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Observational Study
. 2020 May 1;59(5):979-987.
doi: 10.1093/rheumatology/kez348.

Elevated free secretory component in early rheumatoid arthritis and prior to arthritis development in patients at increased risk

Klara Martinsson  1 , Karin Roos Ljungberg  1 , Michael Ziegelasch  1 , Jan Cedergren  1 , Per Eriksson  1 , Vladimir Klimovich  2 , Åsa Reckner  1 , Irina Griazeva  2 , Christopher Sjöwall  1 , Marina Samoylovich  2 , Thomas Skogh  1 , Jonas Wetterö  1 , Alf Kastbom  1
Affiliations
Observational Study

Elevated free secretory component in early rheumatoid arthritis and prior to arthritis development in patients at increased risk

Klara Martinsson et al. Rheumatology (Oxford). .

Abstract

Objectives: Considering growing evidence of mucosal involvement in RA induction, this study investigated circulating free secretory component (SC) in patients with either recent-onset RA or with ACPA and musculoskeletal pain.

Methods: Two prospective cohorts were studied: TIRA-2 comprising 452 recent-onset RA patients with 3 years of clinical and radiological follow-up, and TIRx patients (n = 104) with ACPA IgG and musculoskeletal pain followed for 290 weeks (median). Blood donors and three different chronic inflammatory diseases served as controls. Free SC was analysed by sandwich ELISA.

Results: Serum levels of free SC were significantly higher in TIRA-2 patients compared with TIRx and all control groups (P < 0.01). Among TIRx patients who subsequently developed arthritis, free SC levels were higher compared with all control groups (P < 0.05) except ankylosing spondylitis (P = 0.74). In TIRA-2, patients with ACPA had higher baseline levels of free SC compared with ACPA negative patients (P < 0.001). Free SC status at baseline did not predict radiographic joint damage or disease activity over time. In TIRx, elevated free SC at baseline trendwise associated with arthritis development during follow-up (P = 0.066) but this disappeared when adjusting for confounders (P = 0.72). Cigarette smoking was associated with higher levels of free SC in both cohorts.

Conclusion: Serum free SC levels are increased in recent-onset RA compared with other inflammatory diseases, and associate with ACPA and smoking. Free SC is elevated before arthritis development among ACPA positive patients with musculoskeletal pain, but does not predict arthritis development. These findings support mucosal engagement in RA development.

Keywords: clinical progress; cyclic citrullinated peptide antibodies (ACPA); free secretory component; musculoskeletal pain; rheumatoid arthritis (RA).

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Figures

<sc>Fig</sc>. 1
Fig. 1
Serum free SC in recent-onset RA (TIRA-2), ACPA-positive patients with musculoskeletal pain (TIRx) and controls Control groups comprise SLE, AAV, AS and healthy blood donors. Bars denote mean (red) and s.d. (black). Comparisons between the different groups (analysed using Mann–Whitney test) with corresponding P-values are displayed in the inset table. AAV: ANCA-associated vasculitis; SC: secretory component.
<sc>Fig</sc>. 2
Fig. 2
Serum free SC in relation to ACPA IgG and smoking (A) Serum levels of free SC according to ACPA IgG status among patients with recent-onset RA (TIRA-2). (B) Free SC levels according to smoking status in TIRA-2 and ACPA-positive patients with musculoskeletal pain (TIRx). Differences were tested by Mann–Whitney test. Bars denote mean (red) and s.d. (black). SC: secretory component.
<sc>Fig</sc>. 3
Fig. 3
Correlations between baseline levels of free SC and different ACPAs Correlation test between free SC and SC-ACPA (A), ACPA IgM (B), ACPA IgA (C) and ACPA IgG (D) in recent-onset RA (TIRA-2). Correlation statistics were obtained from Spearman tests. SC: secretory component; SC-ACPA: SC-containing ACPA.
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