Talks about OSP -A protein found in Lyme disease. The research appears in the latest issue of the Journal of Clinical Microbiology.
Thanks,
grace

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list _uids=15695691&dopt=Abstract

Here is one example of what one group of doctors is testing for. I know that this is for children of autism, but the asumption by this group is that certain forms of autism is auto-immune related.
http://members.jorsm.com/~binstock/tests.htm

IMMUNE PANELS FOR AUTISM SPECTRUM CHILDREN
One Researcher's Observations

--------------------------------------------------------------------------------

by Teresa Binstock
June 1, 1999
My writings do not constitute medical advice.
Instead, they represent a seeking to understand autism-spectrum disorders
and their causes and associated traits.

Introduction

In recent years, biological aspects of autism-spectrum disorders are becoming
documented, researched, and treated. Much of the credit goes to Bernie Rimland
and the DAN! docs, as well as to pioneers such as Paul Shattock, Andy Wakefield,
Bill Shaw, and the persevering folks at the Great Smokies lab -- and to the
parents and interested physicians who ordered lab-tests and who continually
conduct their own research, whether "at home", via PubMed and the Internet, or
via wading into whole-text articles or, in some cases, actually launching
clinical studies (1).

As I survey the growing amount of biological data about autism-spectrum kids,
several categories of biological information are apparent. Generally speaking,
the new data arise from six primary categories of information; there is some
overlap among the categories; and, for most kids whose lab-test data are
available, one major category is missing. Here is a general way to refer to the
6 categories of data already established for autism-spectrum kids:
A. Great Smokies lab data
B. Great Plains lab data
C. IAG data (2)
D. Metabolic analysis, hospital traditional
E. Blood work-up, hospital traditional
F. Neurologist work-ups, CAT, MRI, EEG, etc

What is missing from the above is a *thorough* immune panel akin to what Hugh
Fudenberg, MD, would order, thus making an additional category:
G. *thorough* immune panels
Immunity and infections

I believe that biological aspects of autism-spectrum disorders will not have a
firm foundation until thorough immune-panels become part of the overall
autism-spectrum database (3). Furthermore, for each specific child, the thorough
immune panel may enhance the parents' and physician's understanding of
etiologically significant factors for that specific child; and this knowledge
ought augment avoiding treatments that may be harmful while aiding in the design
of positive treatments for that child.

At the Orlando conference (4), the importance of immune and infectious
contributions was conveyed most clearly by Dr. Luigina Romani, who focused upon
immune- and infection-related factors that can shift immunity and thereby
contribute to persistent or recurring Candida -- an infection that not only is
worthy of treating but also is a symptom of the underlying immune shift whose
symptoms, signs, and causes need be addressed. Her lecture complemented my own
interest and early findings in immunological and infectious profiles of
autism-spectrum children.

In recent years a parents of autism-spectrum kids have been sending me the
child's immune-panel, often accompanied by other lab reports, occasionally
including an entire medical history. As previously mentioned, the most thorough
immune panels were ordered by Hugh Fudenberg, MD (5); and most of these reports
demonstrate at least one, often two, and occasionally three signs of atypical
chronic infection and/or immune atypicality. Importantly, these infectious and
immunological signs cannot be identified and delineated by data-sets A thru F
in the above list. Instead, to fully comprehend the biological aspects of many
(probably most, I'd now say) autism-spectrum kids, immune-panel data are
necessary.
Why obtain data about immunity and infections
Rationale

(i) My readings of thorough immune panels of autism-spectrum have revealed
that most such lab reports indicate one or several infectious and/or immune
atypicalities.

(ii) Consistent with my research the last several years, VK Singh, PhD,
and Andy Wakefield, MD, now talk about the viral lesions that accompanied or
preceeded subsequent problems -- whether vaccination-induced neuropathies or
post-infection autoimmunity (1). Importantly, just as Reed P. Warren, Alma
Maciulis, and Roger Burger documented specific, mild genetic mutations in a
percentage of autism-spectrum kids, so too has recent research shown that
impaired immunity can be induced by chronic infections (6).

