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1.
Eur J Neurol ; 14(6): 617-20, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17539937

ABSTRACT

Myasthenia gravis (MG) is an autoimmune disease caused in 85% of the patients by acetylcholine receptor (AChR) antibodies. Non-AChR muscle antibodies, against titin and ryanodine receptor (RyR) are mainly found in sera of patients with thymoma or late-onset MG. The occurrence of RyR antibodies increases the risk for severe MG and should lead to active immunomodulating treatment already at MG onset. The aim in this study was to describe the association between symptoms at MG onset and antibody profile in 152 patients. Patients with RyR antibodies had the highest rate of bulbar, respiratory and neck involvement at MG onset. They also had the highest frequency of non-limb MG symptoms. Neck weakness occurred in 40%. Respiratory difficulties at MG onset occurred in patients with titin antibodies, with and without RyR antibodies. Patients with RyR antibodies have a distinctive non-limb MG symptom profile, with bulbar, ocular, neck, and respiratory symptoms. These features, identified as early as at the first examination by a neurologist, characterize the RyR antibody positive subgroup at MG onset.


Subject(s)
Antibodies/metabolism , Myasthenia Gravis/immunology , Myasthenia Gravis/metabolism , Ryanodine Receptor Calcium Release Channel/immunology , Adult , Aged , Chi-Square Distribution , Disability Evaluation , Female , Humans , Male , Middle Aged , Myasthenia Gravis/diagnosis , Myasthenia Gravis/surgery , Retrospective Studies , Severity of Illness Index , Thymectomy/methods
2.
Eur J Neurol ; 14(1): 60-5, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17222115

ABSTRACT

Post-polio syndrome (PPS) is characterized by new muscle weakness, atrophy, fatigue and pain developing several years after the acute polio. Some studies suggest an ongoing inflammation in the spinal cord in these patients. From this perspective, intravenous immunoglobulin (IvIg) could be a therapeutic option. We performed a double-blinded randomized controlled pilot study with 20 patients to investigate the possible clinical effects of IvIg in PPS. Twenty patients were randomized to either IvIg 2 g/kg body weight or placebo. Primary endpoints were changes in pain, fatigue and muscle strength 3 months after treatment. Surrogate endpoints were changes in cerebrospinal fluid (CSF) cytokine levels. Secondary endpoints were pain, fatigue and isometric muscle strength after 6 months. Patients receiving IvIg reported a significant improvement in pain during the first 3 months, but no change was noted for subjective fatigue and muscle strength. CSF levels of tumour necrosis factor-alpha (TNF-alpha) were increased compared with patients with non-inflammatory neurological disorders. In conclusion, in this small pilot study no effect was seen with IvIg treatment on muscle strength and fatigue, however IvIg treated PPS patients reported significantly less pain 3 months after treatment. TNF-alpha was increased in the CSF from PPS patients. The results are promising, but not conclusive because of the low number of patients studied.


Subject(s)
Fatigue/drug therapy , Immunoglobulins, Intravenous/therapeutic use , Postpoliomyelitis Syndrome/drug therapy , Aged , Double-Blind Method , Fatigue/physiopathology , Female , Humans , Immunoglobulins, Intravenous/pharmacology , Male , Middle Aged , Muscle Strength/drug effects , Muscle Strength/physiology , Pain/drug therapy , Pain/physiopathology , Pilot Projects , Postpoliomyelitis Syndrome/physiopathology
3.
Acta Neurol Scand Suppl ; 183: 19-23, 2006.
Article in English | MEDLINE | ID: mdl-16637922

ABSTRACT

Some myasthenia gravis (MG) patients have antibodies against skeletal muscle antigens in addition to the acetylcholine receptor (AChR). Two major antigens for non-AchR antibodies in MG are the Ca(2+) release channel of the sarcoplasmic reticulum, the ryanodine receptor (RyR) and titin, a gigantic filamentous muscle protein essential for muscle structure, function and development. RyR and titin antibodies are found mainly in thymoma MG patients and in a few late-onset MG patients and correlate with a severe MG disease. The presence of titin antibodies, which bind to key regions near the A/I junction and in the central I-band, correlates with myopathy. The immunosuppressant (FK506), which enhances Ca(2+) release from the RyR, seems to have a symptomatic effect on MG patients with RyR antibodies. The RyR antibodies recognize a region near the N-terminus important for channel regulation and inhibit Ca(2+) release in vitro. However, evidence that antibodies against the intracellular antigens RyR and titin are pathogenic in vivo is still missing.


