Complex regional pain syndrome patient immunoglobulin M has pronociceptive effects in the skin and spinal cord of tibia fracture mice
Complex regional pain syndrome patient immunoglobulin M has pronociceptive effects in the skin and spinal cord of tibia fracture mice
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DOI：
10.1097/j.pain.0000000000001765
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发表时间：
2020-04-01
期刊：
影响因子：
7.4
通讯作者：
Kingery, Wade S.
中科院分区：
文献类型：
--
作者：
Guo, Tian-Zhi;Wei, Tzuping;Kingery, Wade S.
复杂区域疼痛综合征（CRPS）是一种创伤后自身免疫性疾病。以前，我们观察到，B细胞是在小鼠胫骨骨折模型中完全表达CRPS样变化所必需的，并且来自骨折小鼠的血清免疫球蛋白M（IgM）抗体在缺乏B细胞的muMT骨折小鼠中具有原伤害感受效应。目前的研究通过测量后爪异常性疼痛和减重变化来评估将CRPS患者血清或抗体注射到muMT骨折小鼠中的致痛效应。针对先前在骨折小鼠模型中鉴定的自身抗原测量复杂区域疼痛综合征血清结合。CRPS患者血清或IgM抗体在muMT骨折小鼠中全身注射时在骨折肢体中具有原伤害感受作用，但正常受试者血清和CRPS患者IgG抗体没有作用。此外，CRPS血清IgM抗体在注射到muMT骨折小鼠的骨折肢后爪皮肤或鞘内时具有原伤害感受效应。早期（损伤后1-12个月）CRPS患者（n = 20）的血清在全身注射后总是具有原伤害感受性，而慢性（损伤后>12个月）CRPS血清很少具有原伤害感受性（2/20例患者），而来自正常受试者（n = 20）和来自从矫形外科手术和/或骨折中恢复的无并发症患者（n = 15）的血清从不具有原伤害感受性。观察到角蛋白16、组蛋白3.2、γ肌动蛋白和α烯醇化酶自身抗原的CRPS血清IgM结合增加。我们假设CRPS患者IgM抗体结合到骨折小鼠皮肤和脊髓中的新抗原，以启动可能导致CRPS疾病过程的区域限制性原伤害性补体反应。
It has been proposed that complex regional pain syndrome (CRPS) is a post-traumatic autoimmune disease. Previously, we observed that B cells are required for the full expression of CRPS-like changes in a mouse tibia fracture model and that serum immunoglobulin M (IgM) antibodies from fracture mice have pronociceptive effects in muMT fracture mice lacking B cells. The current study evaluated the pronociceptive effects of injecting CRPS patient serum or antibodies into muMT fracture mice by measuring hind paw allodynia and unweighting changes. Complex regional pain syndrome serum binding was measured against autoantigens previously identified in the fracture mouse model. Both CRPS patient serum or IgM antibodies had pronociceptive effects in the fracture limb when injected systemically in muMT fracture mice, but normal subject serum and CRPS patient IgG antibodies had no effect. Furthermore, CRPS serum IgM antibodies had pronociceptive effects when injected into the fracture limb hind paw skin or intrathecally in the muMT fracture mice. Early (1-12 months after injury) CRPS patient (n = 20) sera were always pronociceptive after systemic injection, and chronic (>12 months after injury) CRPS sera were rarely pronociceptive (2/20 patients), while sera from normal subjects (n = 20) and from patients with uncomplicated recoveries from orthopedic surgery and/or fracture (n = 15) were never pronociceptive. Increased CRPS serum IgM binding was observed for keratin 16, histone 3.2, gamma actin, and alpha enolase autoantigens. We postulate that CRPS patient IgM antibodies bind to neoantigens in the fracture mouse skin and spinal cord to initiate a regionally restricted pronociceptive complement response potentially contributing to the CRPS disease process.