Campylobacterjejuni/coli(CJC) infection has been implicated in the immunopathogenesis of Guillain-Barr6 syndrome (GBS), acute motor axonal neuropathy (AMAN), and Miller Fisher syndrome (MFS). However, its role in chronic immune mediated neuropathies such as multifocal motor neuropathy (MMN) or chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is less clear. Anti-ganglioside antibodies are associated with chronic motor neuropathies such as MMN and IgM anti-GM1, and IgM anti-asialo GM1 antibodies have been shown to cross-react with CJC lipopolysaccharides. Molecular mimicry between CJC and IgG anti-GM1 antibodies has also been suggested. Therefore we have performed a retrospective assessment of anti-cJC-specific IgG, IgM, and IgA antibodies in a cohort of seven patients with clinical and electrophysiologicaily definite MMN. The control group consisted of 140 healthy blood donors with no history of enteric illnesses. We found elevated titres of anti-CJC-speciflc IgG in 5 of 7 patients, IgM in 3 of 7 and IgA in 1 of 7. At least 1 anti-CJC antibody was elevated in 6 of 7 patients, and 3 patients had elevations of both IgG and IgM antibodies. Three patients had significantly elevated titres of anti-ganglioside antibodies without a clear relationship to the anti-CJC titres.
Therefore antibodies specific for CJC were found more frequently than expected in patients with MMN. Prior or ongoing infection with CJC may play a role in the aetiopathogenesis of MMN.
I do have the full paper if anybody wants the gory details.
The hypothesis that infection with CJC may trigger an immune response directed at myelin or axons is supported by the evidence of molecular mimicry and cross-reactivity between CJC and ganglioside epitopes in acute inflammatory neuropathies such as GBS, MFS and AMAN [emphasis added]. Cross-reactivity between anti-ganglioside antibodies from patients with chronic motor neuropathies and CJC epi- topes has also been demonstrated; however, the role of CJC in chronic neuropathies is not clear as this would require persistent antigenic stimulation to continue the immune process. This may be provided by molecular mimicry as has been shown between ganglioside epitopes and CJC lipopolysaccharides. Whether the excess cJc-specific antibodies in our cases also have anti-ganglioside actMty is unclear.
Although our results are suggestive of infection with CJC, and a possible role for CJC infection in the aetiopathogenesis of MMN, other possibilities need to be addressed. Passive transference of CJC antibodies was considered as all patients positive for CJC antibodies had previously, or are currently, receiving MG with Intragam (Commonwealth Serum Laboratories Australia) or Sandoglobulin (Sandoz), both of which are produced from pooled human serum. However, the use of these products would not explain the presence of IgA or IgM antibodies in 4 of the 6 seropositive individuals, as both products consist almost exclusively of IgG.22The possible transference of CJC-specific IgG is less clear as this was detected at a level of 1.30D units in Intragam. However, this figure is still less than that of two of the MMN cases and there would be considerable dilution after infusion. Furthermore, the patient with the highest level of CJC- specific IgG has not received IGT for 2 years (case 1), the reported half-life of IgG being 21 days2s and a patient who has had monthly IGT for 3 years (case 4) has a low level of CJC-specific IgG.
Persistence of class-specific anti-CJC antibodies is not readily explained as our own experience shows that IgM and IgA fall steadily over 4-6 weeks following CJC enteri- tis although IgG can persist for up to 6 months; longer follow-up information is not available. The persistence of antibody would suggest continued antigenic stimulation either from chronic infection, or persisting CJC cross- reacting antigens, possibly neural in origin. Whether cross-reaction with neural antigens such as gangliosides could produce a serological response mimicking CJC infection is unclear.
Although preliminary, these findings suggest a possi- ble role for infection with CJC in the aetiopathogenesis of MMN and warrant further investigation.