PT  - JOURNAL ARTICLE
AU  - Monreal, Enric
AU  - Sainz de la Maza, Susana
AU  - Costa-Frossard, Lucienne
AU  - Walo-Delgado, Paulette
AU  - Zamora, Javier
AU  - Fernández-Velasco, José Ignacio
AU  - Villarrubia, Noelia
AU  - Espiño, Mercedes
AU  - Lourido, Daniel
AU  - Lapuente, Paloma
AU  - Toboso, Inmaculada
AU  - Álvarez-Cermeño, José Carlos
AU  - Masjuan, Jaime
AU  - Villar, Luisa María
TI  - Predicting Aggressive Multiple Sclerosis With Intrathecal IgM Synthesis Among Patients With a Clinically Isolated Syndrome
AID  - 10.1212/NXI.0000000000001047
DP  - 2021 Sep 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e1047
VI  - 8
IP  - 5
4099  - http://nn.neurology.org/content/8/5/e1047.short
4100  - http://nn.neurology.org/content/8/5/e1047.full
SO  - Neurol Neuroimmunol Neuroinflamm2021 Sep 01; 8
AB  - Objective To determine the best method to measure intrathecal immunoglobulin (Ig) M synthesis (ITMS), a biomarker of worse prognosis in multiple sclerosis (MS). We compared the ability for predicting a poor evolution of 4 methods assessing ITMS (IgM oligoclonal bands [OCMBs], lipid-specific OCMBs [LS-OCMBs], Reibergram, and IgM index) in patients with a clinically isolated syndrome (CIS).Methods Prospective study with consecutive patients performed at a referral MS center. We used unadjusted and multivariate Cox regressions for predicting a second relapse, Expanded Disability Status Scale (EDSS) scores of 4 and 6, and development of secondary progressive MS (SPMS).Results A total of 193 patients were included, with a median (interquartile range) age of 31 (25–38) years and a median follow-up of 12.9 years. Among all methods, only OCMB, LS-OCMB, and Reibergram significantly identified patients at risk of some of the pre-established outcomes, being LS-OCMB the technique with the strongest associations. Adjusted hazard ratio (aHR) of LS-OCMB for predicting a second relapse was 2.50 (95% CI 1.72–3.64, p < 0.001). The risk of reaching EDSS scores of 4 and 6 and SPMS was significantly higher among patients with LS-OCMB (aHR 2.96, 95% CI 1.54–5.71, p = 0.001; aHR 4.96, 95% CI 2.22–11.07, p < 0.001; and aHR 2.31, 95% CI 1.08–4.93, p = 0.03, respectively).Conclusions ITMS predicts an aggressive MS at disease onset, especially when detected as LS-OCMB.Classification of Evidence This study provides Class II evidence that lipid-specific IgM oligoclonal bands can predict progression from CIS to MS and a worse disease course over a follow-up of at least 2 years.aHR=adjusted hazard ratio; CIS=clinically isolated syndrome; DMT=disease-modifying treatment; EDSS=Expanded Disability Status Scale; FN=false negative; FP=false positive; HRC=Hospital Universitario Ramón y Cajal; Ig=immunoglobulin; ITMS=intrathecal IgM synthesis; LS-OCMB=lipid-specific IgM oligoclonal band; MS=multiple sclerosis; NPV=negative predictive value; OCMB=IgM oligoclonal band; PPV=positive predictive value; RRMS=relapsing-remitting MS; SPMS=secondary progressive MS; TN=true negative; TP=true positive