Role of macrophages in peripheral nervous system involvement in patient with primary Sjogren’s syndrome

Abstract

Abstract Aims: To explore the role of macrophage in peripheral nervous system involvement in patients with primary Sjogren’s syndrome. 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). The structural features of sural nerve stained by hematoxylin-eosin(HE) under light microscope. Immunohistochemistry and immunofluorescence staining were carried out to detect the distribution and polarization of macrophage in peripheral neuropathy, using CD206 and iNOS antibodies to label different types of macrophage. The ultrastructural changes of macrophage and peripheral nerves in pSS-PN were observed by transmission electron microscopy. Results: Sural nerve biopsies were performed in 12 patients with pSS-PN, including four men and eight women whose age was 50.4±16.3 years (means±SD) and the duration was 4.43±4.06 months (means±SD). HE staining showed different degrees of reduction of large and small myelinated fibers, NF staining showed various reduction of non-myelinated fibers (mild in 4 cases, moderate in 5 cases, and severe in 3 cases). Immunohistochemistry revealed that inflammatory cell infiltrated in nerve tracts and around blood vessels in 8 cases, and the remaining four patients presented with mixed peripheral neuropathy, mainly axonal damage. Immunofluorescence also revealed that CD68+ macrophages infiltrated in the small vessels and nerve bundles, and M2 macrophages were the main type. Ultrastructure enlarged by electron microscopy showed infiltration of macrophages around nerve fibers, which engulf nerve myelin and axons. In the early stage we can see local swelling and enlarged of axons, then atrophy of axons, and finally separation of axon membrane from myelin, small axis mutation, and loss of normal proportion to myelin. Conclusions: Macrophages play an important role in Sjogren's syndrome related peripheral neuropathy, and are involved in the occurrence of vasculitis, demyelination and axonal damage.