Cerebrospinal fluid oligoclonal IgM test in routine practice: Comparison with quantitative assessment of intrathecal IgM synthesis

Zeman, David; Kušnierová, Pavlína; Všianský, František; Reguliová, Katarína; Škutová, Monika; Woznicova, Ivana; Zapletalová, Olga; Hradílek, Pavel

doi:10.1016/j.cca.2020.05.021

Cited by 6 publications

(8 citation statements)

References 35 publications

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“…A major debate regards the best method for detecting the ITMS. A recent study confirmed that the quantitative method described by Reiber is specific (97.6%) but with low sensitivity (23%) compared to qualitative detection [27]. Our analysis confirms this finding, as the prevalence of ITMS was consistently higher when detected with qualitative methods (OCMBs or LS-OCMBs).…”

Section: Discussionsupporting

confidence: 87%

“…The prevalence of IgG OCBs was lower in CIS than in RRMS (80.5% versus 91.0%, p < 0.05). We excluded the studies that referred to the 2017 revision of McDonald criteria [ 8 , 27 , 33 , 34 , 35 , 36 ] as sensitivity analyses. The results did not change (CIS versus RRMS patients, 23.9% 338/1412 vs. 42.3% 412/973, p < 0.00001).…”

Section: Resultsmentioning

confidence: 99%

“…The pH range required for IEF of IgM ranges from 5 to 8 (instead of the pH = 3–10 required for IgG [ 27 ]), and the circulating IgM pentamers can migrate through the gel on IEF only after they have been reduced, with the risk of arbitrary reassociation and false-positive and -negative results [ 46 ]. Moreover, the cut-off normally used is the presence of two or more bands in the CSF not present in the paired serum sample [ 26 ], but a four-band cut-off has also been proposed [ 27 ]. Despite these limitations, semi-automated methods have been developed and could be included in clinical practice in the future [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…Very briefly, technical difficulties arose since IgM concentration in the CSF is 200 times less than IgG, immunoglobulins M are hydrophobic, and in vivo are aggregated in pentameric structure [ 22 , 25 ]. Notwithstanding, different groups demonstrated good interlaboratory reproducibility in the last years, suggesting different methods for introducing OCMBs in clinical practice [ 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal Fluid IgM and Oligoclonal IgG Bands in Multiple Sclerosis: A Meta-Analysis of Prevalence and Prognosis

et al. 2021

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The presence of intrathecal IgM synthesis (ITMS) has been associated with an aggressive multiple sclerosis (MS) clinical course. In the present systematic review, we aimed at assessing the prevalence of ITMS among different MS phenotypes. Moreover, we aimed at quantifying the risk of a second relapse in ITMS positive and oligoclonal IgG bands (OCGBs)-positive patients. We selected clinical studies reporting the ITMS prevalence assessed as oligoclonal IgM Bands (OCMBs), lipid-specific OCMBs (LS-OCMBs), and/or as an intrathecal IgM production > 0% (IgMLoc, Reiber formula). The overall prevalence of ITMS was higher in relapsing-remitting (RR) than clinically isolated syndrome (CIS) patients (40.1% versus 23.8%, p < 0.00001), while was in line with that detected in primary progressive MS (PPMS, 26.7%). Almost all patients (98%) with ITMS had also OCGBs. The risk of having a second relapse was higher in OCGBs positive patients (HR = 2.18, p = 0.007) but much higher in ITMS positive patients (HR = 3.62, p = 0.0005). This study revealed that the prevalence of ITMS is higher in RRMS patients. It suggests that the risk of having a second relapse, previously ascribed to OCGBs, may, to a certain extent, be related to the presence of intrathecal IgM.

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Section: Discussionsupporting

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal Fluid IgM and Oligoclonal IgG Bands in Multiple Sclerosis: A Meta-Analysis of Prevalence and Prognosis

et al. 2021

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“…In this study, LS-OCMB showed a greater value than Reibergram, and this difference might probably be explained by the already reported lower sensitivity of Reibergram compared with OCMB. 47,48 A positive Reibergram has strongly been associated with worse outcomes, 21,[26][27][28] but their higher percentage of falsenegative results compared with OCMB may diminish its utility. 48 Compared with OCMB, LS-OCMB may identify more accurately those patients at a higher risk of early disability by the fact that OCMB might be due to transient immune activation while LS-OCMB a sustained IgM response associated with CD5 + B cells.…”

Section: Discussionmentioning

confidence: 99%

Predicting Aggressive Multiple Sclerosis With Intrathecal IgM Synthesis Among Patients With a Clinically Isolated Syndrome

Monreal

Maza

Costa‐Frossard

et al. 2021

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo 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).MethodsProspective 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).ResultsA 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).ConclusionsITMS predicts an aggressive MS at disease onset, especially when detected as LS-OCMB.Classification of EvidenceThis 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.

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Prognostic value of intrathecal IgM synthesis determined by various laboratory methods in patients with early multiple sclerosis - a prospective observational study

Revendová

Zeman

Kušnierová

et al. 2022

Multiple Sclerosis and Related Disorders

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Cerebrospinal fluid oligoclonal IgM test in routine practice: Comparison with quantitative assessment of intrathecal IgM synthesis

Cited by 6 publications

References 35 publications

Cerebrospinal Fluid IgM and Oligoclonal IgG Bands in Multiple Sclerosis: A Meta-Analysis of Prevalence and Prognosis

Cerebrospinal Fluid IgM and Oligoclonal IgG Bands in Multiple Sclerosis: A Meta-Analysis of Prevalence and Prognosis

Predicting Aggressive Multiple Sclerosis With Intrathecal IgM Synthesis Among Patients With a Clinically Isolated Syndrome

Prognostic value of intrathecal IgM synthesis determined by various laboratory methods in patients with early multiple sclerosis - a prospective observational study

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