(iii) The one set of genes positively associated with a large number of
autism-spectrum kids involves null alleles of Complement 4b along with, in many
null-C4b-allele individuals, an extended immune-weakening genomic DNA segment
(extended haplotype); These findings implicate infectious processes as
etiologically significant in many cases of autism, whether in the mother and/or
in the fetus, neonate, infant, or toddler.

(iv) Certain of these viruses live forever within humans, but most of us do
not create the atypical antibodies levels seen in the autism-spectrum charts
I've perused. In other words, not only does the child have the ongoing presence
of a given virus or several, but he or she is having a chronic problem with how
his or her body is responding to that virus. Furthemore, when this occurs, the
child may well have other immune dysregulations as well -- which is also
apparent in a goodly proportion of the thorough immune panels I've perused.

(v) Dr. Romani's data point in a similar direction, ie, a person with
persistent Candida infections is likely to have an immune shift in a Th2
direction -- which is what some pathogens can do. Furthermore, whereas
persistent Candida is important, it is the tip of the iceberg, and represents
the fact that an immune-system altered in a Th2 direction is likely (6-7).
However, categories A thru F do not provide data for unraveling this mystery in
a specific child. Only Category G tests -- a thorough immune panel -- provide
that data.

(vi) Regressions within the autism-spectrum suggest that the neurological
basis of the child's traits is not hardwired and is being affected by internal
changes. One possibility is that, in *some* cases a viral re-activation from
latency is the culprit; and again, categories A thru F are not very helpful in
determining the likelihood of chronic, atypical infections and underlying immune
shifts (8).
[Here it is important to note that Bill Shaw's Great Plains lab is
now offering a number of immune-related tests, and immune tests not
offered by Bill and crew can be obtained by other labs (9)]
Overview
Because *most* of the thorough immune panels I've perused contain obvious
atypicalities (10a), and because the work of Reed Warren, Roger Burger and
others implicates infectious etiologies and immune aspects as significant, I
believe that, for many autism-spectrum children (10b-10i), a thorough list of
initial immune-panel tests is needed.
What immune tests?
Parents occasionally query the autism-list and other lists asking "What immune
tests?" My suggested answer to that question emerges as follows: in a high
percentage of kids representing the still small number of immune panels I've
perused, *nearly *every *child has signs of a percolating infection or several,
far beyond reference ranges. The words underlying, chronic, and atypical are
appropriate. In several cases these elevations are accompanied by an obvious
immune impairment, eg, no response to a common antigen such as tetanus, mumps,
or varicella. That these atypicalities occur suggests that information from a
thorough immune panel is extremely important for many and perhaps most autism-
spectrum children and would augment their treatment protocols if and as
significant data are obtained.

In the context of credit due Hugh Fudenberg, Reed Warren, and VK Singh, an
immune-panel my research shows to be significant is presented below.
Initial and long-term use
By presenting a comprehensive list of immune-panel tests, parents and
cooperative docs can have a useful starting point for evaluating an
autism-spectrum child. Later, if and as biological treatments are enacted, the
initial test data will provide a baseline measure for evaluating subsequent
therapies.
Resolving an irony
That biological analyses of autism-spectrum kids usually have not included
Fudenberg-like immune panels is ironic, given that the Reed Warren et al
findings about immune-impairments in autism-spectrum children have been known
for so long.

In other words, if these kids have acquired and/or genetic immune-impairments,
let's evaluate their viral load and their immune function -- along with the
Category A thru F measures already pioneered; and I can't help but think that,
in some and perhaps many autism-spectrum kids, the atypicalities measured by
Great Smokies, Great Plains, and other labs may well be due to some of the same
viral critters and immune-shifts I'm noticing in the Fudenberg-like panels I've
seen thus far.
My concern about steroids such as Prednisone
Many autism-spectrum and/or LKS kids are prescribed steroids such as Prednisone,
which many parents describe as "it really helped, for a while" and/or "my
child's deterioration occurred while on Prednisone".

