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Efeito da administração do G-CSF nos mecanismos efetores e imunorreguladores na neurite experimental autoimune induzida em ratos Lewis = Effect of the administration of the G-CSF onto the effector and immuneregulatory mechanisms of the experimental autoimmune neuritis induced in Lewis rats / Effect of the administration of the G-CSF onto the effector and immuneregulatory mechanisms of the experimental autoimmune neuritis induced in Lewis ratsPradella, Fernando, 1987- 03 November 2013 (has links)
Orientadores: Alessandro dos Santos Farias, Leonilda Maria Barbosa dos Santos / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-23T01:58:27Z (GMT). No. of bitstreams: 1
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Previous issue date: 2013 / Resumo: O resumo poderá ser visualizado no texto completo da tese digital / Abstract: The abstract is available with the full electronic document / Mestrado / Imunologia / Mestre em Genética e Biologia Molecular
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Grados de fuerza muscular y su relación con los subtipos del síndrome de guillain barré en los pacientes afectados entre los años 2009 al 2013Bellodas Ramos, Karla Geraldine January 2015 (has links)
OBJETIVOS: Determinar los grados de fuerza muscular y la relación que tienen con los subtipos del síndrome de Guillain Barré en los pacientes afectados desde el año 2009 al 2013 del Instituto Nacional de Ciencias Neurológicas.
MATERIALES Y MÉTODOS: Estudio de tipo descriptivo, correlacional, retroprospectivo, transversal; se estudio a 31 pacientes que fueron afectados con el Síndrome del Guillain Barré entre los años 2009 al 2013 del Instituto Nacional de Ciencias Neurológicas entre los 20 a los 79 años de edad; se utilizó como instrumentos el test manual de exploración muscular o test de fuerza muscular manual y se relacionó la variable con el subtipo del Síndrome de Guillain Barré extraída de los datos de la historia clínica de los pacientes.
RESULTADOS: Los resultados del cruce de las variables subtipo de Síndrome de Guillain Barré y los grados de Fuerza muscular (divididas en dos grupos: con alteración funcional o sin alteración funcional) por medio de tablas de contingencia con la utilización de las pruebas de Chi –cuadrado el grado de los significancia de p > 0,05, con lo cual no se p grados de Fuerza Muscular no podrán ser probadas. Se observaron que las alteraciones de los grados de fuerza muscular a nivel funcional están presenten a predominio de los grupos musculares de los segmentos distales, tanto de miembros superiores como miembros inferiores.
CONCLUSIONES: No se pudo demostrar la relación entre los subtipos del Síndrome de Guillain Barré, las posibles causas de los resultados aún se mantienen en discusión para futuras investigaciones. Las alteraciones de los grados de fuerza muscular funcional son predominantes en los segmentos distales. / OBJECTIVES: To determine the degree of muscle strength and the relationship they have with the subtypes of Guillain Barre syndrome in patients affected from 2009 to 2013 of the Instituto Nacional de Ciencias Neurológicas.
MATERIALS AND METHODS: Descriptive, correlational, retroprospective, transversal; 31 patients who were affected with Guillain Barre Syndrome from 2009 to 2013 of the Instituto Nacional de Ciencias Neurológicas, the age range is 20 to 79 years old; Manual muscle test was used as instruments and it was related with the subtype of Guillain Barré syndrome, that data was extracted from medical records of patients.
RESULTS: The results from the intersection of variables subtype of Guillain Barré and degrees of muscular strength (divided into two groups: those with functional impairment or without functional impairment ) using contingency tables and using Chi -square test the significance level of p> 0.05 , I was not found a significant difference between between subtypes of Guillain Barre syndrome and degrees of muscle strength. It was found degrees of muscle strenght alteration at the functional level a of the distal muscle groups in the upper limbs and lower limbs.
CONCLUSIONS: it was not found a significant correlation between between subtypes of Guillain Barré and degrees of muscle strength. The possible causes of the results still are found under discussion for future studies. Alterations in the levels of functional muscle strength are predominant in the distal segments.
KEYBOARDS: Subtype Guillain Barre Syndrome, Muscular Strength, degree of functional muscle strength, muscle strength degree of functional impairment.
