Synovial features of patients with rheumatoid arthritis and psoriatic arthritis in clinical and ultrasound remission differ under anti-TNF therapy: a clue to interpret different chances of relapse after clinical remission?

Abstract

Objective: To define the synovial characteristics of patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in clinical and ultrasound remission achieved by combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockers.

Methods: Patients with RA in remission (n=25) (disease activity score (DAS)<1.6 for at least 6 months), patients with RA in low disease activity (LDA) (n=10) (1.6<DAS<2.4 for at least 6 months) and patients with PsA in remission (n=18) (DAS<1.6 and Psoriasis Area Severity Index (PASI)=0 for at least 6 months) achieved by MTX+anti-TNF (adalimumab 40 mg or etanercept 50 mg) with power Doppler (PDUS)-negative synovial hypertrophy underwent synovial tissue biopsy. Patients with RA with high/moderate disease naïve to treatment (n=50) were included as a comparison group. Immunostaining for cluster designation (CD)68, CD21, CD20, CD3, CD31 and collagen was performed.

Results: PDUS-negative patients with RA in remission showed lower histological scores for synovial CD68⁺, CD20⁺, CD3⁺ cells and CD31⁺ vessels and collagen deposition (p<0.05 for both lining and sublining) compared with PDUS-positive patients with RA with high/moderate disease. In addition, there was no significant difference in terms of lining and sublining CD68⁺, CD20⁺, CD3⁺, CD31⁺ cells and collagen comparing PDUS-negative patients with RA in remission and in LDA, respectively. On the contrary, PDUS-negative patients with PsA in remission showed higher histological scores for sublining CD68⁺ (p=0.02) and CD3⁺ cells (p=0.04) as well as CD31⁺ vessels (p<0.001) than PDUS-negative patients with RA in remission.

Conclusions: PDUS-negative patients with RA in remission have comparable synovial histological features than PDUS-negative patients with RA in LDA. However, patients with PsA in remission are characterised by a higher degree of residual synovial inflammation than patients with RA in remission, despite PDUS negativity under TNF inhibition.

Keywords: Anti-TNF; Psoriatic Arthritis; Rheumatoid Arthritis; Synovitis; Ultrasonography.

Figure 1

(A–I) IHC staining for CD68/CD21 and CD3/CD20 on ST of patients with rheumatoid arthritis (RA) in disease remission, in low disease activity (LDA) and in high/moderate disease. (A) Example photos of CD68 (red)/CD21 (brown) (A^{a, b}) and CD3 (red)/CD20 (brown) (A^c,d) staining of ST biopsies from patients with RA with high/moderate disease activity naïve to any DMARDs treatment (magnification 20×). (B) Example photos of CD68 (red)/CD21 (brown) (B^{a, b}) and CD3 (red)/CD20 (brown) (B^c,d) staining of ST biopsies from patients with RA in LDA status (magnification 20×). (C) Example photos of CD68 (red)/CD21 (brown) (C^{a, b}) and CD3 (red)/CD20 (brown) (C^c,d) staining of ST biopsies from patients with RA in clinical remission (magnification 20×); ultrasound assessment (US) picture with power doppler (PD) scale of the knee used for ST biopsy is shown next to the corresponding patient. (D) Lining IHC score for CD68⁺ cells; high/moderate versus LDA patients with RA, *p=0.03; high/moderate versus remission patients with RA, **p<0.001; LDA versus remission patients with RA, p=0.39. (E) Sublining IHC score for CD68⁺ cells; high/moderate versus LDA patients with RA, **p=0.01; high/moderate versus remission patients with RA, **p<0.001; LDA versus remission patients with RA, p=0.28. (F) Lining IHC score for CD20⁺ cells; high/moderate versus LDA patients RA, **p=0.01; high/moderate versus remission patients with RA, **p<0.001; LDA versus remission patients with RA, p=0.49. (G) Sublining IHC score for CD20⁺ cells; high/moderate versus LDA patients with RA, *p=0.05; high/moderate versus remission patients with RA, *p=0.02; LDA versus remission patients with RA, p=0.65. (H) Lining IHC score for CD3⁺ cells; high/moderate versus LDA patients with RA, *p=0.04; high/moderate versus remission patients with RA, **p=0.002; LDA versus remission patients with RA, p=0.92. (I) Sublining IHC score for CD3⁺ cells; high/moderate versus LDA patients with RA, *p=0.05; high/moderate versus remission patients with RA, **p=0.003; LDA versus remission patients with RA, p=0.29.