Importantly, Prednisone is known to be an immune suppressant. Based upon what
I've seen in the through immune panels I've perused, I no longer know how a
neurologist or other doctor can dare to prescribe Prednisone without first
ordering an extensive immune/infectious workup that would indicate whether or
not any infectious and/or immune atypicalities are present, especially given the
increasingly documented link between certain pathogens and seizures. For
instance, Herpes simplex virus (HSV) is now implicated in a goodly percentage
of seizure disorders (eg, 11-13); and Predisone's immunosuppressive effects are
well known (14).
Bottom line
My opinion as a non-MD researcher is that, for autism-spectrum kid, category G
hereinabove -- the thorough immune panel -- needs be obtained by parents and
docs. Will the thorough immune panel offer clues for every child? Probably not,
but the only way to determine that is to obtain and evaluate the results of the
data.

Immune panel data augment findings from the other categories of lab data, and
vice versa. Without the thorough immune panel, the pilot is flying with a high
degree of blindness.
A Basic Immune Panel for Autism Diagnostics
Review of initial findings

In most *thorough* immune-panel reports that I've perused on behalf of parents
of autism-spectrum kids (n<15), tests in the Basic Panel have revealed atypical
elevations of EBV, CMV, and/or HHV6; co-occurring infections are common; and
other immune atypicalities are seen in some of the panels, including -- even in
this small initial sampling and with much variation from child to child:
(a) atypically high elevations of vaccinal antigens or measles,
(b) mild elevations that may reflect adjuvant effects from other antigens or
pathogens such as EBV,
(c) non-detected antibodies against a vaccinal antigen (eg, tetanus, varicella,
mumps),
(d) increased or decreased numbers of Natural Killer cells,
(e) impaired NK function,
(f) atypical elevations of certain cytokines,
(g) altered ratios of T cell subsets, and
(h) occasional skewing of the child's immunoglobulin levels.
Cavaet
If a parent purchases a thorough immune evaluation, he or she is not guaranteed
that meaningful results will come forth. There is no way of knowing what the
tests will show, although the child's and the family's medical history can
provide clues as to what tests ought not be omitted. For some parents, the money
invested in the tests will have been wasted. Furthermore, the data from such an
immune panel may place the child and the parents at the forefront of medical
research and treatment, which means that data and observations from recent
research will have to be utilized (5, 12a-12b).
The Basic Immune-Panel
At one prominent lab, tests constituting what I think of as the "Basic Panel"
would cost slightly less than $1500.

The following list sets forth a minimum of tests I believe necessary for an
initial evaluation of the child's immunity. There is an emphasis upon herpes
class viruses because (i) they are ubiquitous, (ii) they impair immunity, and
(iii) most panels I've perused on behalf of autism-spectrum children report
atypical elevations of antibodies against one or several of these viruses.

A viral screen is important, especially for IgG antibodies, which would indicate
an atypical chronic infection. EBV provides an exception, because it has a
variety of proteins that, if reactivated, can generate IgM antibodies; thus for
EBV, both IgM and IgG are suggested. Also, if the child has recently experienced
a regression, then adding IgM antibodies might be instructive in some cases.

IgG HSV1, HSV2, varicella, CMV, HHV6
IgM and IgG for an EBV screen
IgG measles
IgG rubella
IgG rubeola
IgG coxsackie

IgG vaccinal antigens, eg,
diptheria, tetanus, mumps
IgG for Myelin Basic Protein (16)

total immunoglobulins by category
complement levels/function
secretory IgA (saliva)
thyroid panel: T3, T4, T3 uptake, FTI, TSH, and TRH
The TRH measurement is not traditional but
appears to be a very important measurement in
autism-spectrum kids.

The following is offered as a set of tests and mimics much of the
data presented in the charts I've evaluated:

Tests which are not antigen-specific:
Total T, B lymphocytes
T4/T8 Helper Suppressor Ratio
Activated T Cells
NK count
NK activity
Lymphocyte Immune Function Test (T and B)
In addition to the basic panel
The tests listed above provide an excellent overview of many aspects of the
child's immunity. However, pathogen-specific assays are *specific*, ie, they
don't provide information about other pathogens. However, the last six tests
listed above provide an overview that can reflect pathogens not studied in the
pathogen-specific tests.

