Tyro3 and Gas6 are associated with white matter and myelin integrity in multiple sclerosis

Table 3 Multiple linear regression models investigating the associations of Tyro3, Axl, Mer and Gas6 at baseline and 12 month follow-up with brain volumes and change in brain volumes in patients with RRMS

	WM baseline^c		MyC baseline^c		GM baseline^c		BPF baseline^c
	β (95%CI)	p-value	β (95%CI)	p-value	β (95%CI)	p-value	β (95%CI)	p-value
Tyro3 (ng/mL)^a	39.3 (9.65 to 68.9)	0.011	11.94 (− 0.05 to 23.9)	0.051	26.3 (− 3.7 to 56.3)	0.084	0.008 (− 0.007 to 0.022)	0.3
Axl (ng/mL)^a	5.08 (− 32.1 to 42.3)	0.78	− 2.3 (− 16.4 to 11.8)	0.74	14.1 (− 17.2 to 45.4)	0.36	0.0003 (− 0.01 to 0.01)	0.96
Mer (ng/mL)^a	185.8 (23.7 to 348)	0.026	55.5 (− 8.9 to 119.8)	0.089	43.5 (− 116.2 to 203.3)	0.6	0.045 (− 0.023 to 0.114)	0.18
Gas6 (ng/mL)^a	19.7 (2.75 to 36.6)	0.024	6.74 (0.11 to 13.4)	0.046	2.9 (− 14.2 to 19.9)	0.73	0.006 (− 0.002 to 0.013)	0.13

	WM 12 m follow-up^d		MyC 12 m follow-up^d		GM 12 m follow-up^d		BPF 12 m follow-up^d
Tyro3 (ng/mL)^b	18.1 (− 23.3 to 48.4)	0.23	5.7 (− 6.5 to 17.9)	0.34	16.4 (− 14.5 to 47.3)	0.28	0.0003 (− 0.02 to 0.02)	0.97
Axl (ng/mL)^b	15.8 (− 24.7 to 56.5)	0.3	6.9 (− 8.8 to 22.5)	0.37	− 0.23 (− 42.8 to 48.9)	0.99	0.00004 (− 0.02 to 0.02)	0.96
Mer (ng/mL)^b	134.3 (− 58.03 to 326.6)	0.16	41.9 (− 35.9 to 119.7)	0.3	129.5 (− 51.7 to 310.7)	0.15	− 0.02 (− 0.11 to 0.073)	0.67
Gas6 (ng/mL)^b	12.3 (− 3.7 to 28.2)	0.13	3.8 (− 2.7 to 10.3)	0.24	2.1 (− 14.4 to 18.6)	0.67	0.002 (− 0.006 to 0.01)	0.6

	WMΔ^d		MyCΔ^d		GMΔ^d		BPFΔ^d
	β (95%CI)	p-value	β (95%CI)	p-value	β (95%CI)	p-value	β (95%CI)	p-value
Tyro3 (ng/mL)^a	25.5 (6.11 to 44.96)	0.012	7.95 (1.84 to 14.07)	0.012	6.9 (− 9.24 to 23.04)	0.39	0.007 (− 0.001 to 0.026)	0.098
Axl (ng/mL)^a	3.53 (− 18.54 to 25.61)	0.74	− 0.45 (− 7.43 to 6.53)	0.89	12.56 (− 3.4 to 28.53)	0.12	0.008 (− 0.005 to 0.21)	0.2
Mer (ng/mL)^a	56.2 (− 51.9 to 164.24)	0.29	12.86 (− 21.6 to 47.3)	0.45	24.12 (− 58 to 106.25)	0.55	0.022 (− 0.25 to 0.68)	0.35
Gas6 (ng/mL)^a	11.4 (0.42 to 22.4)	0.042	4.4 (1.04 to 7.75)	0.012	− 4.67 (− 12.86 to 3.53)	0.25	− 3223E−5 (− 0.005 to 0.005)	0.99

WM, white matter; MyC, myelin content; GM, gray matter; BPF, brain parenchymal fraction; CI, confidence interval
Bold text symbolizes p < 0.05
^aBaseline
^b12 month follow-up
^cMultivariable models are adjusted for age, sex, and disease duration
^dMultivariable models are adjusted for age, sex, disease duration, and DMT exposure

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