Zhao Chenxu, Yu Yang, Liu Jumei, Lu Guizhi, Li Ting, Gao Ying, Zhang Junqing, Guo Xiaohui
Department of Endocrinology, Peking University First Hospital, No. 8 Xi Shi Ku Street, Xicheng District, Beijing 100034, China; Department of Endocrinology, Hebei Medical University First Affiliated Hospital, No. 89 Dong Gang Road, Yuhua District, Shijiazhuang, China.
Department of Endocrinology, Peking University First Hospital, No. 8 Xi Shi Ku Street, Xicheng District, Beijing 100034, China.
Int Immunopharmacol. 2022 May;106:108636. doi: 10.1016/j.intimp.2022.108636. Epub 2022 Feb 24.
To investigate complement components expression in both thyroid tissues and serum from patients with Hashimoto's thyroiditis (HT), Graves' disease (GD), and papillary thyroid cancer (PTC).
C1q, mannose binding lectin (MBL), Bb, C4d, C3d and membrane attack complex (MAC) (C5b-9) deposition and complement regulate proteins (CD46, CD55 and CD59) expression in thyroid tissues from HT, GD, PTC, and control groups were examined by IHC. C1q, MBL, Bb, C4d, C3a, and soluble C5b-9 (sC5b-9) serum levels in the HT, GD, PTC, and healthy donor (HD) groups were measured by ELISAs.
MAC deposition was detected in thyroid tissues in the HT, GD and PTC groups, but not the control group. MBL, Bb, C4d, C3d and MAC staining intensities in thyroid tissues were significantly higher in the HT and PTC groups than in the control group (all P < 0.05). The C1q level was higher in HT tissues than in control tissues (both P < 0.05). No complement component had a significant difference in staining intensities between the GD and control groups. CD55 and CD59 expression levels in thyroid tissues were higher in the PTC group than in the HT, GD and control groups (all P < 0.05). Similarly, CD46 levels were higher in HT tissues than in control tissues. Bb, C4d, C3a and sC5b-9 serum levels were significantly increased in HT, GD and PTC patients compared with HDs (all P < 0.05).
Complement is overactivated in HT and PTC, but not in GD. All the three pathways are activated in HT, and the MBL and alternative complement pathways are activated in PTC. These distinct complement activation profiles may participate in HT, GD and PTC pathogenesis.
研究桥本甲状腺炎(HT)、格雷夫斯病(GD)和甲状腺乳头状癌(PTC)患者甲状腺组织及血清中补体成分的表达情况。
采用免疫组化法检测HT、GD、PTC及对照组甲状腺组织中C1q、甘露糖结合凝集素(MBL)、Bb、C4d、C3d和膜攻击复合物(MAC)(C5b-9)的沉积以及补体调节蛋白(CD46、CD55和CD59)的表达。采用酶联免疫吸附测定法检测HT、GD、PTC及健康供体(HD)组血清中C1q、MBL、Bb、C4d、C3a和可溶性C5b-9(sC5b-9)的水平。
HT、GD和PTC组甲状腺组织中检测到MAC沉积,而对照组未检测到。HT和PTC组甲状腺组织中MBL、Bb、C4d、C3d和MAC的染色强度显著高于对照组(均P<0.05)。HT组织中C1q水平高于对照组织(均P<0.05)。GD组与对照组之间补体成分的染色强度无显著差异。PTC组甲状腺组织中CD55和CD59的表达水平高于HT、GD和对照组(均P<0.05)。同样,HT组织中CD46水平高于对照组织。与HD相比,HT、GD和PTC患者血清中Bb、C4d、C3a和sC5b-9水平显著升高(均P<0.05)。
补体在HT和PTC中过度激活,而在GD中未过度激活。HT中所有三条途径均被激活,PTC中MBL和替代补体途径被激活。这些不同的补体激活模式可能参与HT、GD和PTC的发病机制。