The Mechinism Of Ectopic Germinal Centers In Labial Glands In The Pothogenesis Of Primary Sjogren’s Syndrome

Background. About1/5salivary glands biopsy in primary Sjogren’s syndrome (pSS) patients have Ectopic germinal centers (EGCs), their pathological role is still unclear. Our preliminary study found by HE staining that12.5%of pSS patients with the EGCs. To investigate the role of EGCs in pSS, we detected in the way of immunohistochemistry (IHC), cell flow analysis (FC) and enzyme-linked immunosorbent assay (ELISA) to find out the role of EGCs in local infiltration, circulatory migration, B lymphocytes differentiation or self-activation and T lymphocytes regulation of inflammation in pSS patients.Methods. CD21is stained to identify the dendritic cells network structure around the ectopic germinal centers through immunohistochemical method (IHC). All the subjects were divided into4groups:grade0group is normal control, grade1group (G1) with unorganized diffuse infiltrates in labila glands biopsy, grade2group (G2) with focal periductal T cell and B cell aggregates, grade3group (G3) with germinal center-like structures. To find out the role of EGCs, the differences of the B cells marker CD24, Th17cells marker IL17and chemokine CXCL13in labial glands paraffin sections among different groups, while CD24+CD19+B cells, IL17+CD4+cells and CXCR4, CXCR5cells in peripheral blood were also analyzed by FC and the concentration of the chemokine CXCL13, CXCL12were analyzed by method of ELISA. The clinical information of the pSS patients was evaluated simultaneously.Results. 1.8cases (21.1%) of38pSS patients have ectopic germinal centers2. CD24, IL17, CXCL13were only expressed by acinar and ductal epithelial cells in control and G1group. CD24, IL17, CXCL13were also found in the area of lymphocytes infiltration focus in the G2group. In G3group CD24was mainly in the follicular and marginal zones, IL17was mainly in the circumference of lymphocytes infiltration focus, while CXCL13was mainly surround the follicular zones.3. In patients with EGCs, there was no difference in expression of CD24, IL17and CXCL13between EGCs and the other inflamed focus in the labial glands. IL17and CD24were highly positive correlated.4. The average optical density of CD24, IL17, CXCL13and positive cell scores of IL17, CXCL13.are respectively as follow:CD24:G3> G2> G1, IL17:G3> G2> G1, CXCL13:G3> G1> G2.62.5%G3patients have higher scores and average optical density than upper limit of95%Cl of all3indexes.5. By comparison of the circulatory indexes with normal controls, Th17cells, CXCR4cells and plasma CXCL13were significantly higher in pSS patients. Th17cells and plasma CXCL13were positive correlated.6.Compare the relative indexes in the labial inflamed focus and peripheral blood in different groups:CD24and Th17cells in labial glands G3> G2> G1, peripheral blood CD19+CD24+B cells G3<G2<G1; peripheral blood Th17cells in G2> G1>G3; CXCL13positive cells in labial glands G3> G2> G1, plasma CXCL13G2> G1> G3, peripheral blood CXCR5+cells G1> G3> G2; plasma CXCL12G1> G3> G2, peripheral blood CXCR4+cells G2G2> G3> G1.7. G2group have higher SICCA corneal staining score than the G1group, but the other indexes were no significant differences among the groups. Conclusion,1. Ectopic germinal centers occur in moderate to severe focal lymphocytic infiltration of inflammation.2. The pSS patients with ectopic germinal center can mobilize more CD24-positive B lymphocytes from peripheral blood to the labial gland3. Th17is involved into the lymphocytes infiltration formation of ectopic germinal centers.4. CXCL13and the acceptor CXCR5participates the migration of lymphocytes to the labial glands as well as the formation of ectopic germinal centes.