Antibodies against GM1, IL6 and IL6R in the serum of patients with polyneuropathies
HATZIFILIPPOU E., KOUTSOURAKI E., COSTA V., BALOYANNIS S.J.

Polyneuropathies are demyelinating lesions involving several immunological processes in the development of unpredictable exacerbation and remissions leading to chronic progressive course.

The proinflammatory cytokines such as Intelreukin 6 (IL-6) and its soluble receptor (IL-6R) play an important role in the initiation and maintenance of the inflammatory reaction in demyelinating diseases.

The macrophages are known sources of IL-6 and are candidate cells to express IL-6 in human polyneuropathies. They attack intact myelin sheaths wrapped around healthy axons. The endoneurial macrophages are likely to act as local antigen-presenting cells by their capability to express major histocompatibility complex antigens and costimulatory B7-molecules and they may be critical in triggering the autoimmune processes. Then the hematogenous macrophages could find their way into the peripheral nerve in association with T-cells by the concerted action of adhesion molecules (CAMs), matrix metolloproteases (MMPs) and chemotactic signals. Within the nerve, macrophages regulate the inflammation by secreting pro-inflammatory cytokines such as IL-6 and TNFa. They are guided towards their targets presumably by autoantibodies and attack them in a complement-dependent receptor-mediated way.

Another important factor which seems to have a crucial role in demyelinating diseases are the anti-ganglioside antibodies.

Gangliosides are acidic glycophospholipids localized in the outer layer of plasma membranes. They contain sialic acid, one (by GM1) or two (by GD1), which is usually N-acetyl-neuraminic acid as well as N-glycolyl-neuraminic acid, linked to an oligoglycosyl backbone attached to a ceramide base. The hydrophobic ceramide is immersed in the lipid membrane and 52 when the hydrophilic carbohydrate structure is exposed extracellulary, as it happens in the plasma membranes, they are capable in acting as an autoantibody target.

The aim of the present investigation was to determine and compare the concentration of Anti-GM1, IL-6 and IL-6R in the serum of patients with polyneuropathies.

We have examined 20 patients (12 females, 8 males) aged from 17-78 years old; all patients suffered mainly from kinetic type of polyneuropathies, whereas some others suffered from sensory or sensory-motor polyneuropathy based on clinical and neurophysiological investigation. In addition, the majority of these patients received IgG (IV) and all of them demonstrated clinical improvement. Serum GM1, IL-6 and IL-6R were determined by the use of commercial available ELISA kits.

According to our results 90% of the patients demonstrated elevated anti-GM1 IgM concentration, (mean 34,74 EU/ml) in dilution 1:200, which indicates that patients with polyneuropathies, especially with a kinetic type of the disease, elicit high levels of antibodies against GM1, which cause the demyelination of peripheral nerves.

Although the patients in our study received intravenous immunglobulin, high levels of anti-GM1 IgM were detected in their sera. This indication means that the treatment shall be longer than six months, in order to detect decreased levels of anti-GM1 antibodies.

According to our results, 75% of the patients with high anti-GM1 concentration demonstrated elevated IL-6 values (20,12 pg/ml). 45% of the patients, who demonstrated elevated concentrations of IL-6, showed dicreased sIL-6R (mean 40 ng/ml), whereas the proportion of decreased sIL-6R did not differ from that of patients with normal sIL6R. However, our results concerning the relationship between sIL-6R and IL-6 are in accordance with previous studies.

Based on our study, there was an association between the presence of increased anti-GM1 IgM levels in the serum and the elevated IL-6 values. However, we didn't found any significant correlation between type of treatment and IL-6 levels.

Further investigation is required in order to establish the exact action of antibodies against GM1, IL-6 and sIL-6R in polyneuropathies and to figure out the existant correlation between IgG-treatment and the levels of those cytokines in the serum of the patients.

Key words: Anti-GM1 in polyneuropathies, IL6, IL-6 receptor, peripheral neuropathies, neurochemistry.