The autoimmune spectrum of myasthenia gravis: a Swedish population‐based study

Fang, Fang; Sveinsson, Ólafur; Thormar, G.; Granqvist, Mathias; Askling, Johan; Lundberg, Ingrid E.; Ye, Wei; Hammarström, Lennart; Pirskanen, Ritva; Piehl, Fredrik

doi:10.1111/joim.12310

Cited by 100 publications

(108 citation statements)

References 33 publications

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“…Prosečna godišnja prevalencija za navedeno razdoblje iznosi 153,6/1.000.000 stanovnika. U svetu se vrednosti standardizovane prevalencije kreću od 27,7/1.000.000 do 354,7/1.000.000 stanovnika (13)(14)(15)(16)(17). Ovakav raspon vrednosti prevalencije mogao bi da se objasni razlikama u dijagnostičkim i terapijskim mogućnostima među zemljama.…”

Section: Diskusijaunclassified

“…Takođe je poznato da osobe koje imaju MG imaju povećan rizik i za javljanje drugog autoimunog oboljenja u odnosu na populaciju bez MG. U literaturi se navode različite učestalosti javljanja autoimunih bolesti udruženih sa MG i iznose 13-23% (9,15,(22)(23)(24). U istraživanju Maoa i saradnika (23) registrovana je učestalost od 13%, koja je najpribližnija rezultatu dobijenom u našoj studiji od 11,9%.…”

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“…Među pacijentima obuhvaćenim našom studijom, autoimune bolesti koje su se najčešće javljale udružene sa MG bile su Hašimoto tireoiditis, SLE, polimiozitis, RA i perniciozna anemija, što je u skladu sa nalazima drugih studija (9,15,23,25,26). Učestalost Hašimoto tireoiditisa iznosila je 4%, a skoro isti podatak (4,2%), dobijen je u studiji sprovedenoj u Japanu na 142 pacijenta sa MG (24).…”

Section: Diskusijaunclassified

“…MedPodml 2017, 68(1): [14][15][16][17][18][19][20] Uvod Stečena autoimuna miastenija gravis (MG) predstavlja autoimuno oboljenje u kome se javljaju antitela na različite postsinaptičke strukture neuromišićne spojnice, uglavnom na nikotinski acetilholinski receptor (nAChR), ali i na mišićno specifičnu tirozin kinazu (MuSK), protein 4 povezan sa lipoproteinom (LRP4) ili arginin (1). Ova antitela uzrokuju oštećenje neuromišićne transmisije i klinički dovode do mišićne slabosti i patološke zamorljivosti.…”

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Frequency of familial occurrence and associated autoimmune diseases in a cohort of patients with acquired autoimmune myasthenia gravis from Belgrade

Josipovic¹,

Jovanović²,

Jadžić³

et al. 2017

Med podmladak

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Introduction: Myasthenia gravis (MG) can be associated with other autoimmune diseases (AID), most frequently with Hashimoto's thyroiditis, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Familial occurrence (FOMG) is rare and it exists in 3.5-4.2% patients with MG. Aim: To determine the occurrence of FOMG, the occurrence of AID associated with MG and to identify potential risk factors for developing MG in a cohort of patients from Belgrade. Material and Methods: This study gathered data from 453 patient histories from the period from1992-2014, from the Clinic of Neurology, Clinical Center of Serbia. Three analyses were performed. The first one measured the frequency of associated AID in patients with MG. In the second one, patients who had MG associated with AID were compared to patients without associated AID. The third one included patients with FOMG and compared them with patients without FOMG. The demographic and clinical characteristics of these patients were analysed and comparisons were made between observed and control groups. Results: The associated AID were present in 54 (11.9%) patients, the most frequent was Hashimoto thyreoiditis (4%), then SLE (1.3%), and RA, polymyositis and pernicious anaemia (0.9%). Patients with co-occurrence of MG and other AID were, in comparison with control group, more often female, and the difference was on the border of statistical significance (p=0.056). They had late onset MG (LOMG) more frequently, a mild form of MG and positive anti-AChR antibodies, but these differences weren't statistically significant. FOMG was seen in 2.2% of patients. They had LOMG more frequently, were predominantly men, seropositive, and with mild form of the disease, but with no statistical significance compared to the control group. Conclusion: In the Belgrade cohort, MG was often associated with other AID, while FOMG was relatively rare. There was no significant difference, statistically, in the observed clinical and demographic characteristics of analysed groups, compared to control groups.

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Frequency of familial occurrence and associated autoimmune diseases in a cohort of patients with acquired autoimmune myasthenia gravis from Belgrade

Josipovic¹,

Jovanović²,

Jadžić³

et al. 2017

Med podmladak

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“…6 On the basis of all these associations, one may argue that our findings may represent a universal feature of autoimmunity rather than being MG specific. These disorders share genetic factors with MG, and there is an increased risk of co-occurrence with MG. 25,26 Focused studies exploring all shared genetic and immunologic pathways are warranted to prove causality and to define the pathomechanisms more narrowly.…”

