Rheumatoid meningitis in the absence of active synovitis: A potential association of semaphorin 4A.

Rheumatoid meningitis (RM) is a rare complication that can develop even in patients with inactive rheumatoid arthritis (RA). Currently, there are no reliable indicators that reflect the disease activity of RM, and its pathogenesis remains poorly understood. Herein, we presented three cases of RM without active synovitis and investigated the possible association between RM and semaphorin 4A (Sema4A). Two of the three patients with RM developed sudden onset of seizures, while one patient exhibited a slowly progressive gait disturbance and cognitive impairment. All the patients had inactive synovitis, positive anti-cyclic citrullinated peptide antibodies in the serum, high-intensity lesions on the cerebral surface on head magnetic resonance imaging, or a favorable response to glucocorticoids. Serum and cerebrospinal fluid (CSF) Sema4A levels in patients with RM were elevated during the acute phase compared to those in the remission phase. Serum Sema4A was significantly increased in patients with RM than in RA controls (23.8 ng/ml versus 7.48 ng/ml, p = 0.014), although there were no significant differences in RA disease activity between the two groups. Sema4A was expressed in a few infiltrating cells and stromal tissues of the RM leptomeninges. This is the first report to demonstrate that serum and CSF Sema4A levels correlate with the disease activity of RM sine active synovitis. The expression of Sema4A in the leptomeninges may be associated with RM pathogenesis.