B cell depletion can be effective in multiple sclerosis but failed in a patient with advanced childhood cerebral X-linked adrenoleukodystrophy

Abstract

Rituximab exerts its clinical efficacy by its specific pattern of depletion of CD20⁺ B lymphocytes and it has been demonstrated that rituximab is an effective treatment for relapsing remitting multiple sclerosis. X-linked adrenoleukodystrophy (X-ALD), the most common monogenetic neuroinflammatory disorder, shares substantial overlap with multiple sclerosis in the neuropathological changes found in brain tissues in advanced stages of the disease. While there is no effective therapy for these patients, we hypothesized that rituximab might be effective in arresting the neuroinflammatory process. Our detailed clinical, imaging and immunological data revealed that rituximab is not effective in advanced stages of X-ALD and consequently should not be applied for compassionate use in these patients.

Keywords: B cells; X-ALD; X-linked adrenoleukodystrophy; multiple sclerosis; rituximab.

Figure 1.

Magnetic resonance imaging (MRI) data. (a) Initial Cerebral MRI (cMRI) before rituximab treatment: symmetric hyperintense T2 FLAIR signal in the parieto-occipital white matter (age 7 years, 10 months; Philips 1.5T T2 FLAIR axial). (b) Last cMRI 4 months after rituximab treatment: symmetric hyperintense T2 FLAIR signal in the parieto-occipital white matter with progression of inflammatory demyelination extending to the frontal lobe (age 8 years, 3 months; SIEMENS 1.5T T2 FLAIR axial). (c) Initial cMRI before rituximab treatment: symmetric hypointense T1 signal in the parieto-occipital region with contrast enhancement at the advancing margin (age 7 years, 10 months; Philips 1.5T T1 post gadolinium axial). (d) Last cMRI 4 months after rituximab treatment: symmetric hypointense T1 signal in the parieto-occipital region with contrast enhancement at the advancing margin extending to the frontal lobe (age 8 years, 3 months; SIEMENS 1.5T T1 post gadolinium axial).

Figure 2.

Analysis of peripheral immune cell subtypes: peripheral blood immune cell subtypes including CD19⁺ B cells and CD3⁺ T cells were evaluated prior to the first, second, third and fourth as well as after the fourth rituximab infusion. Normal percentages of CD19⁺ B cells and CD3⁺ T before the first rituximab infusion. CD19⁺ B cells decreased markedly after the first rituximab cycle, with further reduction to zero after the fourth rituximab infusion.