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Infektionen durch Mycoplasma pneumoniae in Franken in den Jahren 2000-2003 : Untersuchungen eines Ausbruches in Ebrach sowie stationärer Patienten der Universitätskinderklinik Würzburg / Infections due to Mycoplasma pneumoniae between 2000-2003 in Franken, Bavaria, GermanySchmitz, Sabine January 2010 (has links) (PDF)
Die Studie diente der retrospektiven Untersuchung des Ausbruches von Mp-Infektionen in Ebrach, Franken, der von Oktober des Jahres 2000 bis Februar 2001 andauerte. Ziel war es, die epidemiologischen Charakteristika, also Informationen zu Verteilung und Ausbreitungsweisen der Erkrankung, aber auch zu Symptomen und Befunden, Manifestationsformen und Komplikationen, Therapie und Diagnostik zu erhalten. Darüber hinaus sollten Erkenntnisse zu Patienten mit Mykoplasmeninfektionen, die in den Jahren 2000 bis 2003 in der Universitätskinderklinik Würzburg behandelt wurden, gewonnen und mit Daten der Patienten aus Ebrach verglichen werden. In Ebrach bestand bei 177 Patienten der Verdacht einer akuten Mykoplasmeninfektion. Ausgehend von einer dritten Grundschulklasse, die einige Tage geschlossen werden musste, da innerhalb von 16 Tagen 9 Schüler an einer Pneumonie und 3 Schüler an einer Bronchitis erkrankt waren, hatte sich die Infektion auf insgesamt 78 Personen, vor allem Familienmitglieder, aber auch Nachbarn und Freunde der betroffenen Schüler ausgebreitet. Die meisten Patienten klagten über Husten und Fieber. In erster Linie traten Entzündungen des unteren Respirationstraktes (50% Bronchitiden, 38,5% Pneumonien) auf. Bei 9 Patienten wurde ein Exanthem beobachtet. Eine Patientin musste wegen eines Guillain-Barré-Syndroms in der neurologischen Abteilung der Universitätsklinik Würzburg behandelt werden. In den Jahren 2000 bis 2003 bestand bei 125 Patienten der Universitätskinderklinik Würzburg der Verdacht auf Vorliegen einer Mp-Infektion. Bestätigt wurde dieser in 43 Fällen. Die Patienten waren zwischen 3 und 16 Jahre alt. Insgesamt waren etwas mehr Jungen betroffen, Komplikationen traten deutlich häufiger bei Mädchen auf. Die Patienten, die einer stationären Behandlung bedurften, wiesen schwerere Erkrankungsverläufe oder seltenere Manifestationsformen auf (65% Pneumonien, 34% Komplikationen). So wurden unter anderem 6 Patienten mit Mykoplasmen-assoziierter Fazialisparese, 4 Patienten mit Meningitis und jeweils ein Patient mit Enzephalitis, Trochlearisparese, Vestibularisausfall, Hörverlust, Perimyokarditis und Uveitis anterior und nephrotischem Syndrom beobachtet. Pathognomonische Befunde konnten weder unter den Ebracher Patienten noch in der Kinderklinik ausgemacht werden. Vielmehr spricht die Konstellation bestimmter Symptome und Untersuchungsergebnisse wie Husten, Fieber, relativ guter Allgemeinzustand bei radiologischem Pneumonienachweis oder Differenz der Blutsenkungsreaktion bei Raumtemperatur und 4°C für das Vorliegen einer Mykoplasmeninfektion. Eine deutliche Erhöhung der Inzidenz von Mykoplasmeninfektionen in der Kinderklinik im Zeitraum des Ausbruches von Ebrach war nicht zu verzeichnen. Dass Schüler als Überträger der Infektion in Familien und unter Spielkameraden fungieren, war bekannt, die Ausbreitung der Erkrankung innerhalb des Klassenzimmers ist jedoch selten in diesem Ausmaß beobachtet worden und verdient weitere Untersuchungen. Festzuhalten bleibt also, dass bei der Diagnose einer Mykoplasmeninfektion mittels serologischer Methoden mit einer verzögerten Immunantwort zu rechnen ist und deshalb häufig ein Direktnachweis der Erreger mittels PCR notwendig wird. Darüber hinaus ist die Bestimmung der Blutkörperchensenkungsgeschwindigkeit bei Raum- und Kühlschranktemperatur ein einfaches Mittel, welches aber diagnostisch zusätzlich wichtige Hinweise auf eine Infektion mit Mycoplasma pneumoniae liefern kann. Im Gegensatz dazu erbringt die klinische Untersuchung häufig keine aussagekräftigen, diagnostisch weiterführenden Ergebnisse. Wichtig bezüglich der Therapie ist die frühzeitige und ausreichend lange (10 bis 14 Tage) Gabe von gegen Mykoplasmen wirksamen Antibiotika wie vor allem Makrolid-Antibiotika. / This is a retrospective study of an outbreak of Mycoplasma pneumoniae infections between october 2000 and february 2001 in Ebrach, Franken, Germany. We wanted to get information about epidemiologic characteristics, such as spread of infection, clinical manifestations and complications, as well as influence of therapy, and possibilities of diagnostics. Furthermore we monitored patients with Mycoplasma pneumoniae infections which led to hospitalisation in the pediatric department of Würzburg university hospital and compared them to the patients in Ebrach. In Ebrach a total of 177 patients were thought to have an MP infection. It started in year 3 of primary school, where within 16 days 9 pupils suffered from pneumonia due to MP and 3 children had MP bronchitis. For this reason the pupils where not allowed to attend school for a few days. Beginning with the school children the infection reached 78 persons, mainly parents of