scholarly journals Management of severe Graves’ hyperthyroidism in pregnancy following immune reconstitution therapy in multiple sclerosis

2021 ◽  
Author(s):  
Sara Salehi Hammerstad ◽  
Elisabeth G Celius ◽  
Henrik Husby ◽  
Ingvild M Sørensen ◽  
Ingrid E Norheim
Keyword(s):  
Multiple Sclerosis ◽  
Hashimoto Thyroiditis ◽  
Newborn Baby ◽  
Graves Disease ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Normal Thyroid Function ◽  
Increased Risk ◽  
Neonatal Thyrotoxicosis

Abstract Context Alemtuzumab (ALZ), a CD52 monoclonal antibody, is highly efficacious in multiple sclerosis; however, side effects are common. Autoimmune thyroid diseases (Graves’ disease and Hashimoto thyroiditis) is a well-known complication of ALZ. Treatment of ALZ induced Graves’ disease can be challenging, and even more difficult during pregnancy. Case description We present a case of severe ALZ induced Graves’ disease with a rapid increase in TSH receptor antibodies (TRAb 240 IU/L) and thyrotoxicosis in early pregnancy. Treatment with high doses of anti-thyroid medication was needed. There was high risk of both fetal and neonatal thyrotoxicosis. Serial fetal sonography showed normal development. The newborn baby presented high levels of TRAb (240 IU/L) and developed neonatal thyrotoxicosis on day eight. Adequate monitoring, treatment, and follow up of the newborn baby ensured normal thyroid function until disappearance of TRAb, 6 weeks after birth. Conclusion MS patients treated with ALZ may develop severe Graves’ disease with an increased risk of both fetal and neonatal thyrotoxicosis. Close follow up with a multidisciplinary approach is needed to ensure a healthy outcome.

Microparticle-enhanced nephelometric immunoassay of anti-thyroid peroxidase autoantibodies in thyroid disorders

1994 ◽  
Vol 40 (3) ◽  
pp. 442-447 ◽  
Author(s):  
A A Harchali ◽  
P Montagne ◽  
J Ruf ◽  
M L Cuillière ◽  
M C Bene ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Hashimoto Thyroiditis ◽  
Human Thyroid ◽  
Thyroid Peroxidase ◽  
Graves Disease ◽  
Thyroid Disorders ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Human Thyroid Peroxidase ◽  
Antigenic Domains

Abstract Crude thyroid peroxidase extracted from human thyroid microsomes was covalently bound onto polyacrylic and polyfunctional copolymerized microparticles. We observed agglutination of the thyroid peroxidase-microparticle conjugate with 13 monoclonal antibodies (mAbs) specific for epitopes on four different antigenic domains of human thyroid peroxidase (TPO; EC 1.11.1.7), after addition of anti-mouse immunoglobulins. We quantified agglutination by measuring with a specially designed nephelometer the light scattered by the conjugates. This allowed us to develop a microparticle-enhanced nephelometric immunoassay for human anti-TPO autoantibodies (aAbs) with defined epitopic specificity, based on the ability of aAbs to inhibit mAb-induced agglutination. Applied to patients with autoimmune thyroid diseases, this assay confirmed the polyclonality of anti-TPO aAbs and their preferential reactivity toward epitopes located on the A and B antigenic domains of the TPO molecule. The same specificities seem to be present in patients with Hashimoto thyroiditis or Graves disease.

scholarly journals SLC26A4 Variations Among Graves’ Hyper-Functioning Thyroid Gland

2010 ◽  
Vol 29 (2) ◽  
pp. 63-69 ◽  
Author(s):  
Hassen Hadj-Kacem ◽  
Rihab Kallel ◽  
Salima Belguith-Maalej ◽  
Mouna Mnif ◽  
Ilhem Charfeddine ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Direct Sequencing ◽  
Autosomal Recessive Disorder ◽  
Hashimoto Thyroiditis ◽  
Autoimmune Thyroid Diseases ◽  
Allelic Variants ◽  
Systematic Analysis ◽  
Autoimmune Thyroid ◽  
Pcr Rflp ◽  
Exon Junctions