Figure 2

(A–D) IHC for CD31⁺ vessels on ST of patients with rheumatoid arthritis (RA) in remission, in low disease activity (LDA) and in high/moderate disease. (A) Example photos of CD31 (brown) staining of ST from patient with high/moderate RA (a, b) (magnification 20×); corresponding ultrasound assessment (US) picture with PD scale (PD score=2) of the knee used for ST biopsy is shown. (B) Example photos of CD31 (brown) staining of ST from patient with RA in LDA (a, b) (magnification 20×); corresponding US picture with PD scale (PD score=0) of the knee used for ST biopsy is shown. (C) Example photos of CD31 (brown) staining of ST from patient with RA in remission (a, b) (magnification 20×); corresponding US picture with PD scale (PD score=0) of the knee used for ST biopsy is shown. (D) IHC score for CD31⁺ vessels in ST of enrolled cohorts; high/moderate versus LDA in patients with RA, **p<0.001; high/moderate versus remission in patients with RA, **p<0.001; LDA versus remission in patients with RA, p=0.57.

Figure 3

(A–E) Masson Trichrome Goldner with light green immunostaining on ST of patients with rheumatoid arthritis (RA) in remission, in low disease activity (LDA) and in high/moderate disease. (A) Example photos of collagen (green) staining of ST from high/moderate patient with RA (a, b) (magnification 20×); corresponding ultrasound assessment (US) picture with PD scale (PD score=2) of the knee used for ST biopsy is shown. (B) Example photos of collagen (green) staining of ST from patient with RA in LDA (a, b) (magnification 20×); corresponding US picture with PD scale (PD score=0) of the knee used for ST biopsy is shown. (C) Example photos of collagen (green) staining of ST from patient with RA in remission (a, b) (magnification 20×); corresponding US picture with PD scale (PD score=0) of the knee used for ST biopsy is shown. (D) Lining IHC score for collagen in ST of enrolled cohorts; high/moderate versus LDA patients with RA, p=0.03; LDA versus remission patients with RA, p=0.10; high/moderate versus remission patients with RA, p<0.001. (E) Sublining IHC score for collagen in ST of enrolled cohorts; high/moderate versus LDA patients with RA, **p<0.001; LDA versus remission patients with RA, p=0.10; high/moderate versus remission patients with RA, **p<0.001.

Figure 4

(A–I) IHC staining for CD68/CD21, CD3/CD20 and CD31 on ST of power Doppler (PDUS)-negative patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in disease remission. (A) Example photos of CD68 (red)/CD21 (brown) (A^a), CD3 (red)/CD20 (brown) (A^b) and CD31 (brown) (A^c) staining of ST biopsies from patients with RA in remission (magnification 20×); corresponding ultrasound assessment (US) picture with PD scale (PD score=0) of the knee used for ST biopsy is shown. (B) Example photos of CD68 (red)/CD21 (brown) (B^a), CD3 (red)/CD20 (brown) (B^b) and CD31 (brown) (B^c) staining of ST biopsies from patients with PsA in remission (magnification 20×); corresponding US picture with PD scale (PD score=0) of the knee used for ST biopsy is shown. (C) Lining IHC score for CD68⁺ cells; patients with PsA versus RA, p=0.12. (D) Sublining IHC score for CD68⁺ cells; patients with PsA versus RA, *p=0.02. (E) Lining IHC score for CD20⁺ cells; patients with PsA versus RA, p=0.13. (F) Sublining IHC score for CD20⁺ cells; patients with PsA versus RA, p=0.22. (G) Lining IHC score for CD3⁺ cells; patients with PsA versus RA, p=0.29. (H) Sublining IHC score for CD3⁺ cells; patients with PsA versus RA, *p=0.04. (I) IHC score for CD31⁺ vessels; patients with PsA versus RA, **p<0.001.