Background IgG4+ plasma cells, eosinophil infiltration and fiber deposit are part of histological characteristics of IgG4-related disease. Our previous study showed elevated IgG4 may define specific clinical phenotype of RA (Mediators Inflamm, 2014). However, whether the above three characteristics involve in RA synovitis remains elusive.
Objectives To explore whether IgG4+ plasma cells, eosinophil infiltration and fiber deposit present in RA synovium and their correlation with severity of synovitis.
Methods Synovial tissue samples were obtained by closed-needle biopsy from inflamed knee of consecutive patients with active RA. Eosinophil density and synovitis score were evaluated under H&E staining. Densities of IgG4+ plasma cells, CD68+ macrophages, CD3+ T cells, CD20+ B cells, CD38+ plasma cells and microvascular count (identified by CD34+ endothelial cells) were determined. Fiber ratio defined as percentage of area occupied by fiber in synovium was determined under Masson's trichrome staining (a specific staining for collagenous fiber).
Results (1) Among 73 RA patients enrolled, 79% were female, age (median and IQR, similarly hereinafter) was 55 (47–62) years, disease duration was 36 (12–108) months and DAS28 was 5.3 (4.5–6.2).
(2) IgG4 expressed strongly in the cytoplasm of sublining plasma cell. IgG4+ plasma cell was 104 (27–243) /mm2 and correlated positively with ESR, CRP, total synovitis score and its three subscores (lining hyperplasia, inflammatory infiltration and stroma activation) and CD3+, CD20+, CD38+, CD68+ cell count (r=0.259–0.726, all p<0.05).
(3) Eosinophils with coarse granular cytoplasm and usually bilobate nucleus infiltrated in synovium subling (Fig.1A). The eosinophil count was 3 (2–10)/mm2 and correlated positively with 28SJC or CDAI (r=0.382–0.396, both p<0.05). 38% (28/73) of patient had synovial eosinophil infiltration. IgG4+ plasma cell count, total synovitis score or CD3+, CD20+, CD38+, CD68+ cell count is higher in patients with eosinophil infiltration (n=28) than patients without eosinophil infiltration (n=45; all p<0.05).
(4) Synovial collagenous fiber is identified by Masson's trichrome staining (Fig.1B). Fiber ratio was 27% (17%–37%) and correlated positively with disease duration, total synovitis score, stroma activation subscore (r=0.241–0.306, all p<0.05). Patients with synovial fiber ratio≥25% (n=43) had higher CD68+ cell count or CD34+ microvessel count than those with fiber ratio <25% (n=30, all p<0.05).
(5) Patients were divided into high-grade synovitis group (synovitis score >4, n=37) and low-grade synovits group (synovitis score≤4, n=36). IgG4+ plasma cells in high-grade synovits group was significantly higher than that in low-grade synovits group [186 (86–304) vs 54 (9–106) /mm2, p<0.05]. No significant difference of eosinophil infiltration or fiber deposit between these two groups (p>0.05). Receiver operating characteristic (ROC) analysis showed IgG4+ plasma cells can discriminate low-grade synovitis from high-grade synovits and the tradeoff value was 162/mm2 with sensitivity of 59% and specificity of 86% (AUC=0.754, 95%CI: 0.642–0.867, p<0.001).
Conclusions Our results showed that IgG4+ plasma cells, eosinophil infiltration and fiber deposit which are histological characteristics of IgG4-related disease can be seen in RA synovium and correlate with severity of synovitis in RA.
Disclosure of Interest None declared
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