Case report: Concurrent MOG antibody-associated disease and latent infections in two patients

Abstract

Objectives: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is frequently preceded by infections. The underlying pathomechanism, however, remains poorly understood. Here, we present the clinical data of two MOGAD patients with concurrent syphilis infection and investigate the reactivity of patient-derived antibodies to MOG and Treponema pallidum (T. pallidum).

Methods: Longitudinal serum samples and soluble immunoglobulins in single B cell supernatants were measured for MOG reactivity by a live cell-based assay. Reactivity against T. pallidum was assessed by enzyme-linked immunosorbent assay.

Results: The two patients presented MOGAD and concurrent latent syphilis infection, manifesting as cervical myelitis and unilateral optic neuritis, respectively. The first patient had been living with HIV on antiretroviral therapy, and the second was concomitantly diagnosed with chronic hepatitis B infection. Upon screening of B cell supernatants, we identified reactivity to MOG or T. pallidum. Notably, one B cell showed reactivity to both antigens.

Discussion: The coexistence of MOGAD diagnoses and latent syphilis, alongside the identification of antibody reactivity to MOG and T. pallidum, underscores the potential pathomechanistic link between syphilis infection and subsequent autoimmune neuroinflammation. Cross-reactivity between MOG and T. pallidum antibodies remains to be validated on a molecular level, and further characterization of infectious triggers associated with MOGAD is needed.

Keywords: B cells; antibodies; case report; infection; molecular mimicry; myelin oligodendrocyte glycoprotein; myelin oligodendrocyte glycoprotein antibody-associated disease; syphilis.

Figure 1

Clinical features at baseline and follow-up. Case 1: (A) Spinal MRI with sagittal T1 showing contrast-enhancing lesion on the level of cervical vertebrae 4/5, presenting as numbness in the genital area and both legs. (B) Cerebral MRI with transversal FLAIR revealing a new lesion in the left brainstem 6 months after initial treatment with IVIG. (C) Longitudinal MOG-IgG values (geometric MFI ratio). The dotted line indicates the cutoff for clear-positive MOG-IgG signals (geometric MFI ratio = 3). The square indicates treatment with an antibiotic (intravenous penicillin [20 million units/day] for 14 days) and the triangle indicates IVIG treatment (150 g over 5 days). Case 2: (D) Transversal T1 showing contrast enhancement of the right optic nerve at diagnosis. OCT showing slightly (yellow) and severely (red) diminished pRNFL thickness of the right eye. (E) Transversal post-contrast T1 showing bilateral normal optic nerves; however, OCT showed a decrease of the pRNFL thickness of the right eye 8 months after initial treatment with methylprednisolone. (F) MOG-IgG values (geometric MFI ratio) at baseline and follow-up time points. Cutoff for clear-positive MOG-IgG signals (geometric MFI ratio = 3) indicated as a dotted line. The square indicates treatment with an antibiotic (benzathine penicillin [2.4 million U/week] over 3 weeks) and the triangle indicates treatment with glucocorticoids (methylprednisolone 3 g over 3 days). MRI, magnetic resonance imaging; FLAIR, fluid-attenuated inversion recovery; IVIG, intravenous immunoglobulin; MOG, myelin oligodendrocyte glycoprotein; MFI, mean fluorescence intensity; OCT, optical coherence tomography; pRNFL, peripapillary retinal nerve fiber layer.

Figure 2

Experimental design. Schematic illustration of the experimental setup and the number of isolated B cell supernatants with detected reactivities to MOG and T. pallidum. MOG, myelin oligodendrocyte glycoprotein; T. pallidum, Treponema pallidum; PBMCs, peripheral blood mononuclear cells.