HLA-B27 and Ebringer BSE text

This is a huge post, probably of very little interest to anyone, about the BSE/acinetobacter hypothesis. I'd just re iterate that, as pointed out by Johnn on the first Ebringer post comments, no one can say if the BSE was caused by the antibodies to acinetobacter or whether the antibodies were formed to the prion-damaged brain tissue and they happen to cross react with bacterial antigens as a coincidence. It's a long slog to read, go there if you wish but it's not really nutrition. It does gives a window in to how funding works. The work here was done for "small change" in terms of funding.

Peter

OK, here's the text:





BOVINE SPONGIFORM ENCEPHALOPATHY


This is a report on Government commissioned

research into the autoimmune theory of “bovine

spongiform encephalopathy” or BSE.


In 1997 (CSA 4302) and in 1999 (CSA 5115) the Government

through the Ministry of Agriculture, Fisheries and Food

(MAFF) (Now, Department of the Environment, Food and

Rural Affairs) (DEFRA) authorized and funded 2 studies into

the possibility that BSE could be an autoimmune disease.


The following report is the result of these studies which

were carried out at King’s College (University of London) in

the Department of Life Sciences, under the supervision of

Prof. Alan EBRINGER B.Sc,MD,FRCP,FRACP,FRCPath.






(1) Costs of commissioned studies:

(1a) CSA 4302: £ 18,032

The first study commissioned in 1997 involved a pilot study to determine, whether BSE animals had antibodies to a soil bacterium,
Acinetobacter calcoaceticus, after it had been shown that this microbe possesses molecular sequences resembling bovine and human brain tissues (Ebringer et al., Environmental Health Perspectives 1997; 105: 1172-1174) (Paper 1 in Appendix)

The results of the pilot study were published in “Infection & Immunity”, a journal of the American Society of Microbiology.
(Tiwana et al., Infection & Immunity 1999; 67: 6591-6595).
(Paper 2 in Appendix)


(1b) CSA 5115: £ 216,228

The second study commissioned in 1999 involved an investigation of
128 BSE animals and 127 healthy controls, after the pilot study involving 29 BSE affected animals compared to 102 healthy ones showed elevated titres of antibodies to Acinetobacter but not to 2 other
control bacteria.


The combined results of these two studies, involving 157 BSE affected animals and 229 healthy ones, form the basis of this report.



Total costs of commissioned studies: £ 234,260.





(2) Background to BSE problem:

BSE is a neurological disease of cattle, that appeared in the U.K.,
following changes in the preparation of “meat-and-bone meal” (MBM) or “winter feed”, based on abattoir materials obtained from brain, spinal cord, pancreas and guts with their contents.

By 1988, some 60,000 cows had been identified as suffering from BSE and scientists from the “Ministry of Agriculture, Fisheries and Food” (MAFF)(Now DEFRA), suggested that “brains” in the “winter feed” could have been contaminated by “prions” or similar agents, from sheep having had scrapie and thereby probably caused BSE in cattle.

The use of these “winter feed” or MBM preparations was banned and since then the incidence of BSE in British herds has drastically fallen, although not to zero levels. (See figure, adapted from P. Brown
in Brit Med J, 2001;Vol.322;841-843)








(3) Theories of BSE:

Several theories have been proposed as the cause of BSE.

It has been suggested that BSE could be caused by viruses (1), organo-phosphates (2) or by “proteinaceous infectious particles” or “prions” (3).

“Normal prions” are cell membrane proteins, which are found in almost all organs, but in highest concentrations in brain tissues and are encoded by a gene found on chromosome 20 in humans.

Professor PRUSINER from San Francisco has suggested that “abnormal prions” convert “normal prions” into infectious particles which then probably cause various neurological diseases, such as scrapie in sheep, “kuru” in New Guinea natives from the Fore tribe,
BSE in cattle and Creutzfeldt-Jakob disease (CJD) in man.

How these diseases are transmitted is unknown, but it has been suggested that consumption of meat or brain tissues, containing such “abnormal prions” could start the conversion of “normal prions” into
infectious particles and thereby produce these neurological diseases, either in animals or man.

Although the “prion theory” has wide acceptance it also has some serious limitations:

(3.1) “Prions” as independent, infectious particles have not been demonstrated to be present in the environment.