Subject(s)
Antibodies/physiology , Muscle Proteins/immunology , Myasthenia Gravis/immunology , Protein Kinases/immunology , Ryanodine Receptor Calcium Release Channel/immunology , Connectin , Humans , Myasthenia Gravis/diagnosis , Myasthenia Gravis/therapy , Severity of Illness Index
4.
Acta Neurol Scand Suppl ; 183: 24-5, 2006.
Article in English | MEDLINE | ID: mdl-16637923

ABSTRACT

OBJECTIVES: To examine myasthenia gravis (MG) severity and long-term prognosis in seronegative, seropositive, and thymoma MG. MATERIALS AND METHODS: Four series of patients were studied retrospectively. Severity and treatment were assessed each year, and muscle antibodies were assayed. RESULTS: Seropositive MG patients had a more severe course than seronegative MG patients. MG severity was higher in non-thymectomized compared to thymectomized early-onset MG patients. MG severity did not differ between thymectomized and non-thymectomized late-onset patients. There was no significant difference in MG severity between thymoma and non-thymoma MG patients. CONCLUSIONS: MG is more severe in seropositive MG patients. With proper treatment, especially early thymectomy, the long-term prognosis is good in seropositive MG patients. The present studies indicate a benefit of thymectomy in early-onset MG, but no dramatic benefit in late-onset MG. Similar MG severity and outcome was seen in thymoma and non-thymoma MG.


Subject(s)
Myasthenia Gravis/diagnosis , Antibodies/blood , Cohort Studies , Female , Humans , Male , Myasthenia Gravis/blood , Myasthenia Gravis/complications , Prognosis , Receptor Protein-Tyrosine Kinases/immunology , Receptors, Cholinergic/immunology , Retrospective Studies , Severity of Illness Index , Thymoma/blood , Thymoma/complications , Thymoma/diagnosis , Thymus Neoplasms/blood , Thymus Neoplasms/complications , Thymus Neoplasms/diagnosis
6.
Acta Neurol Scand ; 112(1): 42-7, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15932355

ABSTRACT

OBJECTIVES: To study the causes and the rehabilitation outcome of traumatic spinal cord injury (SCI) in patients older than 60 years at the time of injury. MATERIAL: Forty-four patients were included. METHODS: The American Spinal Injury Association Motor Impairment Scale on admission and at discharge and the Functional Independence Measure Motor subscale at discharge were calculated retrospectively according to the patient records. The causes of injury and treatment were obtained. The MRI-scans in patients with cervical injuries during the last 5 years were evaluated. RESULTS: Thirty-four patients (77%) were injured after falling from a height, 24 with cervical lesions. Thirty-five patients (80%) had incomplete lesions and they had the best outcome with regard to functional level. MR images of 15 patients with cervical lesions revealed preexisting cervical stenosis in 80%. CONCLUSIONS: A high proportion of the patients had a cervical spinal stenosis and incomplete SCI; most of them regained good function.


Subject(s)
Spinal Cord Injuries/epidemiology , Spinal Cord Injuries/rehabilitation , Spinal Cord/pathology , Age Factors , Aged , Cervical Vertebrae/injuries , Cervical Vertebrae/pathology , Comorbidity , Female , Hospitalization/statistics & numerical data , Humans , Intervertebral Disc Displacement/epidemiology , Intervertebral Disc Displacement/pathology , Joint Dislocations/epidemiology , Joint Dislocations/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Norway , Risk Factors , Spinal Cord/physiopathology , Spinal Cord Injuries/pathology , Spinal Fractures/epidemiology , Spinal Fractures/pathology , Spinal Stenosis/epidemiology , Spinal Stenosis/pathology , Treatment Outcome
7.
Eur J Neurol ; 12(6): 413-8, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15885043

