Guillain-Barré syndrome is often a post-infectious, immune-mediated nerve injury, believed to be associated with Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, influenza A, Mycoplasma pneumoniae, Haemophilus influenzae, hepatitis (A, B, and E), and more recently, Zika virus infections.
The Guillain-Barré syndrome (GBS) is considered a T helper 1(Th1) cells-mediated acute inflammatory peripheral neuropathy.
Th1 cells, a subset of CD4+T (T helper) cells, are dominant in the inflamed nerves at the acute phase of GBS, which could produce IFN-γ as a major pathogenic cytokine in GBS, because increased IFN-γ was seen in the serum of GBS patients at acute phase, and higher immunoreactivity for IFN-γ was showed in sural nerves biopsies of GBS patients. However, some changes in GBS and EAN could not be explained by Th1 cell pathogenic role. Most likely, it is complex and involves multiple factors in GBS.
T helper 17 (Th17) cells have been identified as an obvious distinct Th population and a novel Th lineagemediating tissue inflammation and autoimmune response in both animal models and humans. Th17 cells can induce local inflammation in the target organs and help B cells to produce antibodies, two of the hallmarks of GBS pathology. Th17 cells mainly produce IL-17A, which could be promoted by IL-23 in vitro and in vivo. In addition to IL-17A, Th17 cells can secrete IL-17F, IL-21, and IL-22, which induces massive tissue reactions by promoting the recruitment of inflammatory cells, while IL-22 shows specific biological characters, such as tissue repairing and wound healing
However, the role of Th17 and Th22 cells as well as their cytokines in the pathogenesis of GBS is still unclear.
In the Li et al, report published in the journal Mediators of Inflammation, the authors measured the frequency of Th1, Th17, and Th22 cells in the peripheral blood and levels of IL-17 and IL-22 in plasma of GBS patients at the acute and the plateau phases to unravel the mechanisms by which Th17 and Th22 as well as their cytokines may play a pathogenic role in GBS.
This report indicates that in the early, acute phase of Guillain-Barré syndrome circulating Th17, Th22 cells and Th1 cells are increased along with the plasma levels of IL-17 and IL-22 at the acute phase.
Thus, it is speculated that Th17 and Th22 cells as well as IL-17/IL-22 are involved in the initiation and development of GBS and IVIg treatments effectively reduce their levels and attenuateclinical signs of GBS.
Of note, intravenous immunoglobulin therapy (IVIg) treatment was able to down-regulate these cells and their cytokines at the plateau phase of GBS, and to attenuate clinical signs of GBS.
In summary, elevated circulating Th17 and Th22 cells may contribute to the pathogenesis of GBS. IVIg mediates its therapeutic effects by downregulating these cells and their cytokines in GBS. Our data suggest that antagonists of Th17 and Th22 cells and their cytokines may have therapeutic potentials for alleviating GBS in humans.