ABSTRACT
BACKGROUND: HTLV1-associated myelitis (HAM) is a slowly progressive myelopathy in which spinal cord MRI demonstrates no lesion or atrophy. OBJECTIVE: We examined the overlap between NMOSD features and HTLV1 infection. METHODS: We included all HTLV1-infected patients recruited in French West Indies (FWI) or referred from different centers, and suffering from at least one NMOSD feature. Literature connecting HTLV1-infection and NMOSD was reviewed. RESULTS: We included six NMOSD-like HAM with acute onset, seronegative against AQP4 and MOG-Abs. All displayed extensive longitudinal myelitis, and the optic nerve was involved in three. We gathered 39 cases of NMOSD-like HAM patients from the literature. Atypical signs of HAM were relapses (15.4%), sensory level (50%), upper limb symptoms (35.9%), optic neuritis (10.2%). Typical lesions involved lateral funiculi and featured a double rope sign (56.3%). CONCLUSION: We propose that acute onset of NMOSD-like HAM could be more frequent than expected and should be evoked in high-risk patients. Extensive but often transient cord lesions could be the hallmark of an excessive inflammation of the funiculi targeted by HTLV1 infection. Although usually minor, a few HAM cases demonstrate specific MRI lesions, and the most severe cases may mimic NMOSD attacks.
Subject(s)
Antineoplastic Agents/adverse effects , Brentuximab Vedotin/adverse effects , Guillain-Barre Syndrome/chemically induced , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/chemically induced , Adult , Aged , Antineoplastic Agents/therapeutic use , Brentuximab Vedotin/therapeutic use , Female , Hodgkin Disease/drug therapy , Humans , Lymphoma, Non-Hodgkin/drug therapy , Male , Middle Aged , Young AdultABSTRACT
In MS, B cells survive peripheral tolerance checkpoints to mediate local inflammation, but the underlying molecular mechanisms are relatively underexplored. In mice, the MIF pathway controls B-cell development and the induction of EAE. Here, we found that MIF and MIF receptor CD74 are downregulated, while MIF receptor CXCR4 is upregulated in B cells from early onset MS patients. B cells were identified as the main immune subset in blood expressing MIF. Blocking of MIF and CD74 signaling in B cells triggered CXCR4 expression, and vice versa, with separate effects on their proinflammatory activity, proliferation, and sensitivity to Fas-mediated apoptosis. This study reveals a new reciprocal negative regulation loop between CD74 and CXCR4 in human B cells. The disturbance of this loop during MS onset provides further insights into how pathogenic B cells survive peripheral tolerance checkpoints to mediate disease activity in MS.