Nice additions, as appropriate ($750 or less, total)
microflora panel
parasites panel
fungal panel
monocyte/macrophage function
IgG anti-serotonin antibodies
IgG anti-dopamine antibodies

More nice additions
DR CD38 CD45 CDRO
cytokines
IgG subclasses
T-helper 1,2 function
papilloma (PCR of warts)

Case history particulars might suggest from among:
anti-cardiolipin IgM, IgA, IgG
IgE analyses
food panel
In closing
The work of numerous researchers, augmented and expanded by the immunity and
infection lab-tests ordered by a few physicians, demonstrate that immune-
impairments (whether acquired and/or genetic) appear to play a causal and (in
some cases) an ongoing role in a goodly subset of autism-spectrum children. The
information from a thorough immune panel is an important contribution to a
child's diagnostic profile and treatment options.
References
1. Bolte ER. Autism and Clostridium tetani. Med Hypotheses 1998 51(2):133-44.

2. Paul Shattock and colleagues have been finding atypical IAG levels in a
substantial percentage of autism-spectrum children. Here is a preliminary
citation about their work:

J Chromatogr B Biomed Sci Appl 1998 Aug 7;712(1-2):51-8
Rapid analysis of low levels of indolyl-3-acryloylglycine in human urine by
high-performance liquid chromatography.
Mills MJ, Savery D, Shattock PE
Autism Research Unit, School of Health Sciences, University
of Sunderland, UK.

3. Hugh Fudenberg, MD, is one of the 20th Century's preeminent immunologists.
Immune panels ordered by Dr. Fudenberg are the examples I have in mind when I
write the phrase "thorough immune panels".

4. Biological Treatments for Autism and PDD. Orlando Conference, May 8-9, 1999.

5. Fudenberg HH. Dialysable lymphocyte extract (DLyE) in infantile onset autism:
a pilot study. Biotherapy 1996;9(1-3):143-7.
Neurolmmuno Therapeutics Research Foundation Spartanburg,
S.C., USA.
ab: 40 infantile autistic patients were studied. They ranged from 6 years to
15 years of age at entry. 22 were cases of classical infantile autism; whereas
18 lacked one or more clinical defects associated with infantile autism
("pseudo-autism"). Of the 22 with classic autism, 21 responded to transfer
factor (TF) treatment by gaining at least 2 points in symptoms severity score
average (SSSA); and 10 became normal in that they were main-streamed in school
and clinical characteristics were fully normalized. Of the 18 remaining, 4
responded to TF, some to other therapies. After cessation of TF therapy, 5 in
the autistic group and 3 of the pseudo-autistic group regressed, but they did
not drop as low as baseline levels.
PMID: 8993773, UI: 97146917

6. Puccetti P, Romani L, Bistoni F. A TH1-TH2-like switch in candidiasis: new
perspectives for therapy. Trends Microbiol 1995 Jun;3(6):237-40.

7. Romani L et al. T helper cell dichotomy to Candida albicans: implications for
pathology, therapy, and vaccine design. Immunol Res 1995;14(2):148-62.

8. acquired immune-impairment monograph

9. Four labs among many:
Antibody Assays Laboratory
Great Plains Laboratory
Immunosciences Lab Inc
Lab of VK Singh, PhD, c/o U of Michigan

10a. atypical chronic infection in autism-spectrum children:
chronic infection

10b. Warren RP, Odell JD, Warren WL, Burger RA, Maciulis A et al. Strong
association of the third hypervariable region of HLA-DR beta 1 with autism. J
Neuroimmunol 1996 Jul;67(2):97-102.
Center for Persons with Disabilities, Utah State
University, Logan 84322, USA. [email protected]
10c. Warren RP et al. Immunogenetic studies in autism and related disorders.
Mol Chem Neuropathol 1996 May-Aug;28(1-3):77-81
10d. Warren RP, Yonk J, Burger RW, Odell D, Warren WL. DR-positive T cells in
autism: association with decreased plasma levels of the complement C4B protein.
Neuropsychobiology 1995;31(2):53-7.
10e. Warren RP, Burger RA, Odell D, Torres AR, Warren WL. Decreased plasma
concentrations of the C4B complement protein in autism. Arch Pediatr Adolesc Med
1994 Feb;148(2):180-3.
10f. Warren RP et al. Increased frequency of the null allele at the complement
C4b locus in autism. Clin Exp Immunol 1991 Mar;83(3):438-40.
10g. Yonk LJ, Warren RP, Burger RA et al. CD4+ helper T cell depression in
autism. Immunol Lett 1990 Sep;25(4):341-5.
10h. Warren RP et al. Deficiency of suppressor-inducer (CD4+CD45RA+) T cells in
autism. Immunol Invest 1990 Jun;19(3):245-51.
10i. Warren RP, Foster A, Margaretten NC. Reduced natural killer cell activity
in autism. J Am Acad Child Adolesc Psychiatry 1987 May;26(3):333-5.
10j. Warren RP et al. Immune abnormalities in patients with autism. J Autism Dev
Disord 1986 Jun;16(2):189-97.
ab: We have begun an investigation on the immune systems of patients with
autism in attempt to determine if immune mechanisms are involved in the
development of this severe developmental disorder. A study of 31 autistic
patients has revealed several immune-system abnormalities, including reduced
responsiveness in the lymphocyte blastogenesis assay to phytohemagglutinin,
concanavalin A, and pokeweed mitogen; decreased numbers of T lymphocytes; and
an altered ratio of helper to suppressor T cells...