the children but also neighbours and friends for example from the football team. Most of them suffered from coughs and fever. Manifestations were infections of the lower respiratory tract (38,5% pneumonia, 50% bronchitis), 9 patients suffered from cutaneous symptoms (exanthema). One patient had to be hospitalized because of a Guillain-Barre-syndrom. Between 2000 and 2003, 125 patients of the pediatric department of the Würzburg university hospital were thought to have MP infections. In 43 cases the MP infection was diagnosed. Patients were between 3 and 16 years old, there were bit more cases amongst males but females got more complications. Hospitalized patients showed more severe manifestatons (65% pneumonia) or complications (34%). These were for example 6 children with Bells palsy, 4 children with menigitis and one of each of the following manifestations: encephalitis, cranial nerve palsy of trochlearis and vestibularis, hearing loss, permyocarditis, uveitis anterior, nephrotic syndrom. No special symptoms which could be said to be pathognomonic were found in either Ebrach or amongst the hospitalized patients. The special constellation of pathological findings much rather suggests a diagnosis of an MP infection: cough, fever, quite good clinical condition, radiographic evidence of pneumonia, different wsg results at 37°C and 4°C. The incidence of MP infections among hospitalized patients did not increase during the time of the outbreak in Ebrach. It is already known that pupils are possible vectors but such a spread of MP infection in the classroom has seldom been observed before and needs further investigation. Serologic diagnosis needs more time because of the delayed immune response of the host and this is why pcr is often necessary. Antibiotic treatment with effective drugs such as macrolides should be taken into consideration early and administered for a long enough period.
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Generation and analysis of transgenic mice expressing ovalbumin as a neo-self antigen under control of the myelin basic protein promoter / Generation and analysis of transgenic mice expressing ovalbumin as a neo-self antigen under control of the myelin basic protein promoterToben, Catherine Gisela January 2005 (has links) (PDF)
In this project two novel murine autoimmune models were to be established in an attempt to further investigate the nervous system disorders of Multiple Sclerosis and Guillain Barré Syndrome. Previous experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune neuritis (EAN) models have demonstrated that T cells play a major role in these diseases. Which roles CD4 and CD8 T cells specifically have in the initiation, propagation and termination of an autoimmune nervous system disorder remains controversial. To this end two transgenic mice specifically expressing the neo-antigen (Ag) ovalbumin (OVA) in either the central nervous system (CNS) or peripheral nervous system (PNS) were to be generated. The myelin basic protein (MBP) is a major component of the myelin sheath both within the CNS and the PNS. Therefore the MBP promoter was employed for its distinct regulatory elements to facilitate exclusive CNS or PNS OVA expression. The adoptive transfer of OVA specific MHCI restricted (OT-I) and MHCII restricted (OT-II) TCR Tg T cells extended the OVA Tg mouse model by allowing potentially encephalitogenic T cells to be tracked in vivo. Specificity for the target Ag should enable the dynamic role of antigen specific T cells in neuroinflammatory diseases to be revealed in more detail. / Im Rahmen der vorliegenden Arbeit wurden zwei neue Mausmodelle für Autoimmunerkrankungen etabliert, um weitere Fortschritte bei der Aufklärung der zellulären und molekularen Interaktionen bei den Erkrankungen des Nervensystems Multiple Sklerose und Guillain Barré Syndrom zu erzielen. In früheren Experimenten mit EAE (experimentelle autoimmune Enzephalomyelitis) und EAN (experimentelle autoimmune Neuritis) konnte bereits gezeigt werden, dass T-Zellen eine Hauptrolle bei diesen Erkrankungen spielen, wobei jedoch die Bedeutung von CD4 bzw. CD8 T-Zellen im Einzelnen noch nicht aufgeklärt ist. Zu diesem Zwecke sollten zwei transgene (Tg) Mauslinien generiert werden, die speziell entweder im peripheren (PNS) oder im zentralen (ZNS) Nervensystem das Zielantigen OVA exprimieren. MBP ist eine Hauptkomponente der Myelinscheide sowohl im ZNS als auch im PNS. Daher kam der Myelin Basic Protein (MBP) Promoter zum Einsatz, dessen unterschiedliche regulatorischen Elemente eine Expression von intaktem OVA ausschließlich im ZNS bzw. ausschließlich im PNS steuern können. Eine Erweiterung dieser OVA tg Mausmodelle stellte der adoptive Transfer von OVA spezifischen MHCI-restringierten OTI und MHCII-restringierten OTII T-Zellen dar, da es so möglich wurde, potentiell enzephalitogene T-Zellen in vivo zu verfolgen. Dadurch sollte ebenfalls eine detailliertere Darstellung der dynamischen Rolle von antigenspezifischen T-Zellen bei neuroinflammatorischen Erkrankungen ermöglicht werden.
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Generation and analysis of transgenic mice expressing ovalbumin as a neo-self antigen under control of the myelin basic protein promoterToben, Catherine Gisela. Unknown Date (has links) (PDF)
University, Diss., 2005--Würzburg. / Erscheinungsjahr an der Haupttitelstelle: 2005.
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S?ndrome de Guillain-Barr?: epidemiologia, progn?stico e fatores de riscoDourado J?nior, M?rio Em?lio Teixeira 17 March 2015 (has links)
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Previous issue date: 2015-03-17 / Indrodu??o. A S?ndrome de Guillain-Barr? (SGB) ? uma polineuropatia imunomediada,
sendo, atualmente, a mais frequente causa de paralisia aguda
neuromuscular. As principais variantes dessa s?ndrome s?o: a polineuropatia
desmielinizante inflamat?ria aguda (PDIA), a neuropatia axonal motora aguda
(NAMA), a neuropatia axonal motora e sensitiva aguda (NAMSA), e a s?ndrome de
Miller-Fisher. H? tamb?m diferen?as na distribui??o geogr?fica destas variantes. A
resposta imune aberrante, p?s infec??o, parece ser resultante de um mimetismo
molecular, devido a forma??o de autoanticorpos e ativa??o do sistema
complemento e de citocinas. S?o encontrados polimorfismos bial?licos nos genes
codificadores dos receptores das fra??es Fc das imunoglobulinas (FcRIIa, FcRIIIa
e FcRIIIb) que afetam a afinidade e efici?ncia na resposta imune celular, sugerindo
a exist?ncia de susceptibilidade individual no risco de desenvolver a SGB. No
Brasil, h? poucos estudos epidemiol?gicos sobre a SGB e nenhum relato sobre a
frequ?ncia das variantes e suas manifesta??es cl?nicas. Os objetivos deste estudo
foram: (1) caracterizar a SGB e suas manifesta??es cl?nicas em uma coorte de
pacientes com SGB oriundos do Estado do Rio Grande do Norte (RN); (2)
determinar se polimorfismos em receptores FcR est?o envolvidos com o risco de
doen?a, e (3) avaliar a express?o g?nica global buscando identificar poss?veis vias
que poderiam ser moduladas na fase inicial da doen?a e, consequentemente,
diminuir o tempo de doen?a.
Metodologia. Foram recrutados 149 casos de SGB diagnosticados entre 1994-
2013 no RN, tendo sido avaliados os dados cl?nicos e laboratoriais visando a
determinar a evolu??o. DNA e RNA foram extra?dos do sangue perif?rico e
anticorpos antiganglios?deos foram determinados em amostras de soro. Foram
genotipados polimorfismos nos genes FCGR2A e FCGR3A, em pessoas com SGB
(n=141) e controles saud?veis (n=364), sendo ainda analisadas as express?es
g?nicas globais de 12 pacientes com SGB, por RNAseq. As amostras de sangue
para os estudos de express?o g?nica foram coletadas ao diagn?stico e p?srecupera??o.
Resultados. A incid?ncia de SGB foi de 0,3/100 mil pessoas no RN, sem presen?a
de sazonalidade, com os casos ocorrendo em uma idade mais jovem. A SGB foi precedida por infec??es em 63,7%, sendo a diarreia associada a variante axonal
(p=0,025). A PDIA foi a variante mais frequente (81,8%), seguida de NAMA
(14,7%) e de NAMSA (3,3%). A distribui??o da fraqueza muscular correlacionou
com as variantes, sendo a proximal mais frequente na PDIA, enquanto a distal
predominou na variante axonal. O nadir < 10 dias ocorreu em 84,6% dos indiv?duos
na variante axonal e 42,4% dos casos com PDIA (P<0,0001). A forma
desmielinizante apresentou uma recupera??o na deambula??o mais r?pida do que
a variante axonal (P<0,0001). A mortalidade de SGB foi de 5,3%. O pior
progn?stico aos 12 meses estava associado com a variante axonal (OR 17,063; P
= 0,03) e no tempo de melhora um ponto na escala funcional de Hughes (OR
1,028; P = 0.03). As distribui??es dos gen?tipos e alelos em FCGR2A (p=0,367) e
em FCGR3A (p=0,2430) n?o foram diferentes entre os pacientes com SGB e
controles. A an?lise da express?o g?nica global mostrou varia??o na express?o
dos mRNAs de isoformas de prote?nas associadas ? fase sintom?tica da doen?a.
Conclus?es. N?o h? sazonalidade na ocorr?ncia da SGB no RN, havendo um
predom?nio da variante desmielinizante e 50% dos casos tinham idade inferior a 20
anos. A variante axonal est? associada ao mau progn?stico. O diagn?stico precoce
e a identifica??o da variante, acompanhada de interven??es adequadas, levam a
diminui??o da morbidade a longo prazo. Varia??es polim?rficas nos genes de
FCGR parecem n?o influenciar a susceptibilidade ou o curso da SGB nessa
popula??o. Varia??es na express?o g?nica apontam para vias de desregula??o e
altera??es em intera??es transcricionais, que podem ser utilizadas como potenciais
alvos de modula??o. / Introduction. Guillain-Barr? syndrome (GBS) is an immune-mediated
polyneuropathy and the principal cause of acute neuromuscular paralysis. The most
prominent GBS subtypes are: acute inflammatory demyelinating polyneuropathy
(AIDP), acute motor axonal neuropathy (AMAN), acute motor-sensory axonal
neuropathy (AMSAN) and Fisher syndrome (FS). Differences in geographical
distribution of variants have been reported. In Brazil, there are few studies
describing the characteristics of GBS, but none on the frequency of GBS variants
and their clinical manifestations. Infection-induced aberrant immune response
resulting from molecular mimicry and formation of cross-reacting antibodies,
contribute to complement activation. Functional biallelic polymorphism in
immunoglobulin receptors that influence the affinity of IgG subclasses and the type
of immune response have been described, suggesting genetic susceptibility to
developing disease. It remains unclear whether individuals carrying different FCGR
alleles have differential risk for GBS and?or disease severity. The goals of this study
were: (1) To characterize GBS and describe the clinical findings in a cohort of
patients with GBS from the state of Rio Grande do Norte, Brazil; (2) to determine
whether polymorphism in FCGR were associated with development of GBS, and (3)
to tease out whether the global gene expression studies could be a tool to identify
pathways and transcriptional networks which could be regulated and decrease the
time of disease.
Methods. Clinical and laboratory data for 149 cases of GBS diagnosed from 1994
to 2013 were analyzed. Genomic DNA and total RNA were extracted from whole
blood. Antigangliosides antibodies were determined in the sera. In addition, we
also assessed whether FCGR polymorphism are present in GBS (n=141) and blood
donors (n=364), and global gene expressions were determined for 12 participants
with GBS. Blood samples were collected at the diagnosis and post-recovery.
Results. AIDP was the most frequent variant (81.8%) of GBS, followed by AMAN
(14.7%) and AMSAN (3.3%). The incidence of GBS was 0.3 ? 100,000 people for
the state of Rio Grande do Norte and cases occurred at a younger age. GBS was
preceded by infections, with the axonal variant associated with episodes of diarrhea
(P = 0.025). Proximal weakness was more frequent in AIDP, and distal weakness predominant in the axonal variant. Compared to 42.4% of cases with AIDP
(P<0.0001), 84.6% of cases with the axonal variant had nadir in <10 days.
Individuals with the axonal variant took longer to recover deambulation (P<0.0001).
The mortality of GBS was 5.3%. A worse outcome was related to an axonal variant
(OR17.063; P=0.03) and time required to improve one point in the Hughes
functional scale (OR 1.028; P=0.03). The FCGR genotypes and allele frequencies
did not differ significantly between the patients with GBS and the controls (FCGR2A
p=0.367 and FCGR3A p=0.2430). Global gene expression using RNAseq showed
variation in transcript coding for protein isoforms during acute phase of disease.
Conclusions. The annual incidence of GBS was 0.3 per 100,00 and there was no
seasonal pattern. A predominance of the AIDP variant was seen, and the incidence
of the disease decreased with age. The distribution of weakness is a function of the
clinical variants, and individuals with the axonal variant had a poorer prognosis.
Early diagnosis and variant identification leads to proper intervention decreasing in
long-term morbidity. FCGR polymorphisms do not seem to influence susceptibility to
GBS in this population. This study found deregulated genes and signs of
transcriptional network alterations during the acute and recovery phases in GBS.