Deleterious mutations ofSLC26A4cause Pendred syndrome (PS), an autosomal recessive disorder comprising goitre and deafness with enlarged vestibular aqueducts (EVA), and nonsyndromic hearing loss (NSHL). However, theSLC26A4hyperactivity was recently associated with the emergence of autoimmune thyroid diseases (AITD) and asthma among human and mouse model. Here, by direct sequencing, we investigate the sequences of the 20 coding exons (2 to 21) of SLC26A4 and their flanking intron-exon junctions among patients affected with Graves' disease (GD) hyperthyroidism. Ten mono-allelic variants were identified, seven of which are intronic and previously unreported. Two, c.898A>C (p.I300L) and c.1061T>C (p.F354S), of the three exonic variants are non synonymous. The p.F354S variant is already described to be involved in PS or NSHL inheritances. The exploration by PCR-RFLP of p.I300L and p.F354S variants among 132 GD patients, 105 Hashimoto thyroiditis (HT), 206 Healthy subjects and 102 families with NSHL have shown the presence of both variants. The p.F354S variation was identified both among patients (1~HT and 3 GD) and healthy subjects (n=5). Whereas, the p.I300L variant was identified only in GD patients (n=3). Our studies provide evidence of the importance of systematic analysis ofSLC26A4gene sequences on models other than deafness. This approach allows the identification of new variants and the review of the pathogenic effects of certain mono-allelic variants reported responsible for PS and NSHL development.

scholarly journals Defect of a subpopulation of natural killer immune cells in Graves’ disease and Hashimoto’s thyroiditis: normalizing effect of dehydroepiandrosterone sulfate

2005 ◽  
Vol 152 (5) ◽  
pp. 703-712 ◽  
Author(s):  
Sebastiano Bruno Solerte ◽  
Sara Precerutti ◽  
Carmine Gazzaruso ◽  
Eleonora Locatelli ◽  
Mauro Zamboni ◽  
...  
Keyword(s):  
Nk Cells ◽  
Hashimoto’S Thyroiditis ◽  
Nk Cell ◽  
Secretory Activity ◽  
Thyroid Diseases ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Tnf Α

Background: The study of the natural killer (NK) immune compartment could provide important findings to help in the understanding of some of the pathogenetic mechanisms related to autoimmune thyroid diseases (Graves’ disease (GD) and Hashimoto’s thyroiditis (HT)). Within this context, it was suggested that alterations in NK cell cytotoxicity (NKCC) and NK production of cytokines might occur in subjects with GD and HT, whereas the normalization of NK functions could potentially contribute to the prevention of the onset or the progression of both diseases. Objective: Due to the hypothesis of alterations in NK in autoimmune thyroid diseases, we were interested to evaluate NKCC in GD and HT patients and to modulate NK function and secretory activity with cytokines and dehydroepiandrosterone sulfate (DHEAS) in an attempt to normalize NK cell defect. Design: We studied 13 patients with recent onset Graves’ disease, 11 patients with Hashimoto’s thyroiditis at first diagnosis and 15 age-matched healthy subjects. Methods: NK cells were concentrated at a density of 7.75 × 106 cells/ml by negative immunomagnetic cell separation and validated by FACScan as CD16 + /CD56 + cells. NK cells were incubated with interleukin-2 (IL-2) and interferon-β (IFN-β) and co-incubated with DHEAS at different molar concentrations for measuring NKCC and the secretory pattern of tumor necrosis factor-α (TNF-α) from NK cells. Results: Lower spontaneous, IL-2- and IFN-β-modulated NKCC was demonstrated in GD and HT patients compared with healthy subjects (P < 0.001). A decrease in spontaneous and IL-2-modulated TNF-α release from NK cells was also found in both groups of patients (P < 0.001). The co-incubation of NK cells with IL-2/IFN-β + DHEAS at different molar concentrations (from 10−8 to 10−5 M/ml/NK cells) promptly normalized NKCC and TNF-α secretion in GD and HT patients. Conclusions: A functional defect of a subpopulation of NK immune cells, involving both NKCC and the secretory activity, was demonstrated in newly-diagnosed GD and HT patients. This defect can be reversed by a dose-dependent treatment with DHEAS. The impairment of NK cell activity in autoimmune thyroid diseases could potentially determine a critical expansion of T/B-cell immune compartments leading to the generation of autoantibodies and to the pathogenesis of thyroid autoimmunity.