ABSTRACT

Around 10-20% of myasthenia gravis (MG) patients do not have acetylcholine receptor (AChR) antibodies (seronegative), of whom some have antibodies to a membrane-linked muscle specific kinase (MuSK). To examine MG severity and long-term prognosis in seronegative MG compared with seropositive MG, and to look specifically at anti-AChR antibody negative and anti-MuSK antibody negative patients. Seventeen consecutive seronegative non-thymomatous MG patients and 34 age and sex matched contemporary seropositive non-thymomatous MG controls were included in a retrospective follow-up study for a total period of 40 years. Clinical criteria were assessed each year, and muscle antibodies were assayed. There was no difference in MG severity between seronegative and seropositive MG. However, when thymectomized patients were excluded from the study at the year of thymectomy, seropositive MG patients had more severe course than seronegative (P < 0.001). One seropositive patient died from MG related respiratory insufficiency. The need for thymectomy in seronegative MG was lower than in seropositive MG. None of the seronegative patients had MuSK antibodies. This study shows that the presence of AChR antibodies in MG patients correlates with a more severe MG. With proper treatment, especially early thymectomy for seropositive MG, the outcome and long-term prognosis is good in patients with and without AChR antibodies.


Subject(s)
Antibodies/metabolism , Myasthenia Gravis/immunology , Receptor Protein-Tyrosine Kinases/immunology , Receptors, Cholinergic/immunology , Azathioprine/therapeutic use , Case-Control Studies , Female , Humans , Immunosuppressive Agents/therapeutic use , Incidence , Longitudinal Studies , Male , Myasthenia Gravis/diagnosis , Myasthenia Gravis/physiopathology , Myasthenia Gravis/surgery , Prognosis , Radioimmunoassay/methods , Retrospective Studies , Severity of Illness Index , Thymectomy/methods , Time Factors
8.
Acta Neurol Scand ; 111(2): 134-41, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15644074

ABSTRACT

We give an update on clinical, immunological, and therapeutic advances in the field of myasthenia gravis, including a summary of suggested therapeutic recommendations.


Subject(s)
Myasthenia Gravis , Cholinesterase Inhibitors/therapeutic use , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunosuppressive Agents/therapeutic use , Myasthenia Gravis/complications , Myasthenia Gravis/immunology , Myasthenia Gravis/therapy , Plasmapheresis , Thymectomy
10.
Eur J Neurol ; 10(6): 701-6, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14641516

ABSTRACT

Thymomas occurring in myasthenia gravis (MG) are usually of the cortical subtype and are usually treated by thymectomy. However, the factors that influence MG outcome in thymoma MG patients are not known. In a long-term study, MG severity and treatment was observed in 24 thymoma and 24 non-thymoma MG patients for up to 30 years, and the occurrence of muscle autoantibodies was assayed. The rate of complete stable remission was low and did not differ between the two groups. There was no significant difference in MG severity between thymoma and non-thymoma MG patients at any time during the study. Titin and ryanodine receptor (RyR) antibody occurrence was significantly higher in thymoma MG patients. Four thymoma (all titin and RyR antibody positive) and two non-thymoma (both titin and one RyR antibody positive) MG patients died from MG-related respiratory insufficiency. Seventy percent of thymoma and 75% of non-thymoma MG patients were treated with immunosuppressive drugs. The number of patients who received plasmapheresis did not differ in those who were treated because of acute MG deterioration, irrespective of planned surgery.This study shows equal MG severity and outcome in thymoma and non-thymoma MG, but the presence of RyR antibodies in thymoma MG and titin/RyR in non-thymoma MG indicates a less favorable prognosis.


Subject(s)
Myasthenia Gravis/complications , Thymoma/etiology , Thymus Neoplasms/etiology , Adrenal Cortex Hormones/therapeutic use , Adult , Age of Onset , Autoantibodies/immunology , Azathioprine/therapeutic use , Combined Modality Therapy , Connectin , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Muscle Proteins/immunology , Myasthenia Gravis/mortality , Myasthenia Gravis/surgery , Protein Kinases/immunology , Receptors, Cholinergic/immunology , Ryanodine Receptor Calcium Release Channel/immunology , Thymectomy , Thymoma/mortality , Thymoma/surgery , Thymus Gland/pathology , Thymus Neoplasms/mortality , Thymus Neoplasms/surgery , Treatment Outcome
11.
J Neuroimmunol ; 139(1-2): 141-4, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12799031

ABSTRACT

We studied the relationship between post-polio syndrome (PPS) and GM1 antibodies, since such antibodies have been associated with PPS and motor neuron disorders. Sera from 144 patients with previous poliomyelitis (105 paralytic, 22 nonparalytic and 17 PPS), 60 with previous Guillain-Barré syndrome, 44 with amyotrophic lateral sclerosis (ALS) and 22 healthy blood donors were analyzed with ELISA for GM1 IgM, IgG and IgA antibodies. GM1 antibodies were present in 14% of the PPS patients, but the prevalence did not differ significantly from that of the other groups. Our study does not support the hypothesis that GM1 antibodies are involved in the pathogenesis of PPS.