Identification of pathways altered during disease might be target for immune
regulation and with potential to ameliorate symptoms.
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Detektion und Charakterisierung von Autoantikörpern gegen paranodale Proteine bei Patienten mit inflammatorischer Polyneuropathie / Detection and characterization of auto-antibodies against paranodal proteins in patients with inflammatory polyneuropathyAppeltshauser, Luise Theresia January 2018 (has links) (PDF)
Kürzlich wurden bei immunvermittelten Neuropathien Autoantikörper gegen Proteine
des paranodalen axoglialen Komplexes beschrieben. Deren Charakteristika,
Prävalenzen, pathophysiologische Relevanz sowie Bedeutung für Diagnostik
und Therapie sind jedoch noch nicht abschließend erforscht.
In dieser Studie wurden daher Seren und Plasmapheresematerial (PE-Material)
von 150 Patienten mit inflammatorischen Neuropathien, nämlich 105 mit chronisch
inflammatorischer demyelinisierender Polyneuropathie (CIDP), 21 mit Guillain-
Barré-Syndrom (GBS) und 24 mit multifokaler motorischer Neuropathie
(MMN), welche etablierte diagnostische Kriterien der jeweiligen Krankheit erfüllen,
sowie 74 Kontrollen mittels immunhistochemischen Färbungen an murinen
Zupfnervenpräparaten und/oder ELISA (Enzyme-linked Immunosorbent Assay)
auf Autoantikörper gegen die paranodalen Proteine Caspr, Contactin-1 und Neurofascin-
155 untersucht. Bei positivem Ergebnis wurde deren Spezifität mittels
immunhistochemischen Färbungen an transfizierten HEK (Human embryonic kidney)-
293-Zellen und Präinkubationsversuchen bestätigt. Es wurden die IgG-Subklassen
und die Antikörpertiter bestimmt und das Komplementbindungsverhalten
unter Zugabe von intravenösen Immunglobulinen (IVIG) mit zellbasierten und
ELISA-basierten Methoden analysiert. Klinische Merkmale und das Therapieansprechen
Antikörper-positiver Patienten wurden ermittelt und mit den experimentellen
Ergebnissen in Zusammenhang gesetzt.
IgG-Autoantikörper gegen Contactin-1 konnten bei vier Patienten mit CIDP nachgewiesen
werden, IgG-Autoantikörper gegen Caspr bei einem Patienten mit
CIDP und einer Patientin mit GBS. Es konnten keine weiteren Autoantikörper bei
CIDP-Patienten, GBS-Patienten, MMN-Patienten oder bei den Kontrollen detektiert
werden. Die Prävalenz von Autoantikörpern gegen axogliale paranodale Proteine
liegt somit in dieser Studie bei jeweils 4,76% bei CIDP und GBS und 0%
bei MMN. Die Antikörper gehörten bei Patienten in der akuten Erkrankungsphase
(zwei der CIDP-Patienten mit Anti-Contactin-1-Autoantikörpern und eine GBS-Patientin mit Anti-Caspr-Autoantikörpern) hauptsächlich den Subklassen IgG1
und IgG3 an, bei Patienten in der chronischen Phase (zwei der CIDP-Patienten
mit Anti-Contactin-1-Autoantikörpern, ein CIDP-Patient mit Anti-Caspr-Autoantikörpern)
überwog die Subklasse IgG4. Experimentell kam es zur Komplementbindung
und -aktivierung abhängig vom Gehalt der Subklassen IgG1-3, nicht
aber IgG4; diese konnte durch die Zugabe von IVIG dosisabhängig gemindert
werden. Alle Autoantikörper-positiven CIDP-Patienten zeigten einen GBS-artigen
Beginn mit einer schweren motorischen Beteiligung. Anti-Contactin-1-positive
Patienten kennzeichnete klinisch zusätzlich das Vorkommen einer Ataxie und eines
Tremors, Anti-Caspr-positive Patienten das Vorkommen starker neuropathischer
Schmerzen. Elektrophysiologisch standen neben Hinweisen auf eine Leitungsstörung
Zeichen einer axonalen Schädigung im Vordergrund. Als histopathologisches
Korrelat lagen eine nodale Architekturstörung und ein Axonverlust
vor. Die Patienten zeigten nur in der Anfangsphase der Erkrankung ein Ansprechen
auf IVIG. Bei drei CIDP-Patienten mit IgG4-Autoantikörpern (zwei Patienten
mit Anti-Contactin-1-Antikörpern und ein Patient mit Anti-Caspr-Antikörpern)
wurde eine Therapie mit Rituximab durchgeführt. Diese führte zu einer Titerreduktion
und zur zeitgleichen klinischen und elektrophysiologischen Befundbesserung
bei zwei Patienten.
