Kappa-Free Light Chains in CSF Predict Early Multiple Sclerosis Disease Activity

Abstract

ObjectiveTo investigate whether κ-free light chain (κ-FLC) index predicts multiple sclerosis (MS) disease activity independent of demographics, clinical characteristics, and MRI findings.MethodsPatients with early MS who had CSF and serum sampling at disease onset were followed for 4 years. At baseline, age, sex, type of symptoms, corticosteroid treatment, and number of T2 hyperintense (T2L) and contrast-enhancing T1 lesions (CELs) on MRI were determined. During follow-up, the occurrence of a second clinical attack and start of disease-modifying therapy (DMT) were registered. κ-FLCs were measured by nephelometry, and κ-FLC index calculated as [CSF κ-FLC/serum κ-FLC]/albumin quotient.ResultsA total of 88 patients at a mean age of 33 ± 10 years and female predominance of 68% were included; 38 (43%) patients experienced a second clinical attack during follow-up. In multivariate Cox regression analysis adjusting for age, sex, T2L, CEL, disease and follow-up duration, administration of corticosteroids at baseline and DMT during follow-up revealed that κ-FLC index predicts time to second clinical attack. Patients with κ-FLC index >100 (median value 147) at baseline had a twice as high probability for a second clinical attack within 12 months than patients with low κ-FLC index (median 28); within 24 months, the chance in patients with high κ-FLC index was 4 times as high as in patients with low κ-FLC index. The median time to second attack was 11 months in patients with high κ-FLC index whereas 36 months in those with low κ-FLC index.ConclusionHigh κ-FLC index predicts early MS disease activity.Classification of EvidenceThis study provides Class II evidence that in patients with early MS, high κ-FLC index is an independent risk factor for early second clinical attack.

The Increasing Role of Kappa Free Light Chains in the Diagnosis of Multiple Sclerosis

“…Over all studies, the mean prevalence of OCB positivity in MS patients was 94% (min-max: 85-100%) reflecting the importance of detection of intrathecal inflammation as a criterion for dissemination in time [24,[26][27][28][29]33,[42][43][44]47,48,55,56,[68][69][70][71][72][73][74][75]92]. Nevertheless, it has to be considered that some studies only included OCB-positive MS patients while other studies comprised a certain percentage of OCB-negative MS patients, thus leading the observed wide range of OCB prevalence [24,[26][27][28][29]33,[42][43][44]47,48,55,56,[68][69][70][71][72][73][74][75]92]. KFLC measurements, interpreted by different approaches, reached a mean diagnostic sensitivity of 94% (min-max: 72-100%) and specificity of 84% (min-max: 65-100%) in MS patients [24,…”

“…The index calculation may be employed for the evaluation of intrathecal synthesis of KFLC as well as for LFLC. Different studies applied KFLC indices varying between 0.92 and 20 and reached a mean diagnostic sensitivity of 87% (82%, 92%) and a mean diagnostic specificity of 87% in MS patients (83%, 91%) [19][20][21][22][23][24][27][28][29]33,42,[44][45][46][47][48][49][50][51]53,54,[56][57][58][59][60][61]64,65,[68][69][70][71][72][73][74][75][78][79][80][81][82]85,87,92]. It has to be considered that in some of these studies, the diagnostic utility of FLC in OCB-negative MS patients was investigated, leading to very low diagnostic sensitivity.…”

“…It has to be considered that in some of these studies, the diagnostic utility of FLC in OCB-negative MS patients was investigated, leading to very low diagnostic sensitivity. Some studies also investigated LFLC indices (cut-off 0.29-21.45) leading to lower mean sensitivity (64% (46%, 81%)) and specificity (83% (74%, 93%)) [19][20][21][22][23][24][27][28][29]33,42,[44][45][46][47][48][49][50][51]53,54,[56][57][58][59][60][61]64,65,[68][69][70][71][72][73][74][75][78][79][80][81][82]85,87,92]. FLC indices implement Q Albumin and therefore are more accurate in detecting the intrathecally synthesized portion and differentiating it from FLC, which diffused from blood into CSF.…”

“…Thus, studies, which applied the revised McDonald criteria of 2017 in order to evaluate the performance of KFLC in the diagnosis of MS and CIS, constitute the most relevant investigations for this review (Tables 3 and 4) [16]. Over all studies, the mean prevalence of OCB positivity in MS patients was 94% (min-max: 85-100%) reflecting the importance of detection of intrathecal inflammation as a criterion for dissemination in time [24,[26][27][28][29]33,[42][43][44]47,48,55,56,[68][69][70][71][72][73][74][75]92]. Nevertheless, it has to be considered that some studies only included OCB-positive MS patients while other studies comprised a certain percentage of OCB-negative MS patients, thus leading the observed wide range of OCB prevalence [24,[26][27][28][29]33,[42][43][44]47,48,55,56,[68][69][70][71][72][73][74][75]…”

“…Nevertheless, it has to be considered that some studies only included OCB-positive MS patients while other studies comprised a certain percentage of OCB-negative MS patients, thus leading the observed wide range of OCB prevalence [24,[26][27][28][29]33,[42][43][44]47,48,55,56,[68][69][70][71][72][73][74][75]92]. KFLC measurements, interpreted by different approaches, reached a mean diagnostic sensitivity of 94% (min-max: 72-100%) and specificity of 84% (min-max: 65-100%) in MS patients [24,[26][27][28][29]33,[42][43][44]47,48,55,56,[68][69][70][71][72][73][74][75]92]. Patients with CIS, including patients with and without the later diagnosis of MS during follow up revealed an OCB prevalence of 78% (25-100%) [24,[26]…”