(3.2) The absence of nucleic acids in the “abnormal prions” raises the
molecular biology issue of how diversity can occur without DNA, given that many “different strains” have been described.







(4) Spongiform changes in brain and BSE

The microscopical examination of brain tissues, from animals who had died from scrapie or BSE, showed characteristic “spongiform changes” and these diseases were therefore described as “spongiform
encephalopathies”.

Similar changes were observed in patients who had died from CJD.

Injection of brain tissues from sheep affected by scrapie or cows suffering from BSE, into experimental animals led to the development
of a neurological disease characterized by tremors, ataxia or progressive loss of control of limb movements and eventually death.

These features of tremors, progressive loss of control of limb movements, especially hindquarters, are also characteristic of animals affected by BSE.

Microscopical examination of the brains of these experimental animals, showed “spongiform changes” and similar observations were made in the human diseases sporadic CJD and kuru.

Since the neurological and microscopical features of the condition had been transmitted to experimental animals, these diseases were grouped together under the name of “transmissible spongiform encephalopathies” or TSE’s.

Could TSE’s be autoimmune diseases?

What are autoimmune diseases?










(5) Autoimmune diseases and rheumatic fever

“Autoimmune diseases” are characterised by presence of antibodies, which bind to “self-tissues” and are therefore known as “autoantibodies”. In some diseases such autoantibodies can cause tissue damage. Many human diseases, such as multiple sclerosis, juvenile diabetes and rheumatoid arthritis are considered as examples of autoimmune diseases.
The origin of such autoantibodies is unknown, but two main theories have been proposed: either the immune system spontaneously
starts producing tissue damaging immune cells or infection occurs by a microbiological agent, which possesses structures, showing molecular similarity or “molecular mimicry” with some of the tissues of the host.
Following infection, antibodies will be produced against the invading microbe and a portion of these antibodies will bind to self tissues of the host, acting as autoantibodies. When present in high concentrations, such autoantibodies can cause tissue damage and eventually lead to a disease involving the organ possessing structures resembling the invading pathogen.
A classical example of such a disease is “rheumatic fever”.
The microbe Streptococcus possesses molecular sequences which resemble the human heart. Following a severe upper respiratory tract
infection or tonsillitis, anti-streptococcal antibodies bind to human heart tissues and cause tissue damage. The patient develops a cardiac murmur, fever and muscle pains and is then said to suffer from “rheumatic fever”.
Since autoantibodies cause tissue damage, this is an example of an autoimmune disease produced by an infection.
Rheumatic fever has more or less disappeared in the Western World, over the last forty years.
It has been suggested that the widespread use of penicillin and similar antibiotics to control early streptococcal infections, since 1960’s, has led to the virtual disappearance of rheumatic fever, although in the Third World, it is still a relatively common disease.
The question arises whether other autoimmune diseases could be
prevented by the early removal of the offending microbe.



(6) Autoimmune diseases at King’s College London

Over the last thirty years, scientific work at King’s College London, has been involved in trying to find microbes, like Streptococcus in rheumatic fever, which would explain other autoimmune diseases.

The microbe Klebsiella has been found to be involved in the disease “ankylosing spondylitis” (AS) which manifests itself as recurrent backache, especially in young people and affects some half million individuals in the U.K. (4).

The microbe Proteus, which causes upper urinary tract infections, especially in women, has been found to be involved in the disease “rheumatoid arthritis” (RA) which manifests itself as severe arthritis, predominantly of the small joints of hands and feet, and affects some one million individuals in the U.K. (5).

In both AS and RA, autoantibodies are found against the white cell
blood groups (Human Leucocyte Antigens - HLA) linked to these diseases (HLA-B27 in AS and HLA-DR4/1 in RA) (6) and also against various types of collagens (7).

During active phases of the disease, elevated levels of antibodies
against Klebsiella are found in AS and against Proteus in RA (8).

When patients are in inactive phases of the disease, the levels of anti-bacterial antibodies fall to normal levels.

Drugs which interfere with cell divisions and reduce antibody production such as methotrexate, have been shown to produce therapeutic improvements in controlled trials in both diseases.

