This is what I been saying! Dr K believes it can do this by moleculr mimicry. He says this should be obvious since the lyme vaccine, which uses lyme proteins, was causing autoimmunity (most likely by way of molecular mimicry with human protein myosin), and there's no active infection there...
Here's his testimony to United States Congress, its worth a read. He is very sharp.
https://www.govinfo.gov/content/pkg/chrg-112shrg75786/html/chrg-112shrg75786.htm Section of the Statement of Amiram Katz, M.D. to congress:
If after the infections are identified and treated adequately the
patient continues to be symptomatic, there are two main processes that
can explain the patient's condition:
1. Residual damage from either of the above (e.g. brain damage
resulting in white matter lesions leading to permanent neurologic
deficits).
2. The post-Lyme autoimmune syndrome is probably the most common
cause for the chronic illness, the rheumatologic aspects of which were
described in the literature over 20 years ago (Steere, et al.
Association of chronic Lyme arthritis with HLA-DR4 and HLA-DR2 alleles.
NEJM. 1990; 323:219-23. Steere, et al. Autoimmune mechanisms in
antibiotic treatment-resistant Lyme arthritis. JAI. 2001; 16:263-66).
It was also shown by Aledini and Latov that ``Antibodies against
OSPA epitops of Borrelia burgdorferi cross react with neuronal tissue''
(Journal of Neuroimmunology. 2005; 159:192-95) explaining why the post-
Lyme autoimmune syndrome is not only a rheumatological condition, but
also a neurological.
Under the autoimmune category, the post-Lyme vaccination syndrome
should be included (Latov, et al.--Neuropathy and cognitive impairment
following vaccination with the OSPA protein of Borrelia burgdorferi. J
Periph Ner Sys 2004;9:165-67).
A different group of researchers showed that Osp-A shares similar
amino acid sequence with the streptococcal protein M, that is similar
to a human muscle protein, myosin, that triggers human autoimmune
conditions such as carditis (disease of the heart), arthritis and
possibly other post-streptococcal conditions (Raveche, et al. Evidence
of Borrelia autoimmunity-induced component of Lyme carditis and
arthritis. J Clin Microb. 2005;43:850-56).
The recent collaboration between Latov, Aledini, Wormser and
Klempner (who was the PI of the extramural NIH ``chronic'' Lyme study
in the late 1990s--Klempner, et al. Two controlled trials of antibiotic
treatment in patients with persistent symptoms and a history of Lyme
disease. NEJM 2001;345:85-92), showed that the sera of patients with
``chronic'' Lyme disease contain anti-neuronal antibodies (Chandra, et
al. Anti-neural antibody reactivity in patients with a history of Lyme
borreliosis and persistent symptoms. Brain Behav Imm. 2010;24:1018-24).
Recent studies of proteomic patterns (a test for the patterns of
protein components) generated by the cerebrospinal fluids of patients
with ``chronic'' Lyme further supports that this disease entity is
unique and cannot be ``lumped'' with other syndromes (Schutzer, S. E.,
et al. Distinct cerebrospinal fluid proteomes differentiate post-
treatment Lyme disease from chronic fatigue syndrome. Plos One 2011;6:
e17287).
In the past 3 years, we have found that many patients with
``chronic'' Lyme disease exhibit anti-neuronal antibodies and increased
Cam II kinase activity (antibody mediated neuronal damage via calcium
channel activation), as found in Dr. Cunningham's laboratory at the
University of Oklahoma (Kirvan, et al. Mimicry and autoantibody-
mediated neuronal cell signaling in Sydenham chorea. Nature Med.
2003;9:914-20), supporting, again, the autoimmune nature of ``chronic''
Lyme.
We found that both the peripheral and central nervous system are
targeted in post-Lyme and post-Lyme vaccine illnesses. Unlike the known
autoimmune nature of demyelinating neuropathy of large fibers, many of
those patients experience immune neuropathies of sensory and autonomic
ganglia.
Treatment
When facing ``chronic'' Lyme, with an autoimmune flavor, one should
consider treatment with a combination of hydroxy chloroquine and a
macrolide.
HYDROXYCHLOROQUINE + MACROLIDES
The rationale of the treatment is:
1. The hydroxychloroquine potentates the antibiotic effects of
macrolides, by increasing the pH in the lysosome (``Late and chronic
Lyme disease'', Sam Donta. Medical Clinics of North America 2002; 86:
341-49. ``Macrolide therapy of chronic Lyme disease,'' Sam Donta.
Medical Science Monitoring, 2003; 9(11):136-42).
2. Hydroxychloroquine has also immune modulating properties and is
classified as a weak DMARD (disease modifying anti-rheumatic drug). It
interferes with the functioning of T- and B-Lymphocytes, monocytes and
macrophages by entering their lysosomes and increasing the lysosomal
pH, which inhibits the ability of these cells to produce and release
inflammatory cytokines and hydrolytic enzymes.
