Using the IVW method as the primary evaluation standard, we detected that three immune cell traits had a protective effect against HSP: B cell (IgD- CD38- %lymphocyte) (OR = 0.814, 95% CI: 0.697-0.952, p = 0.0100), B cell (CD27 on T cell) (OR = 0.891, 95% CI: 0.818-0.970, p = 0.0076), and Treg (CD25 on CD39+ activated Treg) (OR = 0.813, 95% CI: 0.708-0.934, p = 0.0034). The gene discussed is CD27; the disease is hereditary spastic paraplegia.