Ectopic Germinal Centers and IgG4-Producing Plasmacytes Observed in Synovia of HLA-B27+ Ankylosing Spondylitis Patients with Advanced Hip Involvement

Abstract

Introduction. Ectopic lymphoid neogenesis and the presence of IgG4-positive plasmacytes have been confirmed in chronic inflammatory sclerosing diseases. This study aims to investigate hip synovial tissues of ankylosing spondylitis (AS) patients for IgG4-positive plasma cells and ectopic lymphoid tissues with germinal centers (GCs). Methods. Synovial samples were collected from 7 AS patients who received total hip replacement and were evaluated using immunohistochemistry for the presence of CD20+ B-cells, CD3+ T-cells, CD21+ follicular dendritic cells (FDC), and CD38+ plasma cells. Furthermore, immunoglobulin G (IgG and IgG4), IgA, IgM, and complement components C3d and C4d in synovia were evaluated. Both synovial CD21+ FDCs and IgG4-producing plasmacytes were analyzed. Results. All seven patients had severe fibrosis. Massive infiltrations of lymphocytes were found in 5 out of 7 patients' synovia. Ectopic lymphoid tissues with CD21+ FDC networks and IgG4-positive plasma cells were observed coincidentally in two patients' synovia. Conclusion. The pathophysiological mechanism of AS patients' hip damage might be related to the coincidental presence of ectopic lymphoid tissue with FDCs network and IgG4-positive plasma cells identified here for the first time in AS patients' inflamed synovial tissue.

Figure 1

Radiographic findings in AS patients with advanced hip joint disease. (a) Case 3; (b) case 5; (c) case 6; and (d) case 7.

Figure 2

Histologic findings and expression of CD molecules in case 5. (a) Staining with hematoxylin and eosin [H&E]. (b) CD21-positive FDC networks (DAB staining, 200x); (c) numerous CD20 positive B-cells in lymphoid neogenesis (DAB staining, 200x); and (d) Numerous CD3 positive T-cells in lymphoid neogenesis (DAB staining, 200x).

Figure 3

Plasma cells in synovial tissue. (a) CD38 positive plasma cells near lymphocyte follicles in case 5 (DAB staining, 200x); (b) massive IgG-positive plasma cell presence in case 5 (AEC staining, 200x); (c) numerous IgG4-positive plasma cell in case 5 (AEC staining, 200x); and (d) IgG4-positive plasma cells in case 6 (AEC staining, 200x).