Anti-ganglioside antibody induction by swine (A/NJ/1976/H1N1) and other influenza vaccines: insights into vaccine-associated Guillain-Barr? syndrome.

[Emily]

http://www.ncbi.nlm.nih.gov/pubmed/18522505
: J Infect Dis. 2008 Jul 15;198(2):226-33.Click here to read Links
Anti-ganglioside antibody induction by swine (A/NJ/1976/H1N1) and other influenza vaccines: insights into vaccine-associated Guillain-Barr? syndrome.
Nachamkin I, Shadomy SV, Moran AP, Cox N, Fitzgerald C, Ung H, Corcoran AT, Iskander JK, Schonberger LB, Chen RT.

Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283, USA. nachamki@mail.med.upenn.edu

BACKGROUND: Receipt of an A/NJ/1976/H1N1 "swine flu" vaccine in 1976, unlike receipt of influenza vaccines used in subsequent years, was strongly associated with the development of the neurologic disorder Guillain-Barr? syndrome (GBS). Anti-ganglioside antibodies (e.g., anti-GM(1)) are associated with the development of GBS, and we hypothesized that the swine flu vaccine contained contaminating moieties (such as Campylobacter jejuni antigens that mimic human gangliosides or other vaccine components) that elicited an anti-GM(1) antibody response in susceptible recipients. METHODS: Surviving samples of monovalent and bivalent 1976 vaccine, comprising those from 3 manufacturers and 11 lot numbers, along with several contemporary vaccines were tested for hemagglutinin (HA) activity, the presence of Campylobacter DNA, and the ability to induce anti-Campylobacter and anti-GM(1) antibodies after inoculation into C3H/HeN mice. RESULTS: We found that, although C. jejuni was not detected in 1976 swine flu vaccines, these vaccines induced anti-GM(1) antibodies in mice, as did vaccines from 1991-1992 and 2004-2005. Preliminary studies suggest that the influenza HA induces anti-GM(1) antibodies. CONCLUSIONS: Influenza vaccines contain structures that can induce anti-GM(1) antibodies after inoculation into mice. Further research into influenza vaccine components that elicit anti-ganglioside responses and the role played by these antibodies (if any) in vaccine-associated GBS is warranted.

[AlaskaDenise]

Re: Anti-ganglioside antibody induction by swine (A/NJ/1976/H1N1) and other influenza vaccines: insights into vaccine-associated Guillain-Barr? syndrome.

Axonal Guillain-Barr? syndrome: Relation to anti-ganglioside antibodies and Campylobacter jejuni infection in Japan

Kazue Ogawara, MD 1 *, Satoshi Kuwabara, MD 1, Masahiro Mori, MD 1, Takamichi Hattori, MD 1, Michiaki Koga, MD, PhD 2, Nobuhiro Yuki, MD, PhD 2
1Department of Neurology, Chiba University School of Medicine, Chiba, Japan
2Department of Neurology, Dokkyo University School of Medicine, Tochigi, Japan


*Correspondence to Kazue Ogawara, Department of Neurology, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan

Funded by:
Uehara Memorial Foundation (Japan)


Abstract

To clarify the relations of the axonal form of Guillain-Barr? syndrome (GBS) to anti-ganglioside antibodies and Campylobacter jejuni infection, 86 consecutive Japanese GBS patients were studied. Electrodiagnostic criteria showed acute inflammatory demyelinating polyneuropathy in 36% of the patients and acute motor axonal neuropathy (AMAN) in 38%. Frequent anti-ganglioside antibodies were of the IgG class and against GM1 (40%), GD1a (30%), GalNAc-GD1a (17%), and GD1b (21%). Identified infections were C. jejuni (23%), cytomegalovirus (10%), Mycoplasma pneumoniae (6%), and Epstein-Barr virus (3%). There was a strong association between AMAN and IgG antibodies against GM1, GD1a, GalNAc-GD1a, or GD1b. Almost all the patients with at least one of these antibodies had the AMAN pattern or rapid resolution of conduction slowing/block possibly because of early-reversible changes on the axolemma. C. jejuni infection was frequently associated with AMAN or anti-ganglioside antibodies, but more than half of the patients with AMAN or anti-ganglioside antibodies were C. jejuni-negative. These findings suggest that the three phenomena axonal dysfunctions (AMAN or early-reversible conduction failure), IgG antibodies against GM1, GD1a, GalNAc-GD1a, or GD1b, and C. jejuni infection are closely associated but that microorganisms other than C. jejuni frequently trigger an anti-ganglioside response and elicit axonal GBS. Ann Neurol 2000;48:624-631

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Received: 18 February 2000; Revised: 15 May 2000; Accepted: 16 May 2000

http://www3.interscience.wiley.com/journal/79502028/abstract?CRETRY=1&SRETRY=0

[AlaskaDenise]

Re: Anti-ganglioside antibody induction by swine (A/NJ/1976/H1N1) and other influenza vaccines: insights into vaccine-associated Guillain-Barr? syndrome.

The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barr? syndrome

Peggy C.R. Godschalk1, Astrid P. Heikema1, Michel Gilbert2, Tomoko Komagamine3, C. Wim Ang1, Jobine Glerum1, Denis Brochu2, Jianjun Li2, Nobuhiro Yuki3, Bart C. Jacobs4,5, Alex van Belkum1 and Hubert P. Endtz1

1Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
2Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada.
3Department of Neurology, Dokkyo University School of Medicine, Shimotsuga, Tochigi, Japan.
4Department of Neurology and
5Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Published December 1, 2004
Received for publication April 16, 2002, and accepted in revised form September 28, 2004.

Molecular mimicry of Campylobacter jejuni lipo-oligosaccharides (LOS) with gangliosides in nervous tissue is considered to induce cross-reactive antibodies that lead to Guillain-Barr? syndrome (GBS), an acute polyneuropathy. To determine whether specific bacterial genes are crucial for the biosynthesis of ganglioside-like structures and the induction of anti-ganglioside antibodies, we characterized the C. jejuni LOS biosynthesis gene locus in GBS-associated and control strains. We demonstrated that specific types of the LOS biosynthesis gene locus are associated with GBS and with the expression of ganglioside-mimicking structures. Campylobacter knockout mutants of 2 potential GBS marker genes, both involved in LOS sialylation, expressed truncated LOS structures without sialic acid, showed reduced reactivity with GBS patient serum, and failed to induce an anti-ganglioside antibody response in mice. We demonstrate, for the first time, to our knowledge, that specific bacterial genes are crucial for the induction of anti-ganglioside antibodies.

(the article is long, but good)

Last 2 paragraphs of discussion....

The associations that we found are not absolute. As host factors also play an important role in the pathogenesis of GBS, infection with a C. jejuni strain that expresses ganglioside-like structures is not sufficient to trigger GBS. In addition, a variety of ganglioside mimics, produced by different LOS classes, have been associated with GBS with diverse clinical manifestations (8, 20, 29). Furthermore, it is not clear at present whether all bacterial factors involved in the development of GBS/MFS have been identified.

After the demonstration of anti-ganglioside antibodies in GBS/MFS patient sera, and the subsequent identification of ganglioside mimics in Campylobacter LOS and of the specific host responses toward these epitopes, we now also demonstrate that the microbial gene repertoire is an important factor in the initiation of postinfectious autoimmune disease. The markers described in the current communication may facilitate the search for mechanisms of microbial pathogenicity and be helpful in the development of new molecular diagnostic tools for identifying C. jejuni strains with an increased ability to induce GBS/MFS. Furthermore, increased insight into the biosynthesis of ganglioside-mimicking structures may ultimately lead to the development of new treatment strategies and interventions (30).

http://www.jci.org/articles/view/15707/version/1

[gsgs]

Re: Anti-ganglioside antibody induction by swine (A/NJ/1976/H1N1) and other influenza vaccines: insights into vaccine-associated Guillain-Barr? syndrome.

http://www.ncbi.nlm.nih.gov/pubmed/19730016?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

There were 1000 cases (mean age, 47 years) of GBS reported after vaccination in the United States
between 1990 and 2005. The onset of GBS was within 6 weeks in 774 cases, >6 weeks in 101,
and unknown in 125. Death and disability after the event occurred in 32 (3.2&#37 and 167 (16.7%)
subjects, respectively. The highest number (n = 632) of GBS cases was observed in subjects
receiving influenza vaccine followed by hepatitis B vaccine (n = 94). Other vaccines or combinations
of vaccines were associated with 274 cases of GBS. The incidence of GBS after influenza vaccination
was marginally higher in subjects <65 years compared with those >or=65 years (P = 0.09); for
hepatitis vaccine, the incidence was significantly higher (P < 0.0001) in the <65 group.
Death was more frequent in subjects >or=65 years compared with those <65 years (P < 0.0001).
-------------------------
1990 to 2005 in the United Kingdom. The relative incidence of Guillain-Barr&#233; syndrome
within 90 days of vaccination was 0.76 (95% confidence interval: 0.41, 1.40).
In contrast, the relative incidence of Guillain-Barr&#233; syndrome within 90 days of an influenzalike illness
was 7.35 (95% confidence interval: 4.36, 12.38), with the greatest relative incidence (16.64, 95%
confidence interval: 9.37, 29.54) within 30 days. The relative incidence was similar (0.89, 95% confidence
interval: 0.42, 1.89) when the analysis was restricted to a subset of validated cases. The authors found
no evidence of an increased risk of Guillain-Barr&#233; syndrome after seasonal influenza vaccine. The finding
of a greatly increased risk after influenzalike illness is consistent with anecdotal reports of a preceding
respiratory illness in Guillain-Barr&#233; syndrome and has important implications for the risk/benefit
assessment that would be carried out should pandemic vaccines be deployed in the future.
http://www.ncbi.nlm.nih.gov/pubmed/19033158?ordinalpos=1&itool=EntrezSystem2.PEntrez. Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.P ubmed_Discovery_RA&linkpos=2&log$=relatedarticles& logdbfrom=pubmed
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[AlaskaDenise]

Re: Anti-ganglioside antibody induction by swine (A/NJ/1976/H1N1) and other influenza vaccines: insights into vaccine-associated Guillain-Barr? syndrome.

date for paper in gsgs post is:

1: J Clin Neuromuscul Dis. 2009 Sep;11(1):1-6

.

[Emily]

Re: Anti-ganglioside antibody induction by swine (A/NJ/1976/H1N1) and other influenza vaccines: insights into vaccine-associated Guillain-Barr? syndrome.

The 2009 study gsgs found seems more meaningful, (to me), than the studies that look at GBS risk from vaccines compared to background. This is the first time I've seen one compare it to the risk of GBS from the flu itself. (If I am understanding this correctly.) That is what you'd be interested in if a flu strain was circulating. I've wondered if the 1976 strain had circulated if it would have caused a lot of cases of GBS itself. If the HA is the trigger, that would make sense.

90 days of vaccination was 0.76 (95% confidence interval: 0.41, 1.40)
90 days of an influenzalike illness was 7.35 (95% confidence interval: 4.36, 12.38)

I'm never sure how to interpret these numbers. Is the indication here using 'relative incidence' that infection with the influenza virus could be several times more likely to trigger GBS than a flu vaccine?

[AlaskaDenise]

Re: Anti-ganglioside antibody induction by swine (A/NJ/1976/H1N1) and other influenza vaccines: insights into vaccine-associated Guillain-Barr? syndrome.

........
90 days of vaccination was 0.76 (95% confidence interval: 0.41, 1.40)
90 days of an influenzalike illness was 7.35 (95% confidence interval: 4.36, 12.38)

I'm never sure how to interpret these numbers. Is the indication here using 'relative incidence' that infection with the influenza virus could be several times more likely to trigger GBS than a flu vaccine?

That's the way I understand it.

To be fair, we should also compare to number of people gettting GBS from other diseases know to cause it - not just influenza.

.