Neural Autoantibody Profile of Primary Achalasia

Kraichely, Robert E.; Farrugia, Gianrico; Pittock, Sean J.; Castell, Donald O.; Lennon, Vanda A.

doi:10.1007/s10620-009-0838-9

Cited by 62 publications

(69 citation statements)

References 29 publications

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“…In addition, 21% had anti-GAD antibodies. The mean number of years from diagnosis to sera collection in this group was only 5 years (Kraichely et al 2009). The mean number of years from diagnosis to sera collection in our achalasia group was 6 years.…”

Section: Significance and Interpretationsmentioning

confidence: 76%

“…Only one of these had documented diabetes. The clinical significance of this finding remains to be ascertained (Kraichely et al 2009). …”

Section: Specificity To Diseasementioning

confidence: 95%

“…Autoantibodies against specific neuronal, glial and muscle antigens studied using radioimmunoprecipitation assays have identified nAChR, VGKC and N-type VGCC antibodies in a subset of primary achalasia patients (Kraichely et al 2009). …”

Section: Detection Of Autoantibodiesmentioning

confidence: 99%

“…Although we included almost all of these antigens, due to time constraints, some autoantibodies were not screened. These included N-type VGCCs, which have been found in primary achalasia, delayed gastric emptying and slow transit constipation (Dhamija et al 2008;Kraichely et al 2009). It is important to point out that the number of targets for autoantibodies is continually growing, an example being previously 'seronegative' cases of myasthenia gravis now recognised as positive for autoantibodies against a muscle-specific receptor tyrosine kinase (MuSK) (Hoch et al 2001;Wolfe et al 2008).…”

Section: Study Limitationsmentioning

confidence: 99%

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The role of humoral autoimmunity in gastrointestinal neuromuscular diseases

Hubball

Martin

Lang

et al. 2009

Progress in Neurobiology

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Dysfunction of the gastrointestinal neuromuscular apparatus (including interstitial cells ofCajal) is presumed to underlie a heterogeneous group of disorders collectively termed gastrointestinal neuromuscular diseases (GINMDs). Humoral (antibody)-mediated autoimmunity directed against ligand-or voltage-gated ion channels or associated proteins involved in neuromuscular transmission is associated with several acquired neuromuscular diseases of the periphery and is now implicated in an increasing number of less well-characterised diseases. Anti-channel antibodies have been reported in small numbers of patients with GINMD, particularly in those with GI dysfunction secondary to an underlying disease such as neoplasia or infection. However, little is known of humoral autoimmunity in primary GINMDs.This thesis investigated the association between anti-channel antibodies and GINMD, and the human GI tract as a potential target of anti-channel antibodies. The presence of antivoltage-and ligand-gated antibodies was investigated in the serum of patients with primary achalasia, enteric dysmotility and intestinal pseudo-obstruction, and in those with GINMD secondary to Chagas' disease. The functional effect of sera from some of these patients on colonic smooth muscle contractility was also characterised. Finally, the distribution of six voltage-gated potassium channels (VGKCs), which serve essential roles in the peripheral and central nervous systems and are known targets of pathological autoantibodies, were investigated in all layers of the human GI tract.Our findings suggest that currently recognised anti-channel antibodies are not a common pathogenic factor in primary GINMDs. Anti-channel antibodies, in particular anti-VGKC antibodies, were however found in a significant number of individuals with Chagas' disease. Furthermore, circulating factors in patients with chagasic GI disease altered GI smooth muscle contractility in vitro which may have pathological relevance to GI

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Section: Significance and Interpretationsmentioning

confidence: 76%

“…Only one of these had documented diabetes. The clinical significance of this finding remains to be ascertained (Kraichely et al 2009). …”

Section: Specificity To Diseasementioning

confidence: 95%

Section: Detection Of Autoantibodiesmentioning

confidence: 99%

Section: Study Limitationsmentioning

confidence: 99%

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The role of humoral autoimmunity in gastrointestinal neuromuscular diseases

Hubball

Martin

Lang

et al. 2009

Progress in Neurobiology

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“…Arq Bras Endocrinol Metab. 2012;56 (9): are the most prevalent etiologies. Although genetics is well known to cause and influence the progression of autoimmune diseases in approximately 79% (1), other environmental factors are known to be involved in the development of autoimmune thyroid diseases: quantity of ingested iodine, stress, drugs, pregnancy and changes in sexual hormones (1,2).…”

Section: Sumáriomentioning

confidence: 99%

Achalasia and thyroid disease: possible autoimmune connection?

Quidute

Freitas²,

Lima³

et al. 2012

Arq Bras Endocrinol Metab

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SUMMARYMany cases have been published showing a co-existence of autoimmune thyroid diseases (AITDs) and other autoimmune diseases. About a quarter of patients with achalasia have a concurrent thyroid disease, most commonly associated with hypothyroidism. Although relatively rare, the association of achalasia and hyperthyroidism requires attention. The physiopathology of Grave's Disease (GD) involves B-and T-mediator lymphocytes, which have an affinity for known thyroid antigens: thyroglobulin, thyroid-peroxidase, and thyrotrophin receptor. Currently, however, the real physiopathogenesis of achalasia continues to be unknown. Some important findings are suggestive of an autoimmune mechanism: significant infiltration of the myoenteric plexus by monocytes, presence of the class II-Human Histocompatibility Complex DQwl antigen and antibodies to myoenteric neurons. The present case reports a patient who, despite testing negative for Chagas' disease, had achalasia, progressed to developing significant wasting and worsening of his quality of life, was later diagnosed with hyperthyroidism. After endoscopic esophageal dilatation and radioiodine ablation of the thyroid gland, there was great improvement in the patient clinical condition. Arq Bras Endocrinol Metab. 2012;56(9):677-82 SUMáRioMuitos casos têm sido publicados mostrando uma coexistência entre as doenças autoimunes da tireoide (DAIT) e outras doenças autoimunes. Cerca de um quarto dos pacientes com acalasia têm doenças da tireoide concomitantemente, sendo a mais comum a associação com hipotireoidismo. Apesar de ser relativamente rara, a associação da acalasia e hipertireoidismo requer atenção. A fisiopatologia da doença de Graves (DG) envolve os linfócitos B e T-mediados, os quais têm afinidade pelos antígenos da tireoide: tireoglobulina, tireoperoxidase e receptor de tireotrofina. Atualmente, a real fisiopatogenia da acalasia continua desconhecida. No entanto, alguns importantes achados em análise são sugestivos de mecanismo autoimune: infiltração significativa do plexo mioentérico pelos monócitos, presença do antígeno-DQwl do Complexo Humano de Histocompatibilidade classe II e presença de anticorpos contra neurô-nios mioentéricos. Este presente caso aborda um paciente que, apesar de testes negativos para doença de Chagas, tem acalasia que progrediu para o desenvolvimento de significativa perda ponderal e piora da sua qualidade de vida, posteriormente, diagnosticado com hipertireoidismo. Após dilatação endoscópica esofágica e ablação da glândula tireoide com radioiodo, houve grande melhora na condição clínica do paciente. Arq Bras Endocrinol Metab. 2012;56(9):677-82

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Autoimmune Epilepsy

Quek¹

2012

Arch Neurol

320

137

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Thirty-two patients with an exclusive (n=11) or predominant (n = 21) seizure presentation in whom an autoimmune etiology was suspected (on the basis of neural autoantibody [91%], inflammatory cerebrospinal fluid [31%], or magnetic resonance imaging suggesting inflammation [63%]) were studied. All had partial seizures: 81% had failed treatment with 2 or more antiepileptic drugs and had daily seizures and 38% had seizure semiologies that were multifocal or changed with time. Head magnetic resonance imaging was normal in 15 (47%) at onset. Electroencephalogram abnormalities included interictal epileptiform discharges in 20; electrographic seizures in 15; and focal slowing in 13. Neural autoantibodies included voltage-gated potassium channel complex in 56% (leucine-rich, glioma-inactivated 1 specific, 14; contactin-associated proteinlike 2 specific, 1); glutamic acid decarboxylase 65 in 22%; collapsin response-mediator protein 5 in 6%; and Ma2, N-methyl-D-aspartate receptor, and ganglionic acetylcholine receptor in 1 patient each.Intervention: Immunotherapy with intravenous methylprednisolone; intravenous immune globulin; and combinations of intravenous methylprednisolone, intravenous immune globulin, plasmapheresis, or cyclophosphamide.Main Outcome Measure: Seizure frequency.Results: After a median interval of 17 months (range, 3-72 months), 22 of 27 (81%) reported improvement postimmunotherapy; 18 were seizure free. The median time from seizure onset to initiating immunotherapy was 4 months for responders and 22 months for nonresponders (P Ͻ .05). All voltage-gated potassium channel complex antibody-positive patients reported initial or lasting benefit (P Ͻ .05). One voltage-gated potassium channel complex antibody-positive patient was seizure free after thyroid cancer resection; another responded to antiepileptic drug change alone. Conclusion:When clinical and serological clues suggest an autoimmune basis for medically intractable epilepsy, early-initiated immunotherapy may improve seizure outcome.

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Neural Autoantibody Profile of Primary Achalasia

Cited by 62 publications

References 29 publications

The role of humoral autoimmunity in gastrointestinal neuromuscular diseases

The role of humoral autoimmunity in gastrointestinal neuromuscular diseases

Achalasia and thyroid disease: possible autoimmune connection?

Autoimmune Epilepsy

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