Immune‐mediated axonal dysfunction in seropositive and seronegative primary Sjögren’s syndrome

Abstract

Objective: The present study investigates the peripheral neuropathy in Primary Sj€ ogren's syndrome (pSS) using the nerve excitability test to further elucidate how peripheral nerves are affected by the autoantibodies. Methods: Each patient received clinical evaluation, examination for anti-SSA/Ro and anti-SSB/ La antibodies titer, paired motor and sensory nerve excitability test, thermal quantitative sensory test (QST), and nerve conduction study (NCS). Results: A total of 40 pSS patients wasenrolled. Motor axonal study of the pSS with positive anti-SSA/Ro or anti-SSB/La antibodies (n = 28) was found to have increased stimulus for 50% compound muscle action potential (CMAP) (P < 0.05), increased rheobase (P < 0.01), increased minimum I/V slope (P < 0.01) and hyperpolarizing I/V slope (P < 0.05), increased relative refractory period (RRP, P < 0.001), decreased accommodation of threshold electrotonus toward depolarizing current (P < 0.05), and increased accommodation toward hyperpolarizing current (P < 0.05). Seronegative pSS (n = 10) showed much less prominent motor axonal changes, showing only increased minimum I/V slope (P < 0.05). Sensory axonal study in seropositive pSS patients is found to have increased stimulus for 50% sensory nerve action potential (SNAP) (P < 0.01), decreased latency (P < 0.01), increased RRP (P < 0.01), and increased subexcitability (P < 0.05). Seronegative pSS patients have shown no significant sensory axonal changes. Thermal QST showed more prominent abnormalities in seronegative pSS compared to seropositive pSS. Interpretation: Anti-SSA/Ro and anti-SSB/La autoantibodies might cause dysfunction in nodal and internodal region of the axon and small nerve fibers; meanwhile, autoreactive antibodies in seronegative pSS mainly affect small nerve fibers. Thus, the underlying pathophysiology for the two types of pSS is different.

Decreased Protein Levels and Vitamin B12 Plasma Concentration in Primary Sjögren Syndrome are Associated with Peripheral Neuropathy: A Case-Control Study

“…A quite interesting finding was the increased number of mixed peripheral neuropathy, meaning that a demyelinating mechanism was associated with axonal damage, which is consistent with previously published data [40]. Myelin sheath damage is documented in pSS in the context of both vasa nervorum inflammation and autoimmune mediated mechanisms [41,42]. Only one study had priorly identified a majority of demyelinating pattern in Sjögren's peripheral neuropathy, reporting subclinical demyelination in 24% of the patients [43].…”

Clinical significance of anti-SSA/Ro antibody in Neuromyelitis optica spectrum disorders

“…The serum AQP4-IgG was easier to bind to the target antigen on the foot of astrocytes in the CNS and gave rise to an inflammatory cascade reaction that resulted in brain injury and neurological dysfunction. Another explanation is that the anti-SSA/Ro antibody combined with the cell surface SSA antigen causes nerve pathological changes, including the degeneration of axons and the loss of myelinated fiber in certain circumstances (Tani et al, 2020). Other studies found that "the anti-SSA/Ro antibody up-regulates the expression of inflammatory cytokines by triggering pathways of tumor necrosis factor (TNF) converting enzyme, TNF-α and nuclear factor-κB (NF-κB)" (Lisi et al, 2012).…”

Primary Sjögren syndrome‐related peripheral neuropathy: A systematic review and meta‐analysis

“…The study selection process is illustrated in the PRISMA chart (Figure 1). All of the 49 studies that met our inclusion criteria [19–67] were of an observational nature. The majority of the papers were published by research teams that included both rheumatologists/internists and neurologists ( n = 31) followed by research teams that included either only rheumatologists/internists ( n = 12) or only neurologists ( n = 6).…”