Epstein-Barr virus-specific intrathecal oligoclonal IgG production in relapsing-remitting multiple sclerosis is limited to a subset of patients and is composed of low-affinity antibodies

Table 4 Cerebrospinal fluid (CSF) and serum levels (median and IQR) and intrathecal synthesis of anti-Epstein Barr nuclear antigen 1 (EBNA-1) and anti-viral capsid antigen (VCA) IgG in patients with relapsing-remitting multiple sclerosis (RRMS), other inflammatory neurological disorders (OIND) and noninflammatory neurological disorders (NIND)

	Anti-EBNA-1 IgG			Anti-VCA IgG
	CSF levels (AU)	Serum levels (AU)	AI >1.5	CSF levels (AU)	Serum levels (AU)	AI >1.5
	Median; IQR	Median; IQR	n/total (%)	Median; IQR	Median; IQR	n/total (%)
Total RRMS (n = 100)	79.4; 37.5 to 174.3^a	52,056; 23,274 to 94,815^{c, d}	6/100 (6%)	36.4; 0.0 to 74.2	18962; 10659 to 46669	2/100 (2%)
CA RRMS (n = 77)	74.8; 38.2 to 167.7	41,783; 21,479 to 83,254	4/77 (5.2%)	41.9; 0.0 to 83.1	22546; 12433 to 51763	0/77 (0%)
CS RRMS (n = 23)	100.4; 51.0 to 272.7	59833; 36072 to 261044	2/23 (8.7%)	21.1; 0.0 to 59.9	14240; 6632 to 32515	2/23 (8.7%)
Gd + RRMS (n = 37)	90.4; 36.7 to 238.7	39325; 21479 to 105629	3/37 (8.1%)	23.7; 0.0 to 60.9	16836; 12476 to 37484	0/37 (0%)
Gd- RRMS (n = 63)	79.4; 43.3 to 139.0	53092; 27500 to 84551	3/63 (4.8%)	38.9; 0.0 to 85.1	21335; 10036 to 47672	2/63 (3.4%)
OIND (n = 100)	73.1; 31.0 to 151.6^b	23503; 10386 to 44089	6/100 (6%)	82.7; 30.3 to 294.1^{e, f}	29938; 8846 to 65475	5/100 (5%)
NIND (n = 100)	49.7; 15.9 to 118.9	24383; 7252 to 54754	2/100 (2%)	39.1; 0.0 to 130.8	28056; 12281 to 53124	1/100 (1%)

CSF anti-EBNA-1 IgG levels (Mann- Whitney with Bonferroni correction): ^aMS versus NIND (p <0.01); ^bOIND versus NIND (p <0.05). Serum anti-EBNA-1 IgG levels (Mann- Whitney with Bonferroni correction): ^cMS versus OIND (p <0.0001); ^dMS versus NIND (p <0.0001). CSF anti-VCA IgG levels (Mann- Whitney with Bonferroni correction): ^eOIND versus MS (p <0.0001); ^fOIND versus NIND (p <0.01). AI >1.5, antibody index abnormal values indicative of EBV-specific intrathecal synthesis; AU, arbitrary units; CA, clinically active (presence of relapse at entry); CS, clinically stable (absence of relapse at entry); Gd +, appearance of gadolium enhancing lesions on magnetic resonance imaging (MRI); Gd- , no evidence of gadolium enhancing on MRI; IQR, Interquartile Range; MS, multiple sclerosis; NIND, noninflammatory neurological diseases; OIND, other inflammatory neurological diseases.

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