GBS and GM1b Antibody
Abstract & Commentary
Source: Ogawara K, et al. Anti-GM1b antibody is associated with acute motor axonal neuropathy and Campylobacter jejuni infection. J Neurol Sci. 2003;210:41-45.
Anti-ganglioside peripheral nerve antibodies in Guillain-Barré syndrome (GBS) include GM1, asialo-GM1, GQ1b, GD1a, and GT1a. GM1 is associated with pure motor GBS and with the acute motor axonal variant of GBS. GM1b is also associated with GBS, but often its role in the disease is obscured by the concomitant presence of GM1. The role of GM1b in the absence of GM1 remains to be defined.
Among 86 consecutive GBS patients (mean age, 38 years), 24 had both GM1 and GM1b antibodies, whereas 10 each had either GM1 or GM1b antibodies but not both. Of the 10 GM1b-positive/GM1-negative patients, 4 each also demonstrated either GD1a or GalNAc-GD1 antibodies, and 1 showed multiple other antibodies including GD1a, GD1b, GQ1b, and GT1b. None had GM2 antibody activity. Of the 10 GM1b-positive/GM1-negative patients, 60% had Campylobacter jejuni infection, 50% had a diarrheal prodrome, and 80% had a diagnosis of acute motor axonal neuropathy (AMAN) with no sensory loss. One patient was unclassifiable electrodiagnostically, and 1 demonstrated changes typical for acute inflammatory demyelinating polyneuropathy on nerve conduction studies. Peak clinical disability and incidence of slow recovery did not differ among those who were GM1b-positive/GM1-negative and those GM1b-negative/GM1-positive. Like GM1, GM1b may be a target neural antigen in AMAN following C jejuni infection.
Separation of GM1 antibody into immunoglobulin (IgG) subclasses (IgG1 to 4) suggests that a correlation exists between the particular IgG subclass on one hand and the clinical profile and recovery pattern on the other.1 Among 42 patients with GM1-antibody-positive GBS, the most frequent subclasses present were IgG1 (n = 32, 76%) and IgG3 (n = 13, 31%). Four patients demonstrated positivity for both IgG1 and IgG3. IgG4 was not seen in any patient; IgG2 was positive in 2 (5%). C jejuni serologic positivity and preceding gastrointestinal symptomatology (56% and 63%, respectively) were more common with the former, while antecedent respiratory infection was associated with the latter (77%). No correlation was found between IgG subclass and age, sex, GM1 antibody titer, or median nerve motor potential amplitude. Excluding patients with both IgG1 and IgG3, inability to walk independently at 1, 3, and 6 months following disease onset was more likely in IgG1-positive patients, although nadir disease severity was similar in both IgG1 and IgG3 groups. IgG3 patients were more likely to appreciate rapid recovery, defined as improving by 2 or more Hughes grades from nadir, within the first month of illness. Among GM1-antibody-positive patients, those with the IgG3 subclass of GM1 were more likely to fare better.
How does GM1 antibody mediate its pathogenicity? Sera from 24 GBS patients was obtained to study its ability to influence leukocyte functions including degranulation and phagocytosis.2 Anti-GM1 antibody-negative serum served as controls. Sixty-seven percent (10 of 15) and 53% (8 of 15) of GM1 antibody-positive sera were able to induce white cell degranulation and phagocytosis, respectively, whereas none of the control sera had such effect. Activation of leukocyte inflammatory functions may be the mechanism of GM1 antibody activity in GBS patients. — Michael Rubin
Dr. Rubin is Professor of Clinical Neurology, New York Presbyterian Hospital - Cornell Campus.
1. Koga M, et al. Neurology. 2003;60:1514-1518.
2. van Sorge NM, et al. Ann Neurol. 2003;53:570-579.