Subject(s)
Autoantibodies/blood , Autoantibodies/immunology , G(M1) Ganglioside/immunology , Poliomyelitis/complications , Poliomyelitis/immunology , Postpoliomyelitis Syndrome/immunology , Adult , Aged , Aged, 80 and over , Amyotrophic Lateral Sclerosis/blood , Amyotrophic Lateral Sclerosis/immunology , Guillain-Barre Syndrome/blood , Guillain-Barre Syndrome/immunology , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Male , Middle Aged , Motor Neurons/immunology , Motor Neurons/pathology , Peripheral Nerves/immunology , Peripheral Nerves/pathology , Peripheral Nerves/physiopathology , Poliomyelitis/blood , Postpoliomyelitis Syndrome/blood , Postpoliomyelitis Syndrome/physiopathology
12.
Eur Neurol ; 49(4): 210-7, 2003.
Article in English | MEDLINE | ID: mdl-12736536

ABSTRACT

OBJECTIVE: To study the clinical effect of thymectomy in a well-defined early-onset MG subgroup and to correlate it to MG severity, the presence of circulating muscle autoantibodies, and the need for pharmacological treatment in a long-term setting. METHODS: Fifty-two consecutive AChR antibody-positive early-onset MG patients (34 thymectomized and 18 nonthymectomized) were included. Severity was assessed and the pharmacological treatment monitored on a yearly basis, starting from the year of MG onset, for 5, 10, 15, and 20 consecutive years; AChR, titin, and RyR antibodies were assayed. RESULTS: In the four follow-up groups, MG severity was significantly higher in nonthymectomized compared to thymectomized MG patients. The postthymectomy MG improvement was significant and persistent. There were 21/34 remissions in thymectomized patients and only 4/18 in the nonthymectomized group. Patients with initially high or low AChR antibody concentration had a similar thymectomy outcome. Only 6 patients had titin antibodies, and none had RyR antibodies. CONCLUSION: The present study indicates a benefit of thymectomy in early-onset MG. The muscle autoantibody concentration does not influence the outcome of thymectomy in early-onset MG.


Subject(s)
Autoantibodies/blood , Muscle Weakness/physiopathology , Myasthenia Gravis/therapy , Thymectomy , Acetylcholine/blood , Acetylcholine/immunology , Adrenal Cortex Hormones/therapeutic use , Adult , Age of Onset , Cholinesterase Inhibitors/therapeutic use , Connectin , Female , Follow-Up Studies , Humans , Male , Muscle Proteins/blood , Muscle Proteins/immunology , Muscle Weakness/etiology , Muscles/immunology , Myasthenia Gravis/blood , Plasmapheresis , Protein Kinases/blood , Protein Kinases/immunology , Pyridostigmine Bromide/therapeutic use , Remission Induction , Retrospective Studies , Ryanodine Receptor Calcium Release Channel/blood , Ryanodine Receptor Calcium Release Channel/immunology , Severity of Illness Index , Thymus Gland/pathology , Thymus Gland/surgery , Treatment Outcome
13.
J Epidemiol Community Health ; 57(5): 368-72, 2003 May.
Article in English | MEDLINE | ID: mdl-12700222

ABSTRACT

OBJECTIVE: To examine and compare the long term outcome after polio in an east European and a west European country with different access to rehabilitation and with different medical and social conditions. DESIGN AND SETTING: The patients who were acutely hospitalised for polio 1950-54 in the University Hospital in Bergen, Norway and 1958 in the University Hospital in Tartu, Estonia received the mailed questionnaire in the period between January 1998 and December 1998. PATIENTS: Patient files concerning 334 patients hospitalised in Tartu and 243 patients hospitalised in Bergen were obtained; of these 128 Estonian and 148 Norwegian patients were re-examined. MAIN RESULTS: Despite more pronounced disability in the acute stage, significantly more Norwegian patients were working full time and part time in 1998 (p<0.0001) and also through the period 1958-1998. In both countries, 30% of patients had manual work and 18% changed profession during their career. Low income (below 50% of national average) was reported by 73% of Estonian and 35% of Norwegian patients (p<0.0001). Except for the odds ratio for muscular pain of 1.89 (95%CI =1.14 to 3.14) for Norwegian patients, new symptoms indicating late progression did not differ. Norwegian patients were more independent with significantly less need for assistance in housekeeping (p=0.02), whereas the use of orthopaedic devices did not differ. CONCLUSIONS: The long term outcome after polio is different in eastern and western Europe. Access to continuous rehabilitation seems to maintain physical independence in polio patients, improves their ability to earn their own income, and lessens the need for disability pensions.


