The diagnostic value of IgG index versus oligoclonal bands in cerebrospinal fluid of patients with multiple sclerosis

Abstract

Background Diagnostic criteria for multiple sclerosis have been developed to guide the diagnostic process. In the latest revision of the McDonald criteria, the presence of oligoclonal bands may replace the need for dissemination in time. The aim of this study is to investigate if the less time-consuming analysis of immunoglobulin G index in cerebrospinal fluid can safely predict the findings of oligoclonal bands. Methods This is a retrospective study of patients with multiple sclerosis at three hospitals in South-East Norway where lumbar puncture is performed routinely. We included patients diagnosed with multiple sclerosis after 2005 with known oligoclonal band status and an immunoglobulin G index score. Results Of 1295 patients diagnosed during or after 2005, 93.8% were oligoclonal band positive at diagnosis. Of 842 multiple sclerosis patients with known immunoglobulin G index and oligoclonal band status, 93.3% were oligoclonal band positive and 76.7% had an elevated immunoglobulin G index. The positive predictive value of a high immunoglobulin G index when oligoclonal bands are positive was 99.4% (95% confidence interval 98.4–99.8%). The negative predictive value of a normal immunoglobulin G index when oligoclonal bands are negative was 26.5% (95% confidence interval 23.5–29.9%). Conclusion An immunoglobulin G index >0.7 has a positive predictive value >99% for oligoclonal bands. An elevated immunoglobulin G index adds diagnostic value versus oligoclonal bands and saves time in the diagnostic process.

IgG Index Revisited: Diagnostic Utility and Prognostic Value in Multiple Sclerosis

“…In our study, IgG index and OCB are highly correlated, with IgG index > 0.7 highly suggestive of OCB positivity (PPV: 86.4%, PLR 4.57). In previous studies in the Caucasian population, the correlation can be more significant with a PPV even reaching 99% with a cutoff of 0.7 and 96% with a cutoff of 0.8 (7,8,33). It should also be noted that IgG index ≤0.7 may not exclude a negative OCB (NPV: 62.3%, NLR 0.44), in line with previous studies (7,33).…”

“…In previous studies in the Caucasian population, the correlation can be more significant with a PPV even reaching 99% with a cutoff of 0.7 and 96% with a cutoff of 0.8 (7,8,33). It should also be noted that IgG index ≤0.7 may not exclude a negative OCB (NPV: 62.3%, NLR 0.44), in line with previous studies (7,33). This might be attributed to the inherent low sensitivity (52%) of the test given its methodology.…”

“…As a routinely performed workup for patients suspected of MS, IgG index is a reachable and cost-effective candidate as evidence of DIT (1). Its diagnostic and prognostic value yet lacks real-world evidence from Asian countries, where OCB result is often lacking at initial presentation, impeding an early diagnosis of MS (7,(28)(29)(30). In a cohort of CIS patients in China, we found that [1] IgG index > 0.7 is highly suggestive of OCB positivity; [2] IgG index has a higher specificity and PPV than OCB for MS diagnosis, and is indicative of early disease activity; [3] When OCB result is lacking at baseline, IgG index serves as a specific surrogate of OCB in the 2017 McDonald criteria; when OCB result is available, IgG index and OCB double-positivity strongly suggests the diagnosis of MS; whereas IgG index/OCB positivity facilitates the MS diagnosis without impairing the diagnostic performance.…”

“…Given its low cost and easy accessibility, IgG index is still considered a potential candidate for MS diagnosis despite a relatively low sensitivity (50-75% among MS patients) (3). Studies on its specificity, however, generated mixing results (7)(8)(9)(10). Furthermore, the prognostic value of IgG index or OCB remains undetermined based on existing evidence (10)(11)(12)(13).…”

Epstein-Barr Virus and Multiple Sclerosis

“…Diagnosis of MS relies on the so-called McDonald criteria, latest updated in 2017 (5). These criteria include detection of active inflammatory foci in the CNS as seen by positron emission tomography (PET) and magnetic resonance imaging (MRI) and intrathecal production of immunoglobulins (Igs), measured as an elevated cerebrospinal fluid (CSF)/serum IgG index, as a free light chain index or as the occurrence of oligoclonal bands (OCBs) of IgG in CSF (6)(7)(8)(9)(10). Each oligoclonal band is a result of intrathecal antibody (Ab) synthesis by single B cell clones and therefore, specific CSF/ serum Ab indices (AIs) may also be elevated, e.g., Abs to various viruses, corresponding to the specificity of some of the OCBs (11)(12)(13)(14)(15).…”