Cieľ: Voľné ľahké reťazce kappa (kappa free light chains; k-fLC) v likvore sú perspektívnym novým markerom intratekálnej syntézy imunoglobulínov (Ig) u pacientov s RS, pričom publikované referenčné hodnoty nie sú jednotné. Cieľom našej práce bolo analyzovať diagnostickú hodnotu k-fLC (hladiny v likvore, kvocientu, indexu) a rutinne vyšetrovaných markerov (IgG index, IgGReiber) v diagnostike RS, v predikcii pozitivity oligoklonálnej skladby (oligoclonal bands; OCB) a u OCB negatívnych pacientov. Metódy: Párované vzorky séra a likvoru boli analyzované v súbore 46 pacientov s RS a 63 kontrolných jedincov s nezápalovými a inými zápalovými ochoreniami CNS. Koncentrácia k-fLC bola meraná imunoturbidimetricky (SPA PLUS®, Freelite®). Pre jednotlivé markery a ich cut-off hodnoty, určené s použitím Youdenovho indexu, boli porovnané ROC krivky, diagnostické senzitivity a špecificity. Výsledky: Optimálne cut-off hodnoty boli: 0,76 pre IgG index; 0,89 mg/l pre IgGReiber; 1,08 mg/l pre hladinu k-fLC v likvore; 0,0994 pre k-fLC kvocient; 18,15 pre k-fLC index. K odlíšeniu RS od control boli zistené najvyššie kombinované diagnostické senzitivity/špecificity pre k-fLC index (0,76/0,98), nasledované k-fLC kvocientom (0,76/0,97), hladinou k-fLC v likvore (0,76/0,95), intratekálnou syntézou IgGReiber (0,70/0,91) a IgG indexom (0,65/0,89). Senzitivita a špecificita OCB vyšetrenia bola 0,83 a 1,00. V predikcii OCB pozitivity malo použitie nových k-fLC markerov excelentnú diagnostickú využiteľnosť so senzitivitou/špecificitou: 0,92/0,99 pre k-fLC index; 0,92/0,97 pre k-fLC kvocient; 0,92/0,96 pre hladinu k-fLC v likvore, v porovnaní s 0,76/0,89 pre IgG index a 0,76/0,86 pre IgGReiber. U OCB negatívnych RS pacientov s použitím navrhnutých cut-off bola najvyššia diagnostická senzitivita (0,38) detekovaná pre IgGReiber, nasledovaná senzitivitou 0,13 pre IgG index a prekvapivo 0,00 senzitiviou pre k-fLC markery. Záver: V diagnostike RS a pri predikcii OCB pozitivity sme detekovali pre všetky analyzované k-fLC markery lepšie diagnostické senzitivity a špecificity v porovnaní s rutinne používaným IgG indexom a IgGReiber, tieto však nedosiahli senzitivitu a špecificitu OCB vyšetrenia. Pre dôkaz intratekálnej syntézy Ig u pacientov so suspektnou RS odporúčame paralelné vyšetrenie OCB spolu s použitím k-fLC indexu a kvocientu, a to predovšetkým ak OCB nález je nejednoznačný alebo negatívny.

Aim: Kappa free light chains (-fLC) in cerebrospinal fl uid (CSF) were suggested as promising novel markers of intrathecal immunoglobulin (Ig) synthesis in MS patients, with reported discrepant reference values. We aimed to analyse the diagnostic accuracy of k-fLC (CSF concentration, quotient, index) and routinely used markers (IgG index, IgGReiber) in MS diagnostics, in prediction of oligoclonal bands (OCB) positivity and in OCB negative patients. Methods: Serum/CSF paired samples were analysed from 46 MS patients and 63 controls with non-inflammatory and non-MS inflammatory diseases of CNS. The concentrations of k-fLC were measured immunoturbidimetrically (SPA PLUS®, Freelite®). The ROC curves, diagnostic sensitivities and specificities were analysed with respect to the cut-offs, which were determined using Youden’s index. Results: The optimal cut-off values were defined as: 0.76 for IgG index; 0.89 mg/L for IgGReiber; 1.08 mg/L for CSF k-fLC level; 0.0994 for k-fLC quotient; 18.15 for k-fLC index. To distinguish MS patients from controls, the highest combined sensitivities/specificities were observed for k-fLC index (0.76/0.98), followed by k-fLC quotient (0.76/0.97), CSF k-fLC level (0.76/0.95), IgGReiber (0.70/0.91) and IgG index (0.65/0.89). The OCB detection showed the sensitivity 0.83 and the specificity 1.00. In prediction of OCB positivity, the novel k-fLC markers showed excellent diagnostic accuracy with sensitivities/specificities: 0.92/0.99 for k-fLC index, 0.92/0.97 for k-fLC quotient, and 0.92/0.96 for CSF k-fLC level, compared to 0.76/0.89 for IgG index and 0.76/0.86 for IgGReiber. Applying our cut-offs in OCB negative MS patients, the highest diagnostic sensitivity (0.38) was found for IgGReiber, followed by 0.13 for IgG index, and surprisingly by 0.00 for all k-fLC markers. Conclusion: In MS diagnostics and in prediction of OCB positivity, all novel k-fLC markers showed better sensitivities and specificities than routinely used IgG index and IgGReiber, but did not reach those of OCBs. To proove the intrathecal Ig synthesis in patients with suspected MS, we recommend to use k-fLC index and quotient along with OCB, especially if OCB findings are equivocal or negative.

Clinic of Neurology Jessenius Faculty of Medicine in Martin Comenius University in Bratislava and University Hospital Martin

Department of Clinical Biochemistry Jessenius Faculty of Medicine in Martin Comenius University in Bratislava and University Hospital Martin

Department of Medical Biochemistry and BioMed Jessenius Faculty of Medicine in Martin Comenius University in Bratislava

Department of Molecular Medicine Biomedical Center Martin Jessenius Faculty of Medicine in Martin Comenius University in Bratislava

Voľné ľahké reťazce kappa pri roztrúsenej skleróze - diagnostická hodnota a porovnanie s ďalšími markermi

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