Depressive symptoms in a treated multiple sclerosis cohort

2003 ◽  
Vol 9 (6) ◽  
pp. 616-620 ◽  
Author(s):  
Scott B Patten ◽  
Shanika Fridhandler ◽  
Cynthia A Beck ◽  
Luanne M Metz
Keyword(s):  
Multiple Sclerosis ◽  
Depressive Symptoms ◽  
Interferon Beta ◽  
Rating Scale ◽  
Epidemiological Studies ◽  
Treatment Groups ◽  
Increased Risk ◽  
The University ◽  
Depression Ratings

Background: Recent side effect data from clinical trials of interferon beta in multiple sclerosis (MS) have failed to confirm that these medications are associated with an increased risk of depression. However, these studies have used highly selected samples and the results may not be generalizable to real world settings. Methods: C linical data on subjects from southern A lberta who have applied for, or are receiving, public reimbursement for MS treatment are maintained in a database at the University of C algary Multiple Sclerosis C linic. Depression ratings obtained using the C enter for Epidemiological Studies Depression Rating Scale (C ES-D) are included in this database. In the current analysis, these longitudinal data were used to determine whether depressive symptoms were associated with disease-modifying treatments. Results: A t baseline, ratings were available for 163 subjects. Those choosing interferon beta resembled those choosing glatiramer acetate in most respects. During follow-up, no differences were observed in the prevalence or incidence of depression and C ES-D scores were not found to differ between the treatment groups. Conclusions: The failure to identify higher rates of depression both in previous intervention studies and in the current observational study provides confirmation that these drugs are not substantially associated with the occurrence of depression.

Development of Autoimmune Thyroid Disease in Multiple Sclerosis Patients Post-Alemtuzumab Improves Treatment Response

2020 ◽  
Vol 105 (9) ◽  
pp. e3392-e3399 ◽  
Author(s):  
Alina Sovetkina ◽  
Rans Nadir ◽  
Antonio Scalfari ◽  
Francesca Tona ◽  
Kevin Murphy ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Graves Disease ◽  
Autoimmune Thyroid ◽  
Tertiary Referral Center ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
Edss Score ◽  
Multiple Sclerosis Patients

Abstract Context Alemtuzumab is an anti-CD52 monoclonal antibody used in the treatment of relapsing-remitting multiple sclerosis (MS). Between 20% and 40% of alemtuzumab-treated MS patients develop autoimmune thyroid disease (AITD) as a side effect. Objective The objective of this work is to determine whether MS disease progression following alemtuzumab treatment differs in patients who develop AITD compared to those who do not. Design, Setting, and Patients A retrospective analysis of 126 patients with relapsing-remitting MS receiving alemtuzumab from 2012 to 2017 was conducted at a tertiary referral center. Main Outcome Measures Thyroid status, new relapses, Expanded Disability Status Scale (EDSS) score change, and disability progression following alemtuzumab were evaluated. Results Twenty-six percent (33 out of 126, 25 female, 8 male) of alemtuzumab-treated patients developed AITD, 55% of which was Graves disease. EDSS score following alemtuzumab was reduced in patients who developed AITD compared to those who did not (median [interquartile range]; AITD: –0.25 [–1 to 0.5] vs non-AITD: 0 [1-0]. P = .007]. Multivariable regression analysis confirmed that the development of AITD was independently associated with EDSS score improvement (P = .011). Moreover, AITD patients had higher relapse-free survival following alemtuzumab (P = .023). There was no difference in the number of new focal T2 lesions and contrast-enhancing magnetic resonance imaging lesions developed following alemtuzumab between the 2 groups. Conclusion Graves disease was the most common form of AITD developed by MS patients following alemtuzumab. This study suggests that MS patients who develop AITD may have an improved response to alemtuzumab, as measured by reduced disability and lower relapse rate.