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Increased risk for clinical onset of myasthenia gravis during the postpartum period

et al. 2016

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Objective: To study the risk of clinical onset of myasthenia gravis (MG) in pregnancy and during the first 6 months postpartum because an association between pregnancy or the postpartum period and the onset of autoimmune MG is widely assumed but not proven. Methods:The design was a cross-sectional population-based cohort study of 2 MG cohorts (Norway and the Netherlands) with 1,038 healthy controls from Norway. Data were obtained on 246 women with MG (age at onset 15-45 years). Data on pregnancy, hormonal factors, and clinical symptoms were collected by a previously validated environmental MG questionnaire. Relative risk of MG onset before, during, and after pregnancy was calculated by multinomial logistic regression for Norwegian women reaching 45 years of age, adjusted for the observed distribution of person-years in the corresponding control group.Results: Of the included women with MG, 13 (11.5%) of the Dutch and 24 (18.0%) of the Norwegian patients had their first myasthenia symptoms during the pregnancy or postpartum period. The postpartum period was confirmed to be significantly associated with the onset of symptoms of MG in Norwegian women with MG (relative risk 5.5, 95% confidence interval 2.6-11.6). The risk was highest after the first childbirth. Autoimmune myasthenia gravis (MG) is hallmarked by fluctuating weakness, fatigability, thymic abnormalities, and antibodies that target proteins at the neuromuscular endplate such as the acetylcholine receptor (AChR) and muscle-specific kinase.1 The early-onset AChR MG subtype (EOMG) typically starts between 20 and 40 years of age and is characterized by a female preponderance (3:1) and thymus hyperplasia with germinal centers.2 EOMG is strongly associated with the haplotype human leukocyte antigen (HLA)-B*08/DRB1*03, but otherwise there are no well-established risk factors.

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Association of Stress-Related Disorders With Subsequent Autoimmune Disease

Song

Fang

Tómasson

et al. 2018

JAMA

303

210

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Psychiatric reactions to life stressors are common in the general population and may result in immune dysfunction. Whether such reactions contribute to the risk of autoimmune disease remains unclear. OBJECTIVE To determine whether there is an association between stress-related disorders and subsequent autoimmune disease. DESIGN, SETTING, AND PARTICIPANTS Population-and sibling-matched retrospective cohort study conducted in Sweden from January 1, 1981, to December 31, 2013. The cohort included 106 464 exposed patients with stress-related disorders, with 1 064 640 matched unexposed persons and 126 652 full siblings of these patients. EXPOSURES Diagnosis of stress-related disorders, ie, posttraumatic stress disorder, acute stress reaction, adjustment disorder, and other stress reactions. MAIN OUTCOMES AND MEASURES Stress-related disorder and autoimmune diseases were identified through the National Patient Register. The Cox model was used to estimate hazard ratios (HRs) with 95% CIs of 41 autoimmune diseases beyond 1 year after the diagnosis of stress-related disorders, controlling for multiple risk factors. RESULTS The median age at diagnosis of stress-related disorders was 41 years (interquartile range, 33-50 years) and 40% of the exposed patients were male. During a mean follow-up of 10 years, the incidence rate of autoimmune diseases was 9.1, 6.0, and 6.5 per 1000 person-years among the exposed, matched unexposed, and sibling cohorts, respectively (absolute rate difference, 3.12 [95% CI, 2.99-3.25] and 2.49 [95% CI, 2.23-2.76] per 1000 person-years compared with the population-and sibling-based reference groups, respectively). Compared with the unexposed population, patients with stress-related disorders were at increased risk of autoimmune disease (HR, 1.36 [95% CI, 1.33-1.40]). The HRs for patients with posttraumatic stress disorder were 1.46 (95% CI, 1.32-1.61) for any and 2.29 (95% CI, 1.72-3.04) for multiple (Ն3) autoimmune diseases. These associations were consistent in the sibling-based comparison. Relative risk elevations were more pronounced among younger patients (HR, 1.48 [95% CI, 1.42-1.55]; 1.41 [95% CI, 1.33-1.48]; 1.31 [95% CI, 1.24-1.37]; and 1.23 [95% CI, 1.17-1.30] for age at Յ33, 34-41, 42-50, and Ն51 years, respectively; P for interaction < .001). Persistent use of selective serotonin reuptake inhibitors during the first year of posttraumatic stress disorder diagnosis was associated with attenuated relative risk of autoimmune disease (HR, 3.64 [95% CI, 2.00-6.62]; 2.65 [95% CI, 1.57-4.45]; and 1.82 [95% CI, 1.09-3.02] for duration Յ179, 180-319, and Ն320 days, respectively; P for trend = .03). CONCLUSIONS AND RELEVANCE In this Swedish cohort, exposure to a stress-related disorder was significantly associated with increased risk of subsequent autoimmune disease, compared with matched unexposed individuals and with full siblings. Further studies are needed to better understand the underlying mechanisms.

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The autoimmune spectrum of myasthenia gravis: a Swedish population‐based study

Abstract: Our results suggest that MG shares risk factors with other autoimmune diseases, to a greater degree than MS, with a particular role of the HLA-B8-DR3 haplotype, especially amongst younger and female patients.

Cited by 100 publications

References 33 publications

Frequency of familial occurrence and associated autoimmune diseases in a cohort of patients with acquired autoimmune myasthenia gravis from Belgrade

Frequency of familial occurrence and associated autoimmune diseases in a cohort of patients with acquired autoimmune myasthenia gravis from Belgrade

Increased risk for clinical onset of myasthenia gravis during the postpartum period

Association of Stress-Related Disorders With Subsequent Autoimmune Disease

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