Subject(s)
Poliomyelitis/rehabilitation , Activities of Daily Living , Disability Evaluation , Employment , Estonia/epidemiology , Exercise , Female , Health Services Accessibility , Humans , Income , Long-Term Care , Male , Middle Aged , Norway/epidemiology , Poliomyelitis/epidemiology , Postpoliomyelitis Syndrome/etiology , Surveys and Questionnaires , Treatment Outcome
15.
Eur J Neurol ; 9(1): 55-61, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11784377

ABSTRACT

Thymectomy is still widely carried out in myasthenia gravis (MG) patients, but its role, especially in late-onset MG patients, is not established. These patients are immunologically heterogeneous, some with thymoma-like and others with early onset-like features. We evaluated whether any therapeutic effects of thymectomy correlate with the presence of non-acetylcholine receptor (AChR) muscle antibodies. The severity of MG, and titin and ryanodine receptor (RyR) antibodies, were assessed yearly starting from MG onset in 21 thymectomized and 22 non-thymectomized AChR antibody positive late-onset MG patients, who were followed for 2, 3 and 5 years. Clinical or pharmacological remission were seen in six of 11 titin antibody negative but none of the 10 titin antibody positive thymectomized patients, however, the non-thymectomized cases showed an opposite trend. The three MG-related deaths were all in patients with titin antibodies. There was no significant difference in MG severity between thymectomized and non-thymectomized patients; 2 years after MG onset, both groups were significantly improved. This study showed no dramatic benefit from thymectomy in late-onset MG in general. Any limited improvement appeared less likely in cases with titin and/or RyR antibodies.


Subject(s)
Autoantibodies/immunology , Muscle, Skeletal/immunology , Myasthenia Gravis/immunology , Myasthenia Gravis/therapy , Thymectomy , Age of Onset , Aged , Atrophy , Cohort Studies , Connectin , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Muscle Proteins/immunology , Muscle Weakness/etiology , Muscle Weakness/physiopathology , Myasthenia Gravis/pathology , Protein Kinases/immunology , Receptors, Cholinergic/immunology , Ryanodine Receptor Calcium Release Channel/immunology , Thymus Gland/pathology
16.
J Neurol ; 248(6): 500-5, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11499641

ABSTRACT

243 patients were diagnosed with acute poliomyelitis (polio) in Western Norway between 1950 and 1954; 186 were paralytic and 57 non-paralytic. This study examines how polio influenced their education, employment, profession, annual income, marital status and energy for leisure activities. 149 of the patients identified were alive and 98 of the matched controls responded to a questionnaire. Education length did not differ between acute paralytic polio patients, acute non-paralytic polio patients and controls. Fifty percent of the patients with residual weakness and 77 % of the patients with normal muscle power were employed, against 73 % of the controls (P=0.014). A higher proportion of patients without motor deficits had manual work than those with weakness or controls (P=0.002). There was no significant association between severity of weakness and education, employment and profession. Physical ability had been an important factor for the choice of education and profession for all the polio patients, but not for controls (P < 0.001). Annual income did not differ significantly between patients and controls. Residual weakness increased the chance of being single (P=0.023), although as many as 79% had married. 53 % of the patients with weakness claimed that fatigue prevented hobbies, compared wich 31% of the other patients and only 16% of the controls (P < 0.001). There was no significant association between severity of weakness and fatigue. In conclusion, the polio patients are generally well educated, provide their own income and marry. However, their polio has influenced choice of education and profession, and polio patients with persisting weakness differ from controls and polio patients without motor deficits regarding employment and marital status.