Die in dieser Arbeit angewandten Screeningmethoden führten zum erfolgreichen
Nachweis von Autoantikörpern gegen paranodale axogliale Proteine. Die Patienten
mit positivem Autoantikörpernachweis definieren eine kleine Untergruppe mit
ähnlichen klinischen Merkmalen im Kollektiv der Patienten mit inflammatorischen
Polyneuropathien. Histopathologische Merkmale sowie das Therapieansprechen
auf antikörperdepletierende Therapie sprechen in Kombination mit den Ergebnissen
weiterer Studien zu paranodalen Autoantikörpern für eine pathogenetische
Relevanz der Autoantikörper. Mit einem charakteristischen, am Schnürring ansetzenden
Pathomechanismus könnten Neuropathien mit Nachweis von paranodalen
Autoantikörpern der kürzlich eingeführten Entität der Nodo-Paranodopathien
angehören. Die Komplementaktivierung und das Therapieansprechen der Patienten auf IVIG stehen möglicherweise in Zusammenhang mit der prädominanten
IgG-Subklasse. Diese könnte auch in Bezug auf die Chronifizierung eine
Rolle spielen. Der Nachweis von Autoantikörpern gegen paranodale Proteine hat
wohlmöglich in Zukunft direkte Konsequenzen auf das diagnostische und therapeutische
Prozedere bei Patienten mit CIDP und GBS; weitere klinische und experimentelle
Daten aus größeren, prospektiven Studien sind jedoch zum weiteren
Verständnis und zur Charakterisierung dieser Entität notwendig. / Autoantibodies against proteins of the paranodal axoglial complex have been described
in recent studies on immune-mediated neuropathies. Nevertheless, their
characteristics, prevalences, pathophysiological relevance and impact on diagnostics
and therapy have not been fully investigated.
Therefore, sera and plasmapheresis material (PE-material) of 150 patients with
inflammatory neuropathy, including 105 patients with chronic inflammatory demyelinating
polyneuropathy (CIDP), 21 patients with Guillain-Barré-Syndrome
(GBS) and 24 patients with multifocal motor neuropathy (MMN), fulfilling established
diagnostic criteria for the respective disease, as well as 74 controls were
screened for autoantibodies against the paranodal proteins caspr, contactin-1
and neurofascin-155 via immunohistochemic staining of murine teased fiber
preparations and/or ELISA (Enzyme-linked Immunosorbent Assay). In the event
of a positive result, their specificity was confirmed via immunohistochemic staining
on transfected HEK (human embryonic kidney)-293-cells and preincubation
experiments. IgG subclasses and antibody titers in human material were analysed
and complement binding to the autoantibodies, also under the influence of
therapeutic immunoglobulins (IVIG), was investigated in cell based assays and
ELISA based assays. Clinical features and therapy response in antibody-positive
patients were evaluated and compared to the experimental results.
IgG-autoantibodies against contactin-1 were found in four patients with CIDP,
IgG-autoantibodies against caspr were found in one patient with CIDP and one
with GBS. No further autoantibodies were detected neither in patients with CIDP,
GBS and MMN nor in the controls. The prevalences of autoantibodies against
axoglial paranodal proteins in this study therefore are at 4,76% in CIDP and GBS
and 0% in MMN. In the acute phase of the disease, autoantibodies of the IgG1
and IgG3 subclass could be detected (in two CIDP patients with anti-contactin-1
antibodies and one GBS patient with anti-caspr antibodies), whereas patients in
the chronic phase of the disease showed IgG4-autoantibodies (two CIDP patients with anti-contactin-1 antibodies and one CIDP patient with anti-caspr antibodies).
Complement binding and activation in vitro depended on the amount of the IgG
subclasses IgG1-IgG3, but not IgG4. Complement binding could be reduced by
IVIG dose-dependently. All CIDP-patients with autoantibodies showed a GBSlike
onset with severe motor involvement. Additional features of anti-contactin-1
positive neuropathy were ataxia and tremor, of anti-caspr positive disease neuropathic
pain. Electrophysiological studies revealed signs of conduction failure
accompanied by striking signs of axonal damage. As a histopathologic correlate,
a disruption of the nodal architecture and axonal loss were found. Patients only
responded well to IVIG in the beginning of the disease. Three patients with autoantibodies
of the IgG4 subclass (two patients with anti-contactin-1 and one patient
with anti-caspr) were treated with rituximab, leading to a titer reduction accompanied
by clinical and electrophysiological improvement in two patients.
