Antibodies against Proinsulin and Homologous MAP Epitopes Are Detectable in Hashimoto’s Thyroiditis Sardinian Patients, an Additional Link of Association

Niegowska, Magdalena; Paccagnini, Daniela; Burrai, Carlo; Palermo, Mario; Sechi, Leonardo Antonio

doi:10.1371/journal.pone.0133497

Cited by 13 publications

(19 citation statements)

References 33 publications

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“…It is plausible that anti-mycobacterial Abs remain detectable at high levels even after 20 years following LADA diagnosis in a similar way to GADA titers [39], indicating a possible appearance of their peak values at a younger age. In addition, we have previously observed a comparable distribution of Abs targeting the homologous peptides in case of Hashimoto’s thyroiditis with distinct sex-related prevalence [26]. In the present study, responses to MAP antigens were not gender-associated, however Abs positivity in predisposed subjects, especially those assigned as LADA1, may suggest an increased risk for autoimmune thyroiditis.…”

Section: Discussionsupporting

confidence: 52%

Increased seroreactivity to proinsulin and homologous mycobacterial peptides in latent autoimmune diabetes in adults

et al. 2017

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Latent Autoimmune Diabetes in Adults (LADA) is a slowly progressing form of immune-mediated diabetes that combines phenotypical features of type 2 diabetes (T2D) with the presence of islet cell antigens detected in type 1 diabetes (T1D). Heterogeneous clinical picture have led to the classification of patients based on the levels of antibodies against glutamic acid decarboxylase 65 (GADA) that correlate with clinical phenotypes closer to T1D or T2D when GADA titers are high or low, respectively. To date, LADA etiology remains elusive despite numerous studies investigating on genetic predisposition and environmental risk factors. To our knowledge, this is the first study aimed at evaluation of a putative role played by Mycobacterium avium subsp. paratuberculosis (MAP) as an infective agent in LADA pathogenesis. MAP is known to cause chronic enteritis in ruminants and has been associated with autoimmune disorders in humans. We analyzed seroreactivity of 223 Sardinian LADA subjects and 182 healthy volunteers against MAP-derived peptides and their human homologs of proinsulin and zinc transporter 8 protein. A significantly elevated positivity for MAP/proinsulin was detected among patients, with the highest prevalence in the 32-41-year-old T1D-like LADA subgroup, supporting our hypothesis of a possible MAP contribution in the development of autoimmunity.

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Section: Discussionsupporting

confidence: 52%

Increased seroreactivity to proinsulin and homologous mycobacterial peptides in latent autoimmune diabetes in adults

et al. 2017

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“…Out of 56 studies included in the systematic review, 25 were case‐control studies, 24‐47 17 were cohort studies 48‐64 and 14 were cross‐sectional studies 65‐78 . No clinical trials met the criteria used in the systematic review.…”

Section: Resultsmentioning

confidence: 99%

Prevalence of latent and overt polyautoimmunity in autoimmune thyroid disease: A systematic review and meta‐analysis

Botello

Herrán

Salcedo

et al. 2020

Clinical Endocrinology

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Background Thyroid autoimmunity is the most frequent condition involved in polyautoimmunity (PolyA). However, the frequency of latent and overt PolyA in patients with autoimmune thyroid disease (AITD) as the index condition is unknown. Therefore, the purpose of this study was to determine the prevalence of these types of PolyA in patients with AITD as the index condition. Methods This study adhered to the relevant sections of the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) guideline. Searches through MEDLINE, Embase and LILACS were done to find articles in Spanish and English. Relevant vocabulary terms and key terms related to AITD and other autoimmune diseases were used. Two investigators independently screened the eligible studies, extracted data and assessed the quality and risk of bias. Fixed and random effect models were used accordingly. Cluster analysis was used to determine similarities among diseases in the articles included (based on Jaccard index). Results A total of 56 articles fulfilled the inclusion criteria. Of these, 25 were case‐controls, 17 were cohorts, and 14 were cross‐sectional studies. These studies included a total of 47 509 patients. Female was the predominant gender and included 38 950 patients (81.23%, 95% CI: 80.85‐81.60). Graves’ disease (GD) was the most common type of thyroid autoimmunity (69.16%, 95% CI: 68.23‐70.07). Globally, overt PolyA was found in 13.46% of the patients with AITD. This type of PolyA was represented mainly by type 1 diabetes and autoimmune gastritis. Latent PolyA was presented in 17.45% of the patients, and anti‐proinsulin, anti‐parietal cells and dsDNA antibodies were the most common. HT had the highest frequency of overt PolyA in Europe (15.60%, 95% CI: 14.72‐16.53), whereas latent PolyA was most common in patients with GD in Asia (21.03%, 95% CI: 17.76‐24.71). Overt and latent PolyA were associated with gastrointestinal and endocrinological ADs in most of cases and clustered with rheumatological, dermatological and neurological ADs. Conclusions Latent and overt PolyA are common in patients with AITD. These results provide insightful information for early diagnosis and management of concurrent ADs in patients with AITD. Aggregation of ADs in different clusters may help to define different phenotypes associated with thyroid autoimmunity that are critically relevant in clinical settings.