Clarithromycin possesses anti-inflammatory properties and
potentiates the effects of hydroxychloroquine. I have seen many
patients with intractable arthritis improve when macrolides are added
(``Anti-inflammatory activity of macrolide antibiotics.'' The Journal
of Pharmacology and Experimental Therapeutics. January 2000, 156-63;
Ianaro, et al.).
Immune modulation and anti-inflammatory properties are especially
advantageous in the setting of post-Lyme autoimmune syndrome.
3. The combination of an anti-malarial and a macrolide treats
Babesia, a common co-infection ``Atovaquone and azithromycin for the
treatment of Babesioses'' Krause, et al. New England Journal of
Medicine 2000; 343: 1454-58).
BENZANTHINE PENICILLIN
When hydroxychloroquine/macrolide combination is not effective,
cannot be tolerated (allergic reactions, GI side effects, tinnitus,
contact dermatitis, psoriasis flair up, ophthalmologic
contraindications, etc.), or when hydroxychloroquine has reached its
maximal safe cumulative dosage (1,000G)--intramuscular benzanthine G
penicillin (Bicillin LA) is an option (Marco AC and Accrdo S. Long-term
treatment of chronic Lyme disease with benzanthine penicillin. Ann
Rheumat Dis 1992;51:1007-08).
The mechanism of action of benzanthine penicillin (other than the
obvious antimicrobial) is unknown. Why 3 percent of the daily
intravenous dose of penicillin can achieve much better results when
injected intramuscularly once a week?
One explanation is that the bacteriocidal signal it sends is not
strong enough to activate defense mechanisms of the spirochete, but
enough to suppress the expression of the outer surface proteins (mainly
OspA and OspB) which are known to trigger inflammation (Rupprecht, et
al. The pathogenesis of Lyme neuroborreliosis: from infection to
inflammation. Molecular Medicine. 2008;14:205-12).
Another explanation is that Bicillin is an effective anti-
streptococcal treatment and that the autoimmune morbidity is
perpetuated by streptococcal presence.
I have had a significant number of patients with Chronic Lyme
disease who did not get better on long courses of oral and/or
intravenous antibiotics, but responded to weekly Bicillin shots within
a month or two. This treatment is so benign, that I offer it now prior
to hydroxychloroquine and clarithromycin, in spite of its poorly
explained mechanism of action.
INTRAVENOUS IMMUNOGLOBULINS (IVIG)
Are not indicated for the treatment of Lyme disease per se. They
are indicated when there is immune deficiency or neurologic conditions
of autoimmune nature complicating Lyme disease.
Autoimmune diseases affect about
5 percent of individuals in
developed countries. Autoimmunity is the patho-physiologic mechanism in
neurologic conditions affecting the myelin of the peripheral and
central nervous system, the basal ganglia, the post-synaptic membrane,
the hippocampal pyramidal cells and Purkinje cells, among other
targets, in a variety of autoimmune conditions of the nervous system.
Autoimmunity is believed to be a result of complex interactions
between genetic traits and environmental factors. Infections and
vaccinations are some of the more known environmental factors. Among
other known mechanisms are myeloprolif-
erative conditions and other neoplasms (through a paraneoplastic
mechanism).
The outer surface protein A of Borrelia burgdorferi (OspA) is a
lipoprotein with a molecular weight of 31kd that possesses immuno-
stimulatory properties that can activate pro-inflammatory toll-like
receptors of the immune system. Receptors of this kind are also
expressed in a variety of neuronal elements including Schwan cells,
microglia, asrtocytes and oligodendroglia, which probably contribute to
the development of inflammatory responses affecting the entire nervous
system. The OspA has a partial amino acid sequence (165-73) homologous
to that of HLFA-1 (human lymphocytic function associated antigen-1)
that results in activation of T cells to this auto antigen ending in an
autoimmune disease (autoimmune disease caused by ``molecular mimicry''
mechanism).
As discussed earlier, it was shown that certain sequence of amino
acids on the OspA can trigger the formation of anti-neuronal
autoantibodies (Aledini and Latov. Antibodies against OSPA epitops of
Borrelia burgdorferi cross react with neuronal tissue. Journal of
Neuroimmunology. 2005; 159:192-95). Osp-A shares similar amino acid
sequence to the streptococcal protein M, that is similar to myosin and
triggers immune carditis, arthritis and even Sydenham's chorea
(Raveche, et al. Evidence of Borrelia autoimmunity-induced component of
Lyme carditis and arthritis. J Clin Microb. 2005;43:850-56).