Dietary control aimed at reducing Klebsiella in AS (9) and
Proteus in RA (10) have led to some therapeutic benefits.






(7) Autoimmune diseases and BSE

Since BSE was thought to have arisen in cattle by feeding them modified MBM preparations, containing a pathogenic neurological agent, the late Emeritus Professor of Microbiology at King’s College London, John PIRT, raised the possibility, that as we were treating the autoimmune diseases AS and RA by diet, BSE could also be an autoimmune disease.

Dr. Clyde WILSON, from our group, who had been working on AS and RA, pointed out that in 1980, the GAJDUSEK group from Washington demonstrated the presence of autoantibodies to brain tissues in patients with kuru and CJD (11) and in sheep affected by scrapie (12).

Furthermore mice with a deficient immune system (SCID – Severe Combined Immuno-Deficiency) would not develop a neurological disease when injected peripherally with brain tissues from animals affected by scrapie (13).

This was most unusual, since SCID animals readily die from viral and bacterial infections, yet in this case the opposite from the expected outcome was happening - the agent was unable to produce the disease.

The orthodox explanation was that “prions” require a normal immune system to proliferate, but to an immunologist, an alternative explanation immediately suggests itself:


NO IMMUNE SYSTEM = NO DISEASE,


THEREFORE THE IMMUNE SYSTEM IS CAUSING THE
DISEASE

THEREFORE “BSE” COULD BE AN AUTOIMMUNE DISEASE.


THE QUESTION AROSE: WHICH MICROBE TRIGGERS BSE ?



(8) Experimental allergic encephalomyelitis and BSE

“Experimental allergic encephalomyelitis” (EAE) is an animal model of an autoimmune disease and is thought to resemble “multiple sclerosis”.

It was discovered by accident, over 120 years ago, in 1880 by the French immunologist, PASTEUR, when he first described anti-rabies immunisation.

PASTEUR and colleagues immunised humans who had been bitten
by rabid dogs or wolves, with brain homogenates from rabbits which had been infected with rabies.
Some patients developed anti-rabies immunity but a proportion, some one hundred individuals died of a disease which was labelled as
“allergic encephalomyelitis”.

The cause for this unexpected and lethal response was not explained till the 1930’s, when it was shown that injection of foreign brain homogenates will evoke an immune response in the immunised individual or animal by the production of anti-brain autoantibodies which will damage the brain tissues of the host (14).

In the 1950’s it became apparent that this was a general observation in immunology: immunisation with any organ homogenate would produce an autoimmune disease in the target organ.
The classical work of ROSE and WITEBSKY from Buffalo, demonstrated that peripheral injection of homogenates of thyroid tissue produced an experimental disease in animals which was similar to the human autoimmune disease “Hashimoto’s thyroiditis”.

Injection of brain homogenates from animals with BSE or scrapie led to a neurological disease and this was described as transmission of the disease: However the question arose whether this was not an example of “allergic encephalomyelitis”, the disease PASTEUR had observed one hundred years earlier.



(9) Spongiform changes in EAE, bovine myelin and Acinetobacter

In “acute EAE”, observed one to three weeks, following immunisation with brain homogenates, there is perivascular infiltration with inflammatory cells in brain vessels.

However in “chronic EAE”, observed three to six months, following immunisation, characteristic “spongiform changes” have been described, at least in rabbits in 1969 (15) and in guinea pigs in 1974 (16), by RAINE’s group from New York.
It would appear that “spongiform changes” also occur in EAE.

The factor in the central nervous system responsible for EAE is a basic protein present in myelin, the white matter of the brain.

In 1970, EYLAR’s group from San Diego, identified a highly active peptide from bovine myelin, which when injected in microgram quantities into guinea pigs, would produce hind leg paralysis, tremors, weight loss and death (17).

These features of hind quarters paralysis, tremors, weight loss and death, are also the features described in cattle affected by BSE.

Furthermore, the biological activity of this peptide was retained when it was heated to 100ºC for one hour or treated with 8 molar urea and these are properties also described for “prions”.

We proposed the hypothesis that there may be in the environment a microbe which could possess a protein resembling “brain tissues”, similar to the situation of Streptococcus in rheumatic fever.