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“…As the specificity of the bacterial peptides applied in our ELISA method achieves a 100% for MAP, we can certainly declare that ELISA-positive subjects were exposed to MAP and not to other environmental mycobacteria. In some previous studies, the association between anti-MAP peptides and autoimmune diseases like CD, type 1 diabetes, multiple sclerosis (MS) and Hashimoto’s thyroiditis have been reported [38–41]. …”

Section: Discussionmentioning

confidence: 99%

Mycobacterium avium subsp. paratuberculosis and associated risk factors for inflammatory bowel disease in Iranian patients

et al. 2017

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BackgroundInflammatory bowel disease (IBD) is described as a relapsing condition with high morbidity and uncertain complex pathogenesis. The association of Mycobacterium avium ssp. paratuberculosis (MAP) with Crohn’s disease (CD) in human has been debated for decades, however there is no confirmed data to verify such relations in Iran. The aim of this study was to investigate risk factors and a possible role of MAP in Iranian patients with CD.MethodsAnti-MAP antibodies were detected in serum of IBD patients and subjects without IBD (nIBD) through ELISA; MAP DNA and viable MAP cells were identified in patients’ biopsies through nested PCR and direct culture methods, respectively. Principal component analysis (PCA) was used to investigate the risk factors in relation to IBD and MAP infection.ResultsPositivity for IS900 PCR was detected in 64% (n = 18) of CD, 33% (n = 10) of ulcerative colitis (UC) and 9.7% (n = 6) of nIBD samples. Live MAP cells were isolated from biopsies of 2 CD patients only. Among 28 patients with CD, 46% (n = 13) and 39% (n = 11) were positive for antibodies against MAP3865c133–141 and MAP3865c125–133 peptides, respectively, whereas much lower seroreactivity was detected in UC subjects accounting for 3% (n = 1) for MAP3865c133–141 and 16.7% (n = 5) for MAP3865c125–133. A high immune reactivity to MAP epitopes among CD patients was positively correlated with consumption of fast food meals and IBD familiarity. For both CD and UC, breastfeeding period and consumption of fruit/vegetables presented negative correlation with the presence of anti-MAP antibodies.ConclusionsThis study provided evidences that high prevalence of MAP DNA and anti-MAP antibodies in CD patients is significantly associated with the development of CD. Despite the role of several factors contributing to IBD, the presence of MAP DNA and anti-MAP antibodies in Iranian CD patients highlights a possible transmission of MAP from animal-derived products to humans.

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Antibodies against Proinsulin and Homologous MAP Epitopes Are Detectable in Hashimoto’s Thyroiditis Sardinian Patients, an Additional Link of Association

Cited by 13 publications

References 33 publications

Increased seroreactivity to proinsulin and homologous mycobacterial peptides in latent autoimmune diabetes in adults

Increased seroreactivity to proinsulin and homologous mycobacterial peptides in latent autoimmune diabetes in adults

Prevalence of latent and overt polyautoimmunity in autoimmune thyroid disease: A systematic review and meta‐analysis

Mycobacterium avium subsp. paratuberculosis and associated risk factors for inflammatory bowel disease in Iranian patients

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