Table 3.
Pending questions.
| *Does intrathecal IgM synthesis occur during HIV infection? |
| *Is intrathecal IgG synthesis suppressed during long-term CSF HIV eradication (confirmed with ultra-sensitive PCR) or does infection trigger a sustained self-loop immune reaction in CNS? |
| *Does intrathecal non-disease-related CSF IgG synthesis (i.e., the ‘MRZ’ pattern) really occur during HIV infection as in MS? |
| *Is non-specific IgG synthesis apparently supported by antigen-driven affinity maturation? |
| *Does the synthesis against non-relevant antigens (i.e., MRZ pattern), as commonly observed in MS, also occur in HIV-infected patients? |
| *Where are the CNS-resident IgG-secreting cells mainly situated (white matter parenchyma, basal ganglia, leptomeninges)? Are plasma cells isolated or associated with lymphoid structures? |
| *Are tertiary lymphoid organs (TLO) present in the CNS of HIV-infected patients? Does IgG affinity maturation occur in the CNS before cell migration through the BBB or is traffic two-way through it? |
| *Does chronic specific/non-specific intrathecal IgG synthesis play a role in the pathophysiology of some CNS lesions? Are there any slow-rate chronic CNS lesions around IgG-secreting cell infiltrates? |
| *Do CNS infiltrates of plasma cells (and therefore local IgG synthesis) correlate with basal ganglia or cortical atrophy/lesions as observed on MRI (Chiang et al., 2007)? |
| *Some of the typical markers of oxidative injuries (p22phox, oxidized phospholipids and iron) occurring in MS are also recovered in animal models of coronavirus infection, making chronic viral infection an interesting model of progressive MS lesions (Schuh et al., 2014). Besides the mimicking of some aspects of MS pathology, the coronavirus model is also characterized by a major intrathecal IgG synthesis, as in MS pathology and in HIV infection (Dorries et al., 1986, Schwender et al., 1991). Could these oxidative markers also be recovered in chronic CNS viral infection as in human HIV? |
| *Do the sub-pial lesions observed in MS and spatially correlated with meningeal TLO also exist in association with meningeal TLO in HIV infection? Such lesions are revealed only by anti-MBP or anti-PLP immunochemistry but not by classical staining (Bø et al., 2003). Sub-pial lesions have never been described but have only been researched in AIDS patients with PML in the vicinity of macroscopic PML lesions (Moll et al., 2008). Unfortunately, PML in AIDS probably precludes any cortical immune reaction owing to a profound immune suppression. Studies on well-controlled HIV patients would be more relevant. |
| *More generally, does the intrathecal immune reaction associated with HIV infection throw any light on chronic autoimmune intrathecal disorders like MS? |