The aggregation between AITD with rheumatologic, or dermatologic, autoimmune diseases

Fallahi, Poupak; Elia, Giusy; Ragusa, Francesca; Ruffilli, Ilaria; Camastra, Stefania; Giusti, Claudia; Paparo, Sabrina Rosaria; Gonnella, Debora; Shoenfeld, Yehuda; Ferrari, Silvia; Antonelli, Alessandro

doi:10.1016/j.beem.2019.101372

Cited by 19 publications

(17 citation statements)

References 89 publications

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“…Both GD and RA occur more often in women than in men. A female to male ratio of 6:1 was found in GD, while it is approximately 3:1 in RA (4,9,33). The female karyotype includes two X chromosomes, one of which is randomly silenced during embryogenesis through epigenetic mechanisms, especially DNA methylation.…”

Section: Discussionmentioning

confidence: 99%

Graves’ Disease and Rheumatoid Arthritis: A Bidirectional Mendelian Randomization Study

Xian

Hong

et al. 2021

Front. Endocrinol.

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BackgroundThe frequent coexistence of Graves’ disease (GD) and rheumatoid arthritis (RA) has been cited and discussed in observational studies, but it remains a question as to whether there is a causal effect between the two diseases.MethodsWe retrieved genome-wide association study (GWAS) summary data of GD and RA from BioBank Japan (BBJ). Single nucleotide polymorphisms (SNPs) associated with diseases of interest were selected as instrumental variables (IVs) at a genome-wide significance level (P < 5.0 × 10−8). The random-effects inverse variance weighted method (IVW) was used to combine the causal effect of IVs. The horizontal pleiotropy effect was analyzed by MR-Egger and weighted median method sensitivity test. A leave-one-out analysis was conducted to avoid bias caused by a single SNP. The statistical power of our MR result was calculated according to Brion’s method.ResultsOur study discovered a bidirectional causal effect between GD and RA. The presence of RA may increase the risk of GD by 39% (OR 1.39, 95% CI 1.10–1.75, P = 0.007). Similarly, the existence of GD may increase the risk of RA by 30% (OR 1.30, 95% CI 0.94–1.80, P = 0.112). Our study provides 100% power to detect the causal effect of RA on GD risk, and vice versa.ConclusionsWe found a bidirectional causal effect between GD and RA in an Asian population. Our study supported the clinical need for screening GD in RA patients, and vice versa. The potential benefit of sound management of RA in GD patients (or GD in RA patients) merits excellent attention. Moreover, novel satisfactory medicine for RA may be applicable to GD and such potential is worthy of further investigation.

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Section: Discussionmentioning

confidence: 99%

Graves’ Disease and Rheumatoid Arthritis: A Bidirectional Mendelian Randomization Study

Xian

Hong

et al. 2021

Front. Endocrinol.

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“…Polyautoimmunity is a common feature of thyroid AIDs and the genetic basis of such pleiotropy is partially understood [ 1 , 4 ]. Genetic associations of low-penetrance loci are extensively shared between AIDs [ 8 , [21] , [22] , [23] , [24] ].…”

Section: Discussionmentioning

confidence: 99%

“…The initial phase of Hashimoto thyroiditis is characterized by lymphocytic infiltration into thyroid follicles followed by their gradual destruction; antibodies against thyroid peroxidase or thyroglobulin are often found but whether they contribute to the disease mechanism or are consequences thereof remains unestablished [ 1 , 3 ]. These diseases are associated with each other and many other AIDs presenting examples of polyautoimmunity [ 1 , 4 ]. Both of the diseases are much more common in women than in men.…”

Section: Introductionmentioning

confidence: 99%

Familial risks between Graves disease and Hashimoto thyroiditis and other autoimmune diseases in the population of Sweden

Thomsen

Sundquist

et al. 2020

Journal of Translational Autoimmunity

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Genetic and family studies have indicated that Graves disease and Hashimoto thyroiditis have a heritable component which appears to be shared to some extend also with some other autoimmune diseases (AIDs). In the present nation-wide study we describe familial risk for Graves disease and Hashimoto thyroiditis identified from the Swedish Hospital Discharge Register (years 1964 through 2012) and the Outpatient Register (2001 through 2012). Family relationships were obtained from the Multigeneration Register and cancers from the Cancer Registry. Familial standardized incidence ratios (SIRs) were calculated for 29,005 offspring with Graves disease and for 25,607 offspring with Hashimoto thyroiditis depending on any of 43 AIDs in parents or siblings. The concordant familial risks for Graves disease and Hashimoto thyroiditis were 3.85 and 4.75, higher for men than for women. The familial risks were very high (11.35, Graves and 22.06, Hashimoto) when both a parent and a sibling were affected. Spousal familial risks were higher for Hashimoto thyroiditis (1.98/1.93) than for Graves disease (1.48/1.50). For Graves disease, 24 discordant AIDs showed a significant association; for Hashimoto thyroiditis, 20 discordant associations were significant. All significant discordant associations were positive for the two thyroid AIDs, with the exception of Hashimoto thyroiditis with Reiter disease. Overall 8 associations were significant only for Graves disease and 6 Hashimoto thyroiditis. The overall high concordant familial risks for Graves disease and Hashimoto thyroiditis suggest a strong genetic contribution to the familial risk. Significant familial associations among more than half of the 43 AIDs attest to the extensive polyautoimmunity among thyroid AIDs.

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“…Polyautoimmunity is a common feature of many AIDs, and particularly among rheumatoid and thyroid AIDs [ 30 , 31