Computer analysis of proteins in bacteria, using the EYLAR sequence from bovine myelin as a probe, revealed that the microbe Acinetobacter, which is present in soil, contaminated water and fecal materials had such a sequence. (Ebringer et al., Env. Health Perspect. 1997,105: 1172-1174) (Paper 1 in Appendix)




(10) Acinetobacter, molecular mimicry and BSE

The discovery that the common environmental microbe Acinetobacter, which is found in muddy soils and on the skin of animals and man, has a sequence resembling brain tissues, suggested a possible mechanism, as to how cattle could have developed BSE.

Offal material from abattoirs was used in the preparation of MBM
and could have inadvertently become contaminated by Acinetobacter.

Although heat treatment was still applied, the demonstration by EYLAR and co-workers, that these peptides were highly resistant to heat denaturation meant that if these bacterial fragments were present in MBM, then not only would the cows make antibodies against them but because of “molecular mimicry” or similarity between brain tissues and Acinetobacter (See figure), any antibodies produced would also attack the brain and cause a neurological disease.

The mechanism proposed is similar to the situation of Streptococcus in rheumatic fever and if such antibodies could be demonstrated in affected animals then this would make BSE an autoimmune disease.

Molecular mimicry between EYLAR peptide and Acinetobacter (Adapted from Env.Health Perspect. 1997;105: 1173 - Fig.1)





(11) BSE as an autoimmune disease

If BSE were to be an autoimmune disease, then two important immunological features would appear to be necessary:

(11.1) IgA antibodies

The mucosal immune system produces a characteristic antibody, the IgA isotype.
Over 90% of mucosal immunity is accounted for by the gastro-intestinal tract.
If Acinetobacter peptides had been present in the MBM feeds, then the highest relative levels of antibodies should be present in the IgA class.


(11.2) Autoantibodies

Since the EYLAR probe consisted of myelin peptides, following exposure to Acinetobacter peptides, autoantibodies should be present against myelin, the white matter of the brain.

However GAJDUSEK’s studies had shown that autoantibodies in kuru, CJD and in animals with scrapie were present against neurofilaments, which are components of the gray matter of the brain.

Thus autoantibodies should be present against both white and gray
matter components of the brain.


MAFF was approached with our idea that BSE could be an autoimmune disease caused by Acinetobacter infection.

The Chief Scientist at MAFF, Dr. David SHANNON, agreed that a pilot study should be carried out and provided resources and access to BSE and control sera.




(12) Results of pilot study (CSA 4302) : Acinetobacter antibodies

(12.1) Sera from animals with and without BSE
MAFF provided sera from 29 animals which had been found at post-mortem to satisfy the criteria of BSE and 18 animals which did not have the disorder. The sera were supplied by the Central Veterinary Laboratory (CVL) at New Haw, Addlestone, Surrey.
The 18 animals which did not have BSE had been referred to CVL because of abnormal behaviour involving ataxia and suggesting a neurological disease. Post-mortem examinations were carried out to exclude BSE.
The majority of BSE positive animals came from dairy Friesian
herds.

(12.2) Sera from animals from an organic farm
In addition, sera were obtained from an additional 58 healthy animals to act as extra controls: 30 serum samples from animals aged less than 30 months (8 Friesians and 21 Hereford-Friesian and one Charolais-Friesian crossbreeds, the crossbreeds being raised for meat production) and 28 serum samples from animals aged more than 30 months, all of which were dairy Friesians.
The animals were raised on a farm where no cases of BSE had been
reported and were kept under organic farming conditions, with winter feeds consisting of hay and grains but no MBM supplements.
Serum samples were obtained during annual herd testing for brucellosis.

(12.3) Antibodies to Acinetobacter

Antibodies to Acinetobacter calcoaceticus were significantly elevated in the 29 BSE animals, when compared to the 18 CVL controls (p<0.001), 30 organically raised cows aged less than 30 months (p<0.001) and to 28 organically raised cows aged more than 30 months (p<0.001), but no such elevations were found against 2 control bacteria E.coli and Agrobacterium. (See Fig.2a in Tiwana et al., Inf & Immunity 1999;67: 6591-6595) ( Paper 2 in Appendix)




(13) Results of pilot study (CSA 4302): Autoantibodies.

