Objective To explore the pathological changes of peripheral neuropathy in Sjogren's syndrome and the role of macrophages in it. Methods and results Methods: Sural nerve biopsy was performed in 12 patients diagnosed with primary Sjogren’s syndrome associated peripheral nervous system involvement (pSS-PN) and 3 traumatic amputees. First, we collected clinical data and electromyography (EMG) findings from 12 pSS-PN patients. Histological assessment of sural nerve specimens was subsequently performed using hematoxylin–eosin (HE) and neurofilament protein (NF) staining under light microscopy. The ultrastructural changes of peripheral nerves were observed by transmission electron microscopy (TEM). Macrophage types were labeled with CD206 and iNOS antibodies by immunohistochemistry and immunofluorescence. The 3 control cases underwent HE staining, CD68 IHC, and TEM. Results: Patients with pSS-PN typically present with symptoms such as neuropathic pain, limb weakness, and sensory disturbances. HE and NF staining revealed mild-to-severe damage to both myelinated and unmyelinated fibers in peripheral nerves, with some cases showing predominant small‑vessel inflammation. Immunohistochemistry and immunofluorescence demonstrated infiltration of CD68⁺ macrophages—predominantly of the M2 phenotype—around small vessels and within nerve bundles. Electron microscopy further illustrated that macrophages progressively strip and engulf myelin sheaths, leaving bare axons. In addition, inflammatory cell infiltration within vasa nervorum led to blood‑cell stasis, endothelial damage, platelet aggregation, and eventual vascular obstruction and collapse. Conclusion These clinicopathological observations establish vasculitic peripheral neuropathy as the predominant form of pSS‑PN. This prominent infiltration of M2 macrophages in the affected nerves suggests that they play a pivotal role in the pathogenesis of pSS‑PN, potentially offering a novel therapeutic direction for this condition. <Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> Key Points • Vasculitic peripheral neuropathy is the main pattern of pSS‑PN, with M2 macrophages heavily infiltrating affected nerves. • Ultrastructural evidence shows macrophages actively stripping myelin sheaths, leading to axonal exposure. • These findings highlight M2 macrophages as a potential new therapeutic direction for pSS-PN. </entry> </row> </tbody> </tgroup> </Table>

Macrophage 2 plays an important role in axonal lesions and vasculitis in Sjogren's syndrome complicated with peripheral neuropathy

期刊论文
发表日期：

2026年4月8日

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Jiaman Zheng,
Liying Xu,
Jiayu Zhang,
Jiying Wei,
Ziqi Li,
Huihao Ye,
Xinhao Chen,
Haishan Jiang,
Min Yang,
Hui Zheng,
Chao Yuan

摘要

Objective

To explore the pathological changes of peripheral neuropathy in Sjogren's syndrome and the role of macrophages in it.

Methods and results

Methods: Sural nerve biopsy was performed in 12 patients diagnosed with primary Sjogren’s syndrome associated peripheral nervous system involvement (pSS-PN) and 3 traumatic amputees. First, we collected clinical data and electromyography (EMG) findings from 12 pSS-PN patients. Histological assessment of sural nerve specimens was subsequently performed using hematoxylin–eosin (HE) and neurofilament protein (NF) staining under light microscopy. The ultrastructural changes of peripheral nerves were observed by transmission electron microscopy (TEM). Macrophage types were labeled with CD206 and iNOS antibodies by immunohistochemistry and immunofluorescence. The 3 control cases underwent HE staining, CD68 IHC, and TEM.

Results: Patients with pSS-PN typically present with symptoms such as neuropathic pain, limb weakness, and sensory disturbances. HE and NF staining revealed mild-to-severe damage to both myelinated and unmyelinated fibers in peripheral nerves, with some cases showing predominant small‑vessel inflammation. Immunohistochemistry and immunofluorescence demonstrated infiltration of CD68⁺ macrophages—predominantly of the M2 phenotype—around small vessels and within nerve bundles. Electron microscopy further illustrated that macrophages progressively strip and engulf myelin sheaths, leaving bare axons. In addition, inflammatory cell infiltration within vasa nervorum led to blood‑cell stasis, endothelial damage, platelet aggregation, and eventual vascular obstruction and collapse.

Conclusion

These clinicopathological observations establish vasculitic peripheral neuropathy as the predominant form of pSS‑PN. This prominent infiltration of M2 macrophages in the affected nerves suggests that they play a pivotal role in the pathogenesis of pSS‑PN, potentially offering a novel therapeutic direction for this condition.

Key Points

• Vasculitic peripheral neuropathy is the main pattern of pSS‑PN, with M2 macrophages heavily infiltrating affected nerves.

• Ultrastructural evidence shows macrophages actively stripping myelin sheaths, leading to axonal exposure.

• These findings highlight M2 macrophages as a potential new therapeutic direction for pSS-PN.