Antibodies to heparan sulfate glycosaminoglycans in the...

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...

Reexamination Certificate

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C436S501000, C436S503000, C436S506000, C436S507000, C436S513000, C424S130100, C424S137100

Reexamination Certificate

active

06228598

ABSTRACT:

BACKGROUND OF THE INVENTION
Guillain-Barré syndrome (GBS) is an acute, immune-mediated, motor-sensory polyneuropathy (AIP) that typically has evidence of demyelination on electrodiagnostic or pathological studies (Asbury, A. K., and McKhann, G. M.,
Ann. Neurol
41:287-288 (1997); Asbury, A. K., and Comblath, D. R.,
Ann. Neurol.
27suppl:S21-4 (1990)). Other AIP syndromes have selective motor (McKhann, G. M. et al.,
Ann. Neurol.
33:333-342 (1993)), cranial nerve (Fisher, M.,
N. Engl. J. Med.
255:57-65 (1956)), or axonal involvement (Feasby, T. E. et al.,
Brain
109:1115-1126 (1986)). In acute motor axonal neuropathy (AMAN) (Kornberg, A. J. and Pestronk, A.,
Muscle Nerve
17:100-104 (1994)) and Miller-Fisher syndrome (Chiba, A. et al.,
Ann. Neurol.
31:677-679 (1992)), antibodies directed against neural antigens, such as glycolipids, have been reported in 30% to 90% of patients; however, serum antibodies, with some disease specificity and directed against purified neural antigens, have not been consistently identified in most motor-sensory GBS syndromes with demyelinating features (Hartung, H. P. et al.,
Muscle Nerve
18:137-153 (1995); Rostami, A. M.,
Spring. Semin. Immunopathol.
17:29-42 (1995); Vriesendorp, F. J. et al.,
Ann. Nerol.
34:130-135 (1993); Ilyas, A. A. et al.,
Ann. Neurol.
23:440-447 (1988); Willison, H. J. and Kennedy, P. G.,
J. Neuroimmunol.
46:105-112 (1993)).
Because polyneuropathies are potentially treatable, correct identification of a patient's particular polyneuropathies is important. Methods of diagnosing such polyneuropathies based on specific disease-related criteria would facilitate identification of treatable disease and expedite commencement of treatment.
SUMMARY OF THE INVENTION
The current invention pertains to methods for diagnosing, in an individual, certain immune-mediated, motor-sensory polyneuropathies (MSP), particularly Guillain-Barré syndrome (GBS); chronic demyelinating polyneuropathy having an acute, GBS-like onset; multifocal motor neuropathy (MMN); polyneuropathy with serum IgM M protein; or polyneuropathy with antibodies to myelin-associate glycoprotein (MAG). The methods include assaying a test sample of bodily fluid, blood, serum or other tissue from an individual for the presence of antibodies, such as IgM or IgG antibodies, that bind to a heparan sulfate glycosaminoglycan or to an acetylated heparan sulfate glycosaminoglycan. In the methods, a heparan sulfate glycosaminoglycan sample, which can include a protein having a heparan sulfate glycosaminoglycan chain or heparan sulfate glycosaminoglycan that is not associated with a protein, and which can include acetylated heparan sulfate glycosaminoglycan or non-acetylated heparan sulfate glycosaminoglycan, is contacted with the test sample. The amount of antibody that binds to the heparan sulfate glycosaminoglycan is then assessed and compared to a reference amount, or to the amount of anti-heparan sulfate glycosaminoglycan antibody in at least one negative control sample of a comparable bodily fluid or tissue. The presence of MSP is indicated by an amount of anti-heparan sulfate glycosaminoglycan antibody that is greater than a reference amount, or by an amount of anti-heparan sulfate glycosaminoglycan antibody that is significantly greater (e.g., that is at least three standard deviations greater) in the test sample than in the negative control sample(s). In a preferred embodiment, the titer of the antibody that binds to the heparan sulfate glycosaminoglycan is assessed and compared to the titer of anti-heparan sulfate glycosaminoglycan antibody in a negative control sample of a comparable bodily fluid or tissue. If titer is used, a titer of IgM antibody in the test sample that is at least about 5,000 greater than the titer in a negative control sample, or a titer of IgG antibody in the test sample that is at least about 12,000 greater than the titer in a negative control sample, is indicative of the presence of the immune-mediated, motor-sensory polyneuropathy (MSP).
The methods of the invention use disease-specific criteria to identify the presence of certain immune-related motor-sensory polyneuropathies, and thus allow identification of disease even in the presence of varying clinical manifestations of the disease. Identification of the particular disease allows early intervention for treatment of disease and appropriate management of disease symptoms.