High levels of autoantibodies were found against both, bovine neurofilaments (Fig.1a) which are components of gray matter of the brain and also against bovine myelin (Fig.1b) which are components of the white matter of the brain.

These autoantibodies could be absorbed out with Acinetobacter
bacteria.

The highest levels were found in the IgA isotype suggesting that these antibodies had been produced following exposure to Acinetobacter antigens across the gut mucosa and not as a result of brain damage produced by “prions”.

This is the first report of autoantibodies to brain components in BSE.




(14) Results of study (CSA 5115): Specific antibodies to Acinetobacter.

In view of the results of the pilot study, a grant was submitted to MAFF, to study whether injection of Acinetobacter bacteria into experimental animals would reproduce a “spongiform disease”, resembling BSE.

This grant was rejected but another one approved to determine, firstly whether a larger series of samples from BSE affected animals would confirm the original results of the pilot study and secondly to ascertain whether such antibodies could be used to obtain an ante-mortem test for BSE, so that cases of affected animals could be excluded from entry into slaughter houses and therefore the human food chain.

The results so far obtained confirm the data from the pilot study.

Antibody responses were measured to Acinetobacter, Pseudomonas,
Bacillus, E. coli, Serratia, Proteus and Klebsiella, in 128 BSE positive animals, 63 BSE negative animals and 64 healthy control animals.

Elevated levels of antibodies to Acinetobacter (p<0.0001) and against Pseudomonas (p<0.001) were found in the BSE affected animals when compared to BSE negative animals or to healthy controls.

There was a significant elevation against Pseudomonas in BSE affected animals, although not as high as against Acinetobacter .
These two microbes are related in that both have molecular sequences resembling the EYLAR peptide. (See paragraph 9)

In the pilot study no elevation in antibodies was found against Agrobacterium and therefore the results of these two combined studies indicate that specific elevation of antibodies to Acinetobacter is present in BSE affected animals but not against six other bacteria.




(15) Results of study (CSA 5115): IgA gut antibody responses

The simplest explanation for the presence of specific antibodies to Acinetobacter bacteria in BSE affected animals is that they have been exposed either to the whole bacteria or bacterial fragments which then produced specific brain autoantibodies and these may have been responsible for the disease.
There are two main competing theories in trying to explain the origin of BSE, the “prion” theory and the autoimmune theory.

These two theories have been compared over ten different biological and medical criteria, and in each case they predict different
experimental observations and veterinary or clinical outcomes which are relevant to policy decisions in the field of health, food safety and the cattle industry. (See Table overleaf) (Ebringer et al., J. of Nutrit. & Env. Medicine, 1998; 8: 265-276)(Paper 3 in Appendix)

If the autoantibodies are produced by exposure to Acinetobacter fragments in the MBM feeds, then the highest relative levels should be present in the mucosal IgA antibody class (Points 2 and 5 of comparison of theories) (See Table overleaf)

The levels of IgA, IgG and IgM autoantibodies to bovine neurofilaments and bovine myelin have been measured in 128 BSE affected animals and compared to 127 healthy ones (Controls = 100%)

The relative increases in the immunoglobulin classes in the BSE animals, for neurofilaments was as follows: IgA (191%), IgG (173%) and IgM (143%) and for bovine myelin it was: IgA (184%), IgG (147%) and IgM (109%).

These results have been submitted for publication.

If brain damage had been caused by “prions” and evoked the formation of autoantibodies, it is difficult to see why they should have predominantly stimulated gut immunity, but presence of Acinetobacter in MBM feeds readily explains IgA responses.






(16) Results of study (CSA 5115): Peptide studies and M.A.N. assay

Antibody levels have also been measured against synthetic peptides,
consisting of 16 amino acids in length and representing EYLAR peptide (bovine myelin), Acinetobacter peptide (in enzyme 4-carboxy-mucono-lactone decarboxylase) and neurofilament peptide.

These measurements were combined into an algorithm the Myelin-
Acinetobacter-Neurofilament (M.A.N.) assay and values calculated for
28 BSE affected animals compared to 18 healthy ones.