11. Sanders VJ et al. Presence of herpes simplex DNA in surgical tissue
from human epileptic seizure foci detected by polymerase chain reaction:
preliminary study. Archives of Neurology 54.8.954-60 1997.

12. Cornford ME, McCormick GF. Adult-onset temporal lobe epilepsy associated
with smoldering herpes simplex 2 infection. Neurology 1997 Feb;48(2):425-30.
ab: A 40-year-old man with chronic genital herpes simplex infection
developed partial complex temporal lobe seizures of insidious onset, with EEG
and MRI evidence of a unilateral temporal lobe destructive, atrophic process.
Extensive workup did not reveal an infectious etiology. Three years of
escalating number and severity of daily seizures with memory loss led to
temporal lobectomy. Histologic study revealed active, low-level viral infection
in the resected hippocampus and temporal lobe cortex, with immunohistochemical
evidence for infection by herpes simplex 2, principally in neurons. In situ
hybridization confirmed the presence of herpes simplex virus in neurons.
Anticonvulsant-resistant seizure episodes began to recur several times daily
soon after surgery, but the addition of acyclovir to the treatment regimen
resulted in a substantial reduction in seizure occurrence, maintained for the
subsequent 2.5 years.

12b. Kitchingman GR, Rooney C. Cytotoxic T cells and immunotherapy. Pediatr
Radiol 1998 Jul;28(7):489-91.
Department of Virology and Molecular Biology, St. Jude
Children's Research Hospital, 332 N. Lauderdale St.,
Memphis, TN 38105, USA.
ab: Promising immunotherapies for viral infections and malignancies reflect the
successful, rapid translation of laboratory findings into clinical practice.
Fletcher et al. [1] present imaging studies of Epstein-Barr virus
(EBV)-associated lymphomas before and after immunotherapy. Here, we briefly
review the scientific bases of such novel therapies, which have evolved from
advances in understanding of immune effector cells, of the cytokines that drive
immune responses, and of the mechanisms underlying cell death.

13. Neurologic aspects of Herpes simplex virus:
neurologic HSV

14. Steroids as immunosuppressants:
steroids

15. Kitchingman GR, Rooney C. Cytotoxic T cells and immunotherapy. Pediatr
Radiol 1998 Jul;28(7):489-91.
Department of Virology and Molecular Biology, St. Jude
Children's Research Hospital, 332 N. Lauderdale St.,
Memphis, TN 38105, USA.
ab: Promising immunotherapies for viral infections and malignancies reflect the
successful, rapid translation of laboratory findings into clinical practice.
Fletcher et al. [1] present imaging studies of Epstein-Barr virus
(EBV)-associated lymphomas before and after immunotherapy. Here, we briefly
review the scientific bases of such novel therapies, which have evolved from
advances in understanding of immune effector cells, of the cytokines that drive
immune responses, and of the mechanisms underlying cell death.
Comment on: Pediatr Radiol 1998 Jul;28(7):492-6

16. VK Singh, PhD, is among the pioneers of autoimmune aspects of autism-
spectrum disorders. His lab offers several assays, including anti-MBP
antibodies. His lab is currently providing several assays significant in autism
spectrum children, including but not limited to anti-MBP antibodies, anti-
measles antibodies, etc. Here are *some* of his published articles: