Diagnostic value of immunoglobulin free light chains at the debut of multiple sclerosis

Abstract

The use of free light chains as a laboratory marker can increase the accuracy of MS diagnosis. These markers can help indirectly assess the risk of transformation of a clinically isolated syndrome into definite multiple sclerosis within the first 2 years of disease.

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

“…In contrast, other studies denied a correlation between disease progression evaluated by EDSS and KFLC CSF concentration or KFLC indices [43,66,69,77,84,87]. In some studies, high KFLC CSF concentrations or KFLC indices were associated with a higher risk for CIS patients to be later diagnosed with definite MS [43,50,53,54,61,68,69,73,82,83,86,130]. In other studies, this correlation could not have been observed, and CIS patients with conversion to MS did not reveal elevated CSF KFLC [55,84,87].…”

“…Some studies, which investigated the utility of FLC measurement in the diagnosis of MS, empirically created cut-off values either for the absolute KFLC or LFLC concentrations in CSF, CSF/serum KFLC, and LFLC quotients (Q KFLC , Q LFLC ), CSF KFLC/IgG, and LFLC/IgG ratios or KFLC/LFLC concentration ratios to determine KFLC or LFLC positivity [4,19,20,23,33,47,48,50,[52][53][54][55][60][61][62][63][64][65][66][67][68]73,74,76,77,85,[88][89][90][91]130]. The cut-off for the CSF KFLC concentration varied between 0.103 µg/mL and 7 mg/L and a mean diagnostic sensitivity and specificity of 86% (95% confidence interval (80%, 92%)) and 91% (86%, 96%) was reached while the threshold for CSF LFLC concentration varied between 0.0175 µg/mL and 4.3 mg/L and a mean sensitivity and specificity of 67% (48%, 85%) and 82% (67%, 96%) was reported [4,19,20,23,33,47,48,50,[52][53][54][55][60]…”

“…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.…”

Cerebrospinal Fluid Analysis in Multiple Sclerosis Diagnosis: An Update

“…Recently, Nazarov, V. et al showed an association between kFLC and the degree of irreversible disability in MS patients. In particular, the authors showed that MS patients with high levels of kFLC reached disability faster than patients who had low kFLC levels, suggesting that it can be a good prognostic marker in MS [44,45]. Goffette et al studied 33 patients with clinically suspected MS and no detectable OCB and reported that 54% of them were positive for kFLC.…”