Both Lyme disease and the Lyme vaccine (LYMErix--Latov, et al.--
Neuropathy and cognitive impairment following vaccination with the OSPA
protein of Borrelia burgdorferi. J Periph Ner Sys 2004;9:165-67) can
trigger neurologic autoimmune disease. Since the Lyme vaccine is a pure
preparation of OspA (coated onto aluminum hydroxide), it is reasonable
to assume that this protein is also responsible for the autoimmune
disease triggered by Lyme infection. This autoimmune disease is
especially common in individuals with class II, MHC HLA DR4
(DRB1*0401), whose macrophages identify the amino acid sequence shared
by the OspA and our body proteins as ``non-self '' attach to it and
present it to the T & B lymphocytes.
Persisting presence of IgM antibodies reacting to the OspA, which
is not reported by common laboratories (Western Blot band 31), might be
an indicator of an autoimmune condition triggered by this protein. The
fact that patients with this condition have a disease of both
peripheral and central myelin, also supports the etiology (post-Lyme/
LYMErix autoimmune), since it is uncommon for patients with ``pure''
MS, who have a disease of the central myelin, to have peripheral
neuropathy. And vice versa, it is uncommon to have MS when having
demyelinating neuropathy.
The most common Lyme associated autoimmune conditions affecting the
central and peripheral nervous system myelin result in ``white matter
lesions'' on brain MRI's which are associated with a wide range of
neuropsychiatric manifestations; damage to the basal ganglia/sub
thalamic nucleus resulting in bizarre and disabling movement disorders
and; peripheral nerve conditions such as Guillain Barre, CIDP and even
multifocal motor neuropathy with block, but more frequently
ganglioneuropathy of the sensory and autonomic nerves.
Intravenous immunoglobulins (IVIG) are widely used for treatment of
a variety of diseases, but mainly in autoimmune neurologic conditions
(Dalakas MC. Intravenous immunoglobulin in autoimmune neuromuscular
diseases. JAMA. 291:
2367-75, 2004).
Their exact mechanism of their action is unknown, but there are
several possibilities:
a. They probably bind to the idiotypes via their anti-idiotypic
variable portion, blocking the interactions between the idiotypes and
idiotypic antigens that usually lead to autoimmune disease.
b. IVIG bind to the Fc receptors of the macrophages preventing
phagocytosis and to the Fc receptors of the autoantibodies in the
antigen-antibody complex, preventing activation of the complement.
c. They bind to the C3 complement fraction and impeding the
complement cascade.
The major advantage of IVIG therapy is achieving significant
immunomodulation with arrest of the autoimmune process, which is
comparable to high dose steroids or cytotoxic agents, without
immunosuppression and its associated risks.
In multiple sclerosis, the effects of beta-interferons on
susceptibility to infections are not clear. By modifying the host
inflammatory response they can impair the body's ability to fight
infection. The recent natalizumab (Tysarbi) experience (Warnke, et al.
Natalizumab and Progressive Multifocal Leukoencephalopathy. Arch Neur.
2010; 67:923-930) showed that the only two patients receiving
natalizumab that developed PML (progressive multi focal
leukoencephalopathy), where those also receiving Avonex (beta-
interferon 1-alpha). This means that the beta interferons are not so
safe when patients have an ongoing infection.
Our view is that in conditions where autoimmune processes are
linked to infections and it is not clear whether the infection is
active or not, IVIG treatment should be tried first. High dose steroids
and/or immunosuppressive agents should be considered as a treatment
option only when IVIG fail, or contraindicated.
Selected Publications on the Topic
Grzegorz S. Nowakowski, M.D.; and Amiram Katz, M Epilepsia partialis
continua as an atypical presentation of cat scratch disease in a
young adult. NEUROLOGY 2002;59:1815-16.
Katz A. IVIG treatment in patients with Lyme associated movement
disorder Autoimm Rev. 2006;15:106-09.
Katz A. IVIG treatment in patients with Lyme and demyelinating disease.
Autoimm Rev. 2006;15:302-05.
Katz A, Zubal G, Westerveldt M, Blumenfeld H and Seibyl J.
Neuropsychological Testing and SPECT/PET Ratio-Images In Patients
with Lyme Encephalopathy--Pre- and Post-Antibiotic Treatment
Studies. JOI. 2007;17:103.
Katz, A and Berkley JM. Diminished Epidermal Nerve Fiber Density in
Patients with Antibodies to Outer Surface Protein A (OspA) of B.
burgdorferi Improves with Intravenous Immunoglobulin Therapy.
Neurology 2009;72(S3):A55.
Milone M, Katz A, Amato AA, et al. Sporadic late onset nemaline
myopathy responsive to IVIG and immunotherapy. Muscle & Nerve.
2010;41:272-76.
Senator Blumenthal. Thank you.
[Applause.]
Dr. Petrini.
Post Edited (dcd2103) : 2/2/2021 11:18:53 AM (GMT-7)