scholarly journals Co-occurrence of Relapsing Polychondoritis and Autoimmune Thyroid Diseases

2021 ◽  
Author(s):  
Toshiki Nakajima ◽  
Hajime Yoshifuji ◽  
Yoshihisa Yamano ◽  
Kimiko Yurugi ◽  
Yasuo Miura ◽  
...  
Keyword(s):  
Medical Records ◽  
Relapsing Polychondritis ◽  
Hashimoto Thyroiditis ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Genetic Features ◽  
Significant Enrichment ◽  
Recurrent Inflammation ◽  
Genetic Profiles ◽  
Distinct Subtype

Abstract Background: Relapsing polychondritis (RP) is a rare inflammatory disease characterized by recurrent inflammation and destruction of cartilageous tissues. RP has characteristics of autoimmune disease and some reports have noted co-occurrence with autoimmune thyroid disease (AITD), consisting of Graves’ disease (GD) and Hashimoto thyroiditis (HT). However there have been no detailed studies on the co-occurrence of RP and AITD. In this study, we aimed to determine whether patients with RP tend to be complicated with AITD. We also analyzed clinical and genetic profiles of patients in whom these diseases co-occur.Methods: We recruited 117 patients with RP and reviewed their medical records. Furthermore, we genotyped Human Leucocyte Antigen (HLA)-A, B Cw, DRB1, DQB1 and DPB1 alleles for 93 of the 117 patients. The prevalence of AITD among the patients with RP was compared with that among the general Japanese population. We also analyzed the clinical and genetic features of the patients with both RP and AITD.Results: The prevalence of GD among the patients with RP was 4.3% (5 among 117 patients), significantly higher than that among Japanese (0.11%) (p=2.44×10-7, binomial test). RP patients with GD tended to have nasal involvement (p=0.023) (odds ratio (OR) 2.58) and HLA-DPB1*02:02 (p=0.035, OR 10.41). We did not find significant enrichment of HT in patients with RP.Conclusions: Patients with RP appear to be at elevated risk of GD. Nasal involvement and HLA-DPB1*02:02 may characterize the subset of RP patients with GD, which may guide attempts to characterize distinct subtype of RP for precision medicine.

scholarly journals The role of selenium in the pathogenesis of thyroid disease

2019 ◽  
Vol 14 (4) ◽  
pp. 192-205 ◽  
Author(s):  
Ekaterina A. Troshina ◽  
Evgeniya S. Senyushkina ◽  
Maria A. Terekhova
Keyword(s):  
Immune Response ◽  
Thyroid Disease ◽  
Animal Experiments ◽  
Optimal Level ◽  
Thyroid Diseases ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Increased Risk ◽  
Combined Deficiency

The past few years have been actively discussing the role of individual macro- and micronutrients as factors regulating the functional activity of organs and systems and reducing the risk of developing a number of diseases, including thyroid diseases. Selenium is one of the most important and intensively studied at present microelements. According to several studies, its low plasma level is associated with an increased risk of developing autoimmune thyroid diseases. In animal experiments, it was shown that a combined deficiency of selenium and iodine leads to more pronounced hypothyroidism than iodine deficiency alone. Some authors believe that cretinism in the newborn is a consequence of the combined deficiency of these two elements in the mother. It is also important that the optimal level of selenium is necessary both to initiate an immune response and to regulate an excessive immune response, as well as chronic inflammation. The review article discusses the relationship between selenium and thyroid pathology, discusses the role of selenium in the physiology of the thyroid gland and in the development of autoimmune diseases. The biochemical aspects of the pathogenesis of thyroid disease are presented.

scholarly journals Polymorphisms of IKZF3 Gene and Autoimmune Thyroid Diseases: Associated with Graves’ Disease but Not with Hashimoto’s Thyroiditis

2018 ◽  
Vol 45 (5) ◽  
pp. 1787-1796 ◽  
Author(s):  
Ling Li ◽  
Xiaolian Ding ◽  
Xuan Wang ◽  
Qiuming Yao ◽  
Xiaoqing Shao ◽  
...  
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Zinc Finger Protein ◽  
Thyroid Diseases ◽  
Hashimoto's Thyroiditis ◽  
Control Group ◽  
Graves Disease ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Significant Difference ◽  
Proliferation And Differentiation

Background/Aims: The IKZF3 gene encodes a zinc-finger protein that plays an important role in the proliferation and differentiation of B lymphocytes. Autoimmune thyroid diseases (AITDs), mainly include Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are probably caused by the aberrant proliferation of B cells. The objective of this study was to explore the association between IKZF3 polymorphisms and AITDs. Methods: We examined 915 AITD patients (604 GD and 311 HT) and 814 healthy controls. IKZF3 variants (rs2941522, rs907091, rs1453559, rs12150079 and rs2872507) were tested by PCR-ligase detection reaction. Results: It was manifested that that the minor alleles of the five loci increased susceptibility to GD (p<0.05 for rs2941522, and p<0.01 for rs907091, rs1453559, rs12150079 and rs2872507) but in HT patients, these loci showed no significant difference compared with controls. Similarly, the genotype distributions of GD patients manifested obvious differences in all these loci compared with the control group, whereas no statistical differences were observed between HT patients and controls. Furthermore, bioinformatics tools were used to analyze rs1453559, rs12150079 and rs907091. These variants were believed to be the transcription regulator. Conclusion: It is the first time we reported the association between the IKZF3 polymorphisms and GD, indicating that IKZF3 gene tends to bean important risk factor for the development of GD.

Polymorphisms of IRAK1 Gene on X Chromosome Is Associated with Hashimoto Thyroiditis in Korean Children

Endocrinology ◽  
2020 ◽  
Vol 161 (8) ◽  
Author(s):  
Hye-Ri Shin ◽  
Won Kyoung Cho ◽  
In-Cheol Baek ◽  
Na Yeong Lee ◽  
Yoon Ji Lee ◽  
...  
Keyword(s):  
X Chromosome ◽  
Hashimoto Thyroiditis ◽  
Categorical Variables ◽  
Graves Disease ◽  
Strong Linkage Disequilibrium ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Korean Children ◽  
Autoimmune Thyroid ◽  
Thyroid Associated Ophthalmopathy

Abstract Autoimmune thyroid disease (AITD) is predominant in females and has been focused on the sexual diploid in immune response. The IL-1 receptor-associated kinase 1 (IRAK1) gene on the X chromosome was recently suggested as strong autoimmune disease-susceptible loci, second to the major histocompatibility complex region. We investigated the frequency of IRAK1 single-nucleotide polymorphisms (SNPs) in children with AITD. In this study, we observed that SNPs of IRAK1 including rs3027898, rs1059703, and rs1059702 in 115 Korean AITD pediatric patients (Graves’ disease = 74 [females = 52/males = 22]; Hashimoto disease [HD] = 41 [females = 38/males = 3]; thyroid-associated ophthalmopathy [TAO] = 40 (females = 27/males = 13); without TAO = 75 (females = 63/males = 12); total males = 25, total females = 90; mean age = 11.9 years) and 204 healthy Korean individuals (males = 104/females = 100). The data from cases and controls were analyzed from separate sex-stratified or all combined by χ 2 test for categorical variables and Student t test for numerical variables. Our study revealed that SNPs of IRAK1-associated HD and without TAO but Graves’ disease and TAO were not found significant. When cases and controls were analyzed by separate sex, we found that rs3027898 AA, rs1059703 AA, and rs1059702 GG showed disease susceptibility in female AITD, HD, and without TAO. Also, all rs3027898, rs1059703, and rs1059702 were found to be in strong linkage disequilibrium (D′ = 0.96-0.98, r2 = 0.83–0.97). The haplotype of 3 SNPs was higher in AITD than in controls (CGA, r2 = 5.42, P = 0.019). Our results suggest that IRAK1 polymorphisms may contribute to the pathogenesis of HD, AITD, and without thyroid-associated ophthalmopathy for females.

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