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. 2004 Sep 23;64(4):529–536. doi: 10.1136/ard.2003.018549

Histological evidence that infliximab treatment leads to downregulation of inflammation and tissue remodelling of the synovial membrane in spondyloarthropathy

E Kruithof 1, D Baeten 1, F Van den Bosch 1, H Mielants 1, E Veys 1, F De Keyser 1
PMCID: PMC1755461  PMID: 15388510

Abstract

Objective: To confirm and extend the immunopathological evidence of effects of infliximab on the synovium in active spondyloarthropathy.

Methods: Synovial biopsies obtained in patients with spondyloarthropathy at baseline and week 12 were stained and scored by two independent observers. Two study populations were evaluated: I, a cohort of 10 patients treated with 5 mg/kg infliximab at week 0, 2, and 6, plus three placebo treated patients; and II, a pooled cohort of 20 patients fulfilling identical inclusion and exclusion criteria and treated with the same loading dose regimen.

Results: In study population I, treatment with infliximab induced reduction in synovial lining layer thickness (p = 0.015), endothelial activation (E-selectin, p = 0.034), and inflammatory cell infiltration with neutrophils (p = 0.041), macrophages (p = 0.034), and T cells (p = 0.026), but not with B cells and plasma cells; no such trends were observed in the placebo treated patients. Besides confirming the highly significant downregulation of inflammation, analysis of cohort II showed structural changes such as normalisation of lining layer thickness (p = 0.030), reduction in the number of blood vessels (p = 0.039), and downregulation of follicular organisation (p = 0.050). No differences in histopathological response were observed between spondyloarthropathy subtypes.

Conclusions: Profound immunomodulatory changes in the synovium parallel the clinical benefit in patients with spondyloarthropathy treated with infliximab, independently of the subtype. The study provides histological evidence that TNFα blockade not only downregulates inflammation but also leads to tissue remodelling.

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Figure 1.

Figure 1

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 Immunomodulatory effect of infliximab (A = study population I, n = 10) or placebo (B = study population I, n = 3) on synovial histology in patients with active spondyloarthropathy. Synovial biopsies obtained at week 0 and week 12 were scored on a semiquantitative scale (0–3) by two independent observers (p value calculated using the paired Wilcoxon signed ranks test for study population I). Representative sections of the evaluation at baseline (C) and at week 12 (D) in infliximab treated patients (study population I) are shown, and the corresponding semiquantitative score for each picture is indicated. The variables evaluated included: the degree of inflammatory cell infiltration (score 2.5 at baseline, score 0.5 at week 12); the number of neutrophils (score 3 at baseline, score 0 at week 12); the number of CD3+ T cells (score 2 at baseline, score 0 at week 12); the number of CD20+ B cells (score 0 at baseline, score 2 at week 12); the number of CD38+ plasma cells (score 3 at baseline, score 3 at week 12); and the number of CD68+ macrophages (score 2 at baseline, score 1 at week 12).

Figure 2.

Figure 2

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 Tissue remodelling effect of infliximab (A = study population I, n = 10) or placebo (B = study population I, n = 3) on synovial histology in patients with active spondyloarthropathy. Synovial biopsies obtained at week 0 and week 12 were scored on a semiquantitative scale (0–3) by two independent observers (p value calculated using the paired Wilcoxon signed ranks test for study population I). Representative sections of the evaluation in infliximab treated patients (study population I) at baseline (C) and at week 12 (D) are shown, and the corresponding semiquantitative score for each picture is indicated. The variables evaluated included: the synovial lining layer thickness (score 2 at baseline, score 1 at week 12); the degree of vascularity (score 3 at baseline, score 1 at week 12); the number of CD146+ endothelial cells (score 3 at baseline, score 1 at week 12); endothelial expression of von Willebrand factor (score 3 at baseline, score 1 at week 12); the degree of follicular formation (score 2 at baseline, score 1,5 at week 12); and the presence of CD83+ dendritic cells (present at baseline, absent at week 12). NC, not calculable.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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