Table 1.

Diagnostic value of κ‑free light chain index in patients with multiple sclerosis

Reference	Type of controlsa	No. of control subjects	No. of MS patients	McDonald criteria	Laboratory method	κ‑FLC index cut-off	Elevated κ‑FLC index in MS, n	Sensitivity, %	Normal κ‑FLC index in controls, n	Specificity, %	OCB positive in MS, n	Sensitivity, %	OCB negative in controls, n	Specificity, %
[25]	NIND/IND/PIND	1149	75	2010	Ne/N Latex	9.58	69	92	1115	97	71	95	1072	93
[26]		299	146	2010/2017	Tu/Freelite	5.8	76	52	282	94	54	37	299	100
[28]		197	45	2017		6.6	42	93	172	87	40	89	179	91
[29]	NIND/IND	105	71	Not specified	Ne/N Latex	12.3	68	96	105	100	65	92	99	94
[30]		85	37	Not specified	Ne/Freelite	5.9	28	76	77	91	33	89	69	81
[31]		253	67	2010		10.463	58	87	193	76	63	94	187	74
[33]		83	59	Not specified	Tu/Freelite	12.45	46	78	64	77	46	78	66	80
[32]		258	127	2017	Ne/N Latex	5.0	122	96	208	81	123	97	214	83
[24]		219	284	2005/2010	Tu/Freelite	6.6	264	93	181	83	245	86	202	92
[34]		42	34	2017		9.4	32	94	29	68	34	100	38	90
[35]		240	133	2017	Ne/N Latex	5.0	124	93	205	85	127	96	204	85
[27]		456	84	2017	Tu/Freelite	6.2	75	89	383	85	71	85	405	89
[36]	NIND	368	41	2001/2005	Ne/Freelite	5.9	40	98	318	86	39	95	338	92
[23]		60	60	2005		5.9	56	93	57	95	56	93	59	98
[37]		97	96	2010	T/Freelite	7.5	87	91	88	91	79	82	91	94
[40]		30	68	2017	N/Freelite	3.09	49	72	30	100	38	56	30	100
[38]		50	80	2010	N/N Latex	5.3	77	96	48	96	73	91	49	98
[39]	HC/SC	60	62	2010		7.15	56	90	60	100	54	87	60	100

A search of the electronic database PubMed was performed on November 17, 2021 using the terms “multiple sclerosis” and “free light chains” and limited to the time period between January 1, 2005 and November 17, 2021. Titles and abstracts of identified articles written in English were screened and the full text of potentially relevant articles were assessed for inclusion criteria. Studies were included if they were original articles investigating the diagnostic value of κ‑FLC index in patients with MS compared to other neurological diseases and used nephelometry/turbidimetry for κ‑FLC measurement. κ-FLC kappa free light chain, OCB oligoclonal bands

Following original articles were included: [25] Senel 2019, [26] Ferraro 2020, Eur J Neurol, [28] Sanz Diaz 2021, [29] Pieri 2017, [30] Valencia-Vera 2018, [31] Gurtner 2018, [33] Bayart 2018, [32] Crespi 2019, [24] Leurs 2020, [34] Gudowska-Sawczuk 2020, [35] Vecchio 2020, [27] Ferraro 2020, Diagnostics (Basel), [36] Presslauer 2008, [23] Presslauer 2016, [37] Christiansen 2018, [40] Altinier 2019, [38] Emersic 2019 and [39] Duell 2020.

The diagnostic value of κ‑FLC index and OCB was compared by a difference-in-differences model. Therefore, for each study, the difference of diagnostic sensitivity of κ‑FLC index and OCB (∆sensitivity), as well as the difference of diagnostic specificity of κ‑FLC index and OCB (∆specificity) was calculated. Then, also the sum of ∆sensitivity and ∆specificity was calculated (∆overall). Finally, the mean of all ∆values was calculated. This statistical analysis revealed a mean ∆sensitivity of 2%, ∆specificity of −2%, and ∆overall of 0%. This result indicate that there is no difference in the diagnostic performance of κ‑FLC index and OCB to discriminate patients with MS from controls

HC healthy controls, IND inflammatory neurological disease controls (other than MS), MS multiple sclerosis, Ne Nephelometry, NIND non-inflammatory neurological disease controls, PIND peripheral inflammatory neurological disease controls, SC symptomatic controls, Tu Turbidimetry, κ‑FLC kappa free light chain, OCB oligoclonal bands

^aControl population of studies were labelled/categorized according to the “Consensus definitions and application guidelines for control groups in cerebrospinal fluid biomarker studies in multiple sclerosis” [42]