Indirect Immunofluorescence May Aid in Detecting Anti-MOG Antibodies in NMOSD, MOGAD

Sushil Kumar, MD, MBBS

A 2024 case study of 5 patients with neuromyelitis optica spectrum disorder (NMOSD) showed that serum anti-MOG antibody positivity was observed through indirect immunofluorescence (IIF), but not through cerebrospinal fluid (CSF). All told, investigators concluded that IIF may be a useful tool for quickly identifying anti-MOG antibodies (Abs) in NMOSD.

Prior to this study, recent research found that some patients with NMOSD have negative anti-aquaporin-4 (AQP4) Abs but positive anti-MOG Abs. This provided information on a specific illness called “MOG-encephalitis (EM).” Led by Sushil Kumar, MD, MBBS, an associate professor at the AIIMS in Bihar, India, this latest study featured 5 NMOSD cases with serum anti-MOG antibody positivity was detected via IIF, none of which showed CSF positivity or anti-AQP antibodies.

Case 1:

A 22-year-old man presented with bilateral limb weakness, occipital headache, and decreased facial sensation. CSF analysis ruled out infection, while MRI showed plaque-like T2/FLAIR hyperintensities in the left middle cerebellar peduncle and right ventral midbrain, suggestive of demyelination. Serum testing detected MOG antibodies (AQP-4 negative), but CSF was negative for both antibodies and oligoclonal bands. He was treated with rituximab at 1 g every 15 days for six months, with favorable clinical progress.

Case 2:

An 8-year-old girl developed acute vision loss in her left eye following a headache, vomiting, urinary retention, and significant weight loss. Examination revealed retinal nerve fiber layer edema, disc hyperemia, and a Grade 1 relative afferent pupillary defect in the left eye. Brain MRI showed multifocal T2/FLAIR hyperintensities in subcortical and deep white matter, with findings consistent with optic neuritis and acute demyelination. Serum testing was positive for anti-MOG antibodies. She was treated with prednisolone for three months, followed by a gradual taper, resulting in clinical improvement.

Case 3:

A 15-year-old girl presented with progressive lower limb stiffness, muscle weakness, and a one-year history of a burning sensation in her lower extremities. She also reported a prior episode of abrupt vision loss. MRI of the brain and spine revealed features consistent with NMOSD, and serum testing was positive for MOG antibodies. CSF studies were unremarkable. Treatment included oral azathioprine (40 mg), gabapentin, nortriptyline, and prednisolone tapered over several weeks. She showed gradual improvement in motor and sensory symptoms.

Case 4:

A 14-year-old boy was admitted with fever, bilateral lower limb weakness, inability to sit or stand, and urine retention lasting one day. He also reported slurred speech and two episodes of vomiting. MRI findings were consistent with an inflammatory demyelinating process. The patient was treated with prednisolone tablets, initially 15 mg daily, tapered to 10 mg. Symptoms improved, and urinary retention resolved following catheterization. There was no history of rash, chills, or contact with tuberculosis.

Case 5:

An 11-year-old girl presented with gradual vision loss in her right eye over five days, starting with blurriness and progressing to complete blindness. Examination confirmed right eye optic neuritis without involvement of the left eye. MRI findings supported a diagnosis of transverse myelitis and paraplegia. There was no history of fever, seizures, or infectious exposure. She was started on prednisolone (40 mg tapered to 30 mg) with plans to introduce azathioprine for long-term immunosuppression.

READ MORE: Oligoclonal Bands in Cerebrospinal Fluid May Signal Higher Relapse Risk in MOGAD

In the study, cases 3 and 4 received new NMOSD diagnoses, while the other patients had prior histories and returned with acute episodes. These findings underscored the utility of IIF for identifying anti-MOG antibodies in NMOSD, particularly as MOG antibody-associated (MOGAD) gain prominence.

Historically, NMOSD was thought to be more prevalent than MOGAD in adults with inflammatory demyelinating diseases, while MOGAD was seen more commonly in children. However, recent research indicates that MOGAD cases may now surpass NMOSD, even in adult populations across both Asian and non-Asian groups. This shift likely reflects an increased understanding of MOGAD and the growing availability of advanced diagnostic techniques, such as cell-based assays, which allow for more precise detection of anti-MOG antibodies. These developments emphasize the importance of continued advancements in neuroimmunology and the need for broader diagnostic accessibility to better distinguish between NMOSD and MOGAD in clinical practice.

REFERENCE
1. Datta D, Mahto S, Sinha U, Kumar S. Indirect Immunofluorescence-Aided Detection of Antimyelin Oligodendrocyte Glycoprotein Antibodies in Neuromyelitis Optica Spectrum Disorder/Myelin Oligodendrocyte Glycoprotein-Associated Antibody Disorder: A Case Series Involving Five Patients. Annals of African Med. 2024;23(4):731-736. doi: 10.4103/aam.aam_37_24