HLA-G Expression in Guillain-Barré Syndrome Is Associated with Primary Infection with Cytomegalovirus

GUILLAIN-BARRE SYNDROME (GBS) is an acute peripheral neuropathy characterized by a symmetric, usually ascending paralysis due to an acute inflammatory demyelination. GBS is considered the prototype of postinfectious illness with immunopathologic features that include an inadequate immune response against persistent foreign epitopes which cross-react with self-epitopes of peripheral nerves. Regarding this hypothesis, progressive understanding of the immunopathological phenomena leading to the persistence of infective agents in host may provide a rationale for targeting immunotherapy in GBS. In the field of immune tolerance, recent studies have focused on the role of the Human Leukocyte Antigen–G (HLA-G) molecules, which belong to the non-classical HLA class Ib molecules. HLA-G proteins differ from classical HLA-Ia molecules by their low polymorphism, their restricted tissue distribution in tumors (1), and pulmonary (5) or muscle inflammation (6). Furthermore, they exert immunotolerant functions in feto-maternal tolerance, heart-graft acceptance, and tumor immunoevasion (1). Lastly, in a previous report, we evidenced HLA-G expression on monocyte-macrophages during human cytomegalovirus (HCMV) reactivation. We proposed this phenomenon as a new mechanism that could help HCMV eluding host defences and persisting in human body (4). Consequently, and because CMV infection is the most common viral disease causing GBS (2), we examined HLA-G expression on peripheral monocytes in a patient with a GBS induced by HCMV primary infection. A 41-year-old man presented with a bilateral ascending paresthesias and a progressive weakness in lower limbs. On admission, he was afebrile, presented with areflexia of the lower limbs, and had progressively developed a flaccid ascending tetraparesis. GBS was confirmed by elevated CSF protein concentration (0.6g/L) without cellular response and an absence of spinal cord compression on CT scan. Electrophysiological studies showed slow motor conduction, increased distal latencies, an abolition of F waves, and a normal sensory parameters. Acute HCMV infection was proved by high anti-CMV IgM and IgG antibodies, and positive blood PCR (3). Primary infection was demonstrated by an urea denaturation test showing predominance of low-avidity IgG produced early in infection. Tests for other viruses (HSV, HIV, HAV, HBV, and HCV) remained negative. Despite treatment by immunoglobulins and ganciclovir, the patient developed respiratory failure and required mechanical ventilation for 2 months. Recovery was slow, and he was discharged 3 months after admission. We evidenced HLA-G expression on some of the patient’s blood monocytes by allogeneic stimulation. Briefly, monocytes were isolated at the onset of the disease by Ficoll density gradient centrifugation and