The screening methods used in this study are suitable for the detection of autoantibodies
against paranodal proteins. Antibody-positive patients define a small
subgroup of patients with inflammatory polyneuropathy that is characterized by
distinct clinical features. Histopathological findings and therapy response to antibody-
depleting treatment in this study as well as findings of further studies argue
in favour of a pathogenetic relevance of the autoantibodies. Neuropathies associated
with paranodal autoantibodies could belong to the new entity of nodo-paranodopathies,
sharing a characteristic pathomechanism with the node of Ranvier
being the site of attack. Complement binding and activation as well as response
to IVIG could be related to the predominant IgG subclass of the autoantibodies.
It could also influence the course and chronification of the disease. Therefore,
detection of autoantibodies against paranodal proteins might have a direct impact
on diagnostic and therapeutic strategies in patients with CIDP and GBS in the
future. Nevertheless, further clinical and experimental data, including data from
bigger and prospective studies are needed to understand and fully characterize
this novel entity.
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Neurophysiological findings in Guillain-Barré syndrome at different stages, a retrospective studyNorling, Maja January 2021 (has links)
Introduction: Guillain-Barré syndrome (GBS) is a neurological disease caused by an autoimmune attack on the peripheral nerves. The main symptoms are loss of motor and sensory skills in the upper and lower extremities. Autonomic dysfunction also occurs.Aim: To identify which parameters in neurography examination that are showing pathology at three different stages from the onset of symptoms. To practically perform and evaluate different electrode placements at RR-intervals.Materials and methods: The first part of this study was a retrospective study with results from 58 patients which were diagnosed with GBS in 2010-2020 at the University Hospital in Uppsala. The second part of this study included measurement of the heart rate variation with RR-intervals at different electrode placement in ten healthy volunteers. Results: In part 1 of the project, there were no significant differences between the groups at distal latency in the ulnar nerve, F-latency in the tibial nerve and in the conduction velocity in the sural nerve. However, there were significant differences in the amplitude of the radial nerve. In part 2 of the project, there were significant differences between the electrode placements, and most artifacts were found with electrodes placed on the shoulders.Conclusion: Examination with neurography and RR-intervals plays an important role in the diagnosis of GBS. As the amplitude in the radial nerve was the only one that showed significant differences between the groups, the nerve is recommended to be examined bilaterally. With a high presence of artifacts in RR-intervals with electrodes placed on the shoulders and wrists, placement on the chest is to be recommended.
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Concomitant Guillain-Barre Syndrome with COVID-19Morongell, Skylar A 01 January 2021 (has links)
The current Coronavirus disease 2019 (COVID-19) outbreak, caused by a virus called severe acute respiratory syndrome 2 (SARS-CoV-2), has become a global health emergency. Recent findings in case studies assert that the transmigration of SARS-CoV-2 to the nervous system implicates severe neurotropic pathologies, including the onset of the rare autoimmune disease called Guillain-Barré syndrome (GBS). GBS is recognized as several disorders characterized by immune-mediated polyradiculoneuropathy, which is typically preceded by an infection or other immune stimulation. The symptoms of GBS initially present as acute symmetrical ascending paresthesia, weakness, and paralysis.
This meta-analysis serves to help understand the predisposing factors (such as gender, age, comorbidities) and the clinical features of COVID-19- induced GBS. Most patients affected were 40 years or older and comprised 78.2% of all the cases. Males comprised most of the cases (62.8%; n=76). The patient mortality was 9.1%, intensive care unit (ICU) admission was 46.6%, and the need for mechanical ventilation was 35.8%. It was found that concomitant GBS and COVID-19 patients most often presented with increased cerebral spinal fluid (CSF) protein levels (88%; n=106), hyporeflexia or areflexia (87.6%) (n=106), lower limb strength and sensation impairment (91.7%; n=111), upper limb strength and sensation impairment (83.5; n=101), and somatic sensation impairment (73.6%; n=89).
It is postulated that COVID-19 triggers the onset of GBS through a “cytokine release storm” (CRS) that occurs in the early stages of the disease. The same cytokines and chemokines involved in this CRS caused by COVID-19 contribute to the onset of GBS. Predisposing factors which influence this concomitance include male gender and older age. Most of the reported symptoms included abnormal limb functions (including paresthesia, weakness, and paralysis) and absent or weak deep tendon reflexes. The most common variant of GBS observed was AIDP, and the most significant laboratory finding among patients was high CSF protein levels.
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Mechanisms in inflammatory demyelinating diseases of the nervous system : immunological and methodological aspects /Kvarnström, Maria, January 2005 (has links) (PDF)
Diss. (sammanfattning) Linköping : Linköpings universitet, 2005. / Härtill 4 uppsatser.
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