REFERENCES:
Terryberry, J. W. et al.,Neurobiology of Aging, 19(3): 205-216, May 1998.*
Fredman, P. et al., “Antibodies in sera from patients with inflammatory demyelinating polyradiculoneuropathy react with ganglioside LM1 and sulphatide of peripheral nerve myelin,”J. Neurol.238: 75-79 (1991).
Vriesendorp, F.J. et al., “Serum antibodies to GM1, GD1b, peripheral nerve myelin, and Campylobacterjejuni in patients with Guillain-Barre syndrome and controls: correlation and prognosis,”Ann. Neurol.34:130-135 (1993).
Willison, H.J. and Kennedy, P.G., “Gangliosides and bacterial toxins in Guillain-Barre syndrome,”J. Neuroimmunol46:105-112 (1993).
Gilburd, B. et al., “Autoantibodies to phospholipids and brain extract in patients with the Guillain-Barre syndrome: cross-reactive or pathogenic?, ”Autoimmunity16;23-27 (1993).
Hafer-Macko, C.E. et al., “Immune attack on the Schwann cell surface in acute inflammatory demyelinating polyneuropathy,”Ann. Neurol.39:625-635 (1996).
Hartung, H.P. et al., “Immunopathogenesis and treatment of the Guillain-Barre syndrome-part I.,”Muscle Nerve18:137-153 (1995).
Ilyas, A.A. et al., “Serum antibodies to gangliosides in Guillain-Barre syndrome,”Ann. Neurol.23:440-447 (1988).
Kusunoki, S. et al., “No-acetylgalactosaminyl GD1a is a target molecule for serum antibody in Guillain-Barre syndrome,”Ann. Neurol.35:570-576 (1994).
Pestronk, A. and Choski, R., “Multifocal motor neuropathy: Serum IgM anti-GM1 ganglioside antibodies in most patients detected using covalent linkage of GM1 to ELISA plates,”Neurology49:1289-1292 (1997).
Shibata, S. et al., “Autoantibodies to vascular heparan sulfate proteoglycan in systemic lupus erythematosus.,”Clin. Immunol. Immunopathol.70:114-123 (1994).
van den Berg, L.H. et al., “Anti-GM1 antibodies in patients with Guillain-Barre syndrome,”J. Neurol. Neurosurg. Psychiat55:8-11 (1992).
Simone, I.L. et al., “Serum and CSF anti-GM1 antibodies in patients with Guillain-Barre syndrome and Chronic Inflammatory Demyelinating Polyneuropathy,”J. Neurol. Sci.114:49-55 (1993).
Burger, D. et al., “Anti-myelin-associated glycoprotein antibodies in patients with a monoclonal IgM gammopathy and polyneuropathy, and a simplified method for the preparation of glycolipid antigens,”J. Immunol. Methods140:31-36 (1991).
Pestronk, A. et al., “Polyneuropathy syndromes associated with serum antibodies to sulfatide and myelin-associated glycoprotein,”Neurology41:357-362 (1991).
Cruz, M. et al., “Antibodies to myelin-associated glycoprotein are found in cerebrospinal fluid in polyneuropathy associated with monoclonal serum IgM,”Arch. Neurol.48:66-70 (1991).
Connolly, A.M. et al., “High-titer selective serum anti-beta-tubulin antibodies in chronic inflammatory demyelinating polyneuropathy,”Neurology43:557-562 (1993).
Fillit, H. and Lahita, R., “Antibodies to vascular heparan sulfate proteoglycan in patients with systemic lupus erythematosus,”Autoimmunity9:159-164 (1991).
Ilyas, A.A., et al., “Antibodies to acidic glycolipids in Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy,”J. Neurol. Sci.107:111-121 (1992).

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