What are oligoclonal bands?

What Are Oligoclonal Bands?

Oligoclonal bands (OCBs) are discrete populations of immunoglobulin G (IgG) antibodies detected in cerebrospinal fluid (CSF) that represent intrathecal (within the central nervous system) antibody synthesis, serving as a key immunological marker of inflammatory CNS disease, particularly multiple sclerosis. 1

Technical Definition and Detection

• OCBs are identified through isoelectric focusing on agarose gel followed by immunodetection, which is the gold standard technique for their determination 2
• They appear as distinct bands of IgG (and sometimes IgM) immunoglobulins that are present in CSF but absent or different from corresponding serum samples 1
• The test requires only 50 microliters of unconcentrated CSF using modern micromethod techniques 3
• Five distinct OCB patterns exist, with patterns 2 and 3 (CSF-restricted bands) being most clinically significant for inflammatory CNS disease 1

Clinical Significance in Multiple Sclerosis

OCBs are present in 95-98% of MS patients in Central and Northern Europe, making them a cornerstone diagnostic finding, though their frequency varies by geographic region and ethnicity. 1, 3

• In MS diagnostic criteria, positive CSF is defined by oligoclonal bands detected by established methods (preferably isoelectric focusing) that are different from any bands in serum, or by a raised IgG index 1
• The presence of OCBs can substitute for MRI dissemination in space when combined with at least two MRI-detected lesions consistent with MS 1
• Geographic variation is important: OCB frequency may be lower in Asian MS patients (40-80% in Japan) and some European regions like Sardinia (84%) 1

Differential Diagnosis Considerations

While highly associated with MS, OCBs are not specific to this condition and appear in various other neurological diseases, requiring careful clinical correlation. 3

• OCBs are detected in 90% of subacute sclerosing panencephalitis cases and 100% of herpes simplex encephalitis cases 3
• They appear less frequently in other CNS infections, and are found in some patients with Alzheimer disease, cerebrovascular accidents, and CNS gliomas 3
• OCBs are typically absent in Parkinson disease, Huntington disease, Creutzfeldt-Jakob disease, and herniated disc disease 3

Distinguishing MS from MOG Encephalomyelitis

OCBs are present in only 12-13% of MOG encephalomyelitis (MOG-EM) patients, making their absence a useful distinguishing feature from MS. 1

• Many MOG-EM patients previously misdiagnosed with MS were atypical in lacking OCBs 1
• However, positive OCBs do NOT exclude MOG-EM, as they can occasionally be present 1
• The absence of CSF-restricted OCBs (patterns 1,4, or 5) is more characteristic of MOG-EM than MS 1

Special Clinical Scenarios

• A single abnormal IgG band confined to CSF (without oligoclonal pattern) occurs in only 0.55% of samples and may suggest diseases other than MS, or mark an aggressive MS course with prominent affective disorder 4
• In autoimmune encephalitis (NMDA-receptor, VGKC-complex antibodies), CSF frequently shows lymphocytosis and elevated protein, with oligoclonal bands present in some cases 1
• OCBs can be detected in immune checkpoint inhibitor-related encephalitis, where their presence may indicate need for more aggressive immunosuppression 1

Pathophysiological Implications

• The target specificities of OCB antibodies in MS remain largely unknown, though recent evidence suggests they may target patient-specific peptides with homologies to viral proteins and proteins involved in cell stress and apoptosis 5
• OCBs represent IgG1 and IgG3 subclass antibodies, indicating an active immune response 5
• The distinct sets of oligoclonal IgG-reactive peptides identified in individual MS patients suggest patient-specific rather than universal antigenic targets 5

Clinical Pitfalls to Avoid

• Do not diagnose MS based solely on OCB presence without meeting full diagnostic criteria, as OCBs appear in multiple inflammatory conditions 1, 3
• Do not assume OCB-negative patients cannot have MS, particularly in Asian populations or younger patients where frequency may be lower 1
• In MOG-EM, do not exclude the diagnosis based on OCB presence alone, as occasional patients can be OCB-positive 1, 6
• Ensure CSF analysis quality is adequate, as poor laboratory technique can yield unreliable results 1