Subject(s)
Disabled Persons , Education , Employment , Poliomyelitis , Quality of Life , Aged , Fatigue , Female , Follow-Up Studies , Humans , Income , Male , Middle Aged , Muscle Weakness , Recreation
17.
Tidsskr Nor Laegeforen ; 121(15): 1817-20, 2001 Jun 10.
Article in Norwegian | MEDLINE | ID: mdl-11464688

ABSTRACT

BACKGROUND: Acute myelitis is a clinical condition affecting the motor, sensor or autonomic function of the spinal cord. The etiology is often unknown, although a diversity of pathogens have been associated with acute myelitis. MATERIALS AND METHODS: Based on relevant literature we present an overview of the most important pathogens responsible for infectious acute myelitis in northern Europe, as well as recommendations regarding diagnostic guidelines. RESULTS: The pathogenic mechanisms are only partly known. Both replication of the pathogen, cellular defence mechanisms after invasion of the central nervous system, and the immune system seem to be important for the neurological damage. INTERPRETATION: Identification of a causative agent is important for the etiologic diagnosis and offers the possibility of specific treatment.


Subject(s)
Myelitis/microbiology , Acute Disease , Europe , Humans , Microbiological Techniques , Myelitis/diagnosis , Myelitis/drug therapy , Myelitis/virology , Practice Guidelines as Topic
18.
Acta Physiol Scand ; 171(3): 379-84, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11412151

ABSTRACT

Some myasthenia gravis (MG) patients have antibodies against skeletal muscle antigens in addition to the acetylcholine receptor (AChR). A major antigen for these antibodies is the Ca2+ release channel of the sarcoplasmic reticulum the ryanodine receptor (RyR). These antibodies are found mainly in MG patients with a thymoma MG and correlate with severe MG symptoms. The antibodies recognize a region near the N-terminus on the RyR, which seems to be of importance for RyR regulation. The antibodies cause allosteric inhibition of RyR function in vitro, inhibiting Ca2+ release from sarcoplasmic reticulum.


Subject(s)
Autoimmunity , Myasthenia Gravis/immunology , Ryanodine Receptor Calcium Release Channel/immunology , Animals , Humans , Immunosuppressive Agents/therapeutic use , In Vitro Techniques , Myasthenia Gravis/complications , Myasthenia Gravis/drug therapy , Thymoma/complications , Thymoma/immunology , Thymus Neoplasms/complications , Thymus Neoplasms/immunology
20.
Vet Immunol Immunopathol ; 78(1): 97-105, 2001 Jan 10.
Article in English | MEDLINE | ID: mdl-11182151

ABSTRACT

Similar to human autoimmune myasthenia gravis (MG), canine MG occurs spontaneously and is associated with autoantibodies against the nicotinic acetylcholine receptor (AChR). In addition to AChR, human MG patients with thymoma or late-onset MG have antibodies against titin and ryanodine receptor (RyR). The objective of this study was to establish if dogs with confirmed MG (AChR antibody titer >0.6 nmol/l) also developed titin and RyR antibodies and identify possible associations with thymoma, late age of onset, or severity of clinical signs. Sera from dogs (n=430) with previously diagnosed autoimmune MG (N=415), other immune-mediated neuromuscular disorders including polymyositis (PM) and masticatory muscle myositis (N=5), and control dogs (N=10) were evaluated for the presence of titin antibodies in ELISA using MGT-30 as antigen, a peptide representing the main immunogenic region (MIR) for human titin antibodies. Titin antibody positive sera were further examined for RyR antibodies in Western blots using a RyR fusion protein (pc2-RyR) as antigen, which covers the MIR for human MG sera. Titin antibodies were found in sera of 80/430 dogs. Thymoma was present in 11/80 and age of onset was after 4 years in 66/80 titin positive dogs. Two of the titin positive dogs had PM. RyR antibodies were found in 13/80 sera (8/13 thymoma, 12/13 age of onset after 4 years, and 1/13 PM). Neither titin nor RyR antibodies were found in sera of healthy control dogs. Acute fulminating MG was described in five dogs with both titin and RyR antibodies. From these studies we conclude that titin and RyR antibodies in canine and human MG have a similar association with thymoma, late-onset MG, and possibly with more severe forms of MG.


Subject(s)
Autoantibodies/blood , Dog Diseases/immunology , Muscle Proteins/immunology , Myasthenia Gravis/veterinary , Protein Kinases/immunology , Ryanodine Receptor Calcium Release Channel/immunology , Thymoma/immunology , Thymoma/veterinary , Thymus Neoplasms/veterinary , Age of Onset , Animals , Autoantibodies/immunology , Blotting, Western/veterinary , Connectin , Dogs , Immunoglobulin G/blood , Immunoglobulin G/immunology , Myasthenia Gravis/immunology , Radioimmunoassay/veterinary , Thymus Neoplasms/immunology
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