The results show that all 28 BSE animals could be separated from the healthy ones - in that the BSE animals exceeded the 99.9% confidence limit (p<0.001) of the 18 controls. (See figure)

These results were presented at the Cambridge Healthtech Institute 2nd Annual International Meeting on “Transmissible Spongiform Encephalopathies”, which was held in Alexandria, Virginia, U.S.A. in October 2000. (Paper 4 in Appendix)



Further peptide studies with larger numbers of BSE and control sera are in progress.




(17) Antibodies to Acinetobacter in multiple sclerosis

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the nervous system affecting some 80,000 individuals in the U.K.

Although there are many different clinical manifestations of MS, a lower limb ataxia, characterised by difficulty in walking, is a well recognised feature of the disease.

Since hind quarters paralysis is a characteristic feature of both EAE and BSE, and since EAE is considered an animal model of MS, the question arose whether antibodies to Acinetobacter, a ubiquitous environmental microbe possessing sequences resembling brain tissues, could also be detected in this disease.

Prof. Edward J. THOMPSON, of the Institute of Neurology, The National Hospital for Neurology & Neurosurgery, Queen Square, London was approached and he provided access to sera from 53 MS patients, 2 patients with sporadic CJD and 10 patients with viral encephalitis.

In an open study, the 2 sporadic CJD and 10 MS patients had elevated levels of antibodies to Acinetobacter when compared to 12 healthy blood donors. (See figure)



(18) Antibodies to Acinetobacter in MS and M.A.N. assay

In an endeavour to compare these observations, with other neurological diseases, Dr. John CROKER, from the Department of eriatric Medicine at University College Hospital (London) provided 20 sera from patients who had sustained in the preceding twelve months a cerebro-vascular accident or stroke.

A coded study involving 26 MS patients, 20 with strokes and 25 healthy blood donors, showed that only MS patients had elevated levels of antibodies to 5 different strains of Acinetobacter, as well as against Pseudomonas, but not against E.coli.

The results were reported at the XVIIth World Congress of Neurology, which was held in London in June 2001 (Hughes et al., Journal of the Neurological Sciences 2001; 187: PO764, S265).
(Paper 5 in Appendix)

A paper by Hughes et al, describing these results in detail, as well as the use of the M.A.N. index in the diagnosis of MS has appeared in the November 2001 issue of the journal “Clinical & Diagnostic Laboratory Immunology” (2001; Vol.8: 1181-1188) (Paper 6) which is a publication of the American Society of Microbiology.

How such patients acquired antibodies to Acinetobacter is at the moment unclear but MS patients frequently suffer from sinusitis (18) and upper respiratory tract infections (19) and since this saprophytic microbe is found on human skin, inadvertent exposure may have produced such immune responses.

However, the question whether Acinetobacter infections precede or follow onset of MS awaits further studies.








(19A) Conclusions from the MAFF sponsored studies:

(19.1) BSE affected animals have elevated levels of antibodies to Acinetobacter, a microbe which possesses molecular sequences resembling brain tissues and is found in the environment.

(19.2) The origin of these antibodies is at the moment unclear, but it is not beyond the bounds of cautious speculation that Acinetobacter bacteria or antigens were incorporated in the winter feeds of cattle (Meat-and-Bone-Meal = MBM) and thereby evoked these antibodies.

(19.3) BSE affected animals have autoantibodies against both myelin (white matter) and neurofilament (gray matter) components of the brain.

(19.4) If these antibodies were evoked by antigens present in the food materials of cows, then such antibodies should be highest in the mucosal antibody isotype, namely IgA.
The highest levels of anti-Acinetobacter antibodies are present in the mucosal IgA isotype, thereby supporting the hypothesis that such antibodies were produced as a result of antigens present in the food chain and not as the result of brain damage produced by “prions”.

(19.5) This is a powerful argument against the proposition that BSE
damage occurs following exposure to “prions” and the resultant auto-antibodies are a consequence of such damage.
It is difficult to explain why the majority of anti-Acinetobacter antibodies are in the IgA mucosal isotype.

(19.6) It is not clear whether antibodies to Acinetobacter, appeared before or after the onset of BSE.
However one clear conclusion is that when brain homogenates from BSE affected animals are injected into experimental animals, and then they develop a neurological disease, it cannot be said that BSE has been transmitted, unless they also have antibodies to Acinetobacter.
If such anti-Acinetobacter antibodies are not present, then maybe only EAE has been transmitted.



(19B) Conclusions from the MAFF sponsored studies

(19.7) If it can be confirmed that BSE is an autoimmune disease caused by Acinetobacter then it cannot be transmitted by meat consumption, as long as it is hygienically prepared.
This conclusion would appear to be compatible with the extensive nutritional studies carried out by the “National CJD Surveillance Unit” in Edinburgh, who in their yearly reports state that “...the link between meat consumption and v-CJD is less than compelling”.

(19.8) Therefore the public’s fears about the safety of meat consumption could be allayed by publicising these new facts concerning BSE.

(19.9) The culling of healthy animals would appear to be unnecessary, thereby saving substantial amounts of taxpayers’ money.

(19.10) Finally the use of the M.A.N. (Myelin-Acinetobacter-Neurofilament) assay provides a simple ante-mortem test of BSE.
The test could determine whether a cow has BSE before it is sent to a slaughter house and thus prevent its entry into the human food chain.

(19.11) The M.A.N. test could also be used in the diagnosis of MS.














(20) Recommendations:

(20.1) Further studies are required to determine whether antibodies to Acinetobacter species precede or follow the development of clinical disease in BSE affected cattle.

(20.2) This question could be resolved if it could be shown in small experimental animals (mice, rats, guinea pigs or rabbits) that exposure or immunisation with Acinetobacter bacteria or antigens leads to a neurological disease, with development of autoantibodies to both white (myelin) and gray (neurofilaments) brain matter and post-mortem studies show spongiform changes similar to those seen in BSE affected animals.

(20.3) Irrespective of their origin, the measurement of anti-Acinetobacter antibodies, especially in the M.A.N. assay, could be used as an ante-mortem test of BSE, before an animal goes to a slaughter house and thereby prevent its entry into the human food chain.

(20.4) A “reference laboratory” should be set up where such measurements could be carried out and the specific microbiological and immunological tests developed so that veterinarians and other laboratory personnel could be trained in the use of such techniques.

(20.5) King’s College London has both space and research facilities available for such a “reference laboratory”.

(20.6) The costs of setting up such a facility together with staffing involving trained personnel would amount to £ 2 million.

(20.7) In view of the enormous costs so far involved in both BSE together with the human costs of “multiple sclerosis”, the setting up of a research facility which offers hope in tackling both BSE and MS, would appear to be a not too onerous step to take with public resources.






This report is dedicated to the memory of the late Professor John
PIRT, who passed away in the spring of 2000.

During the war he flew with Bomber Command, afterwards he worked for the government at Porton Down and then became Professor of Microbiology, initially at Queen Elizabeth College and later at King’s College.

He strongly supported the work of a microbiological link to autoimmune diseases and appeared before the Phillips Inquiry on
BSE.


20th August 2001



Alan EBRINGER B.Sc, MD, FRCP, FRACP, FRCPath.
Professor of Immunology, King’s College London.

Tel. 020-7848-4302
Fax 020-7848-4500
e-mail alan.ebringer@kcl.ac.uk



Circulation: Government (DEFRA)

Parliament

Principal of King’s College

Public






Acknowledgements
The following have contributed to the work described in this report and their efforts and help were invaluable.

King’s College London

Dr. Clyde WILSON (MAFF) The late Prof. John PIRT
Dr. Harmale TIWANA (MAFF) Dr. Camille ETTELAIE
Ms Lucy HUGHES Ph.D cand. Mr. Phil CUNNINGHAM
Mr Carlos THORPE Dr Sukvinder BANSAL

Wickham Laboratories, Wickham, Hampshire

Dr. William CARTMELL

University of Cambridge

Prof. D.Allen.L. DAVIES

Institute of Neurology, The National Hospital for Neurology and
Neurosurgery, Queen Square

Prof. Edward J. THOMPSON Dr. Viqar CHAMOUN
Dr. Allison GREEN

Department of Geriatric Medicine, University College Hospital

Dr. John CROKER Dr. Judy VOWLES


DEFRA (MAFF)

Dr. David SHANNON Dr. Mandy BAILEY
Dr. Hilary GATES

Central Veterinary Laboratory (Now Central Veterinary Agency)

Mrs. P. HARRIS


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Paper 6