of ACPA and or RF. In addition, marked differences in leukocytes and inflammatory markers between autoantibody- positive and –negative early RA patients suggest clear differences in disease pathogenesis between these groups.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/decreased-nk-cell-numbers-and-upregulation-of-markers-of-systemic-inflammation-in-autoantibody-positive-arthralgia-patients-and-early-rheumatoid-arthritis-patients-but-not-in-autoantibody-neg/