Increased Immune Reactivity to Central Nervous System Derived Naturally Presented Peptides in Patients with Active Multiple Sclerosis

Because the immune response to positive control mitogen PHA and antigen tetanus toxoid and the peptide derived from tetanus toxoid did not differ between patients with active or inactive disease and controls, we take it as improbable that there is a general immune hyperreactivity in patients with active MS. However, we did observe higher IFN-γ-secreting cells in patients with active MS in response to the tested peptides derived from JC virus and Chlamydia pneumoniae. Because many adults are carriers of anti-JC virus antibodies without signs of infection, it is imaginable that immune responses to this virus increase during inflammatory processes affecting the CNS.9 Concerning a possible role of Chlamydia pneumoniae in MS, data are contradictory.10 In conclusion, our data represent the first functional analysis of T-cell reactivities to peptides of the ligandome of MHC molecules expressed in the CNS of patients with MS. Our results indicate that although IFN-γ responses to naturally presented peptides are detectable in healthy controls as well as in patients with MS, the number of antigen-specific IFN-γ-secreting cells is significantly enhanced in patients with active MS. Future studies are necessary to determine whether the tested naturally presented peptides might play a role in the pathogenesis of MS, either as primary targets of the autoimmune response or as antigens presented at a later stage of the disease because of antigen spreading.\n5 y Positive Positive Fingolimod (Gilenya) None known MS50 46 M RRMS Inactive 15 y Positive Positive IFN-β-1a (Avonex) Congenital hydrocephalus MS51 59 F RRMS Inactive 36 y Positive Not known None None known Controls HC1 49 F HC   Negative   None known HC2 23 F HC   Negative   None known HC3 18 F HC   Negative   None known HC4 23 M HC   Negative   None known HC5 34 F HC   Negative   None known HC6 31 F HC   Negative   None known HC7 28 M HC   Negative   None known HC8 49 F HC   Positive   None known HC9 35 F HC   Negative   None known HC10 25 F HC   Negative   None known HC11 32 M HC   Negative   None known HC12 48 F HC   Positive   None known HC13 28 M HC   Positive   None known OND1 34 F OND (cavernoma) Negative Negative None None known OND2 57 F OND (paraneoplastic stiff man syndrome) Positive Not known None Hypothyroidism, arterial hypertension, pernicious anemia OND3 53 M OND (limbic encephalitis) Negative Negative Intravenous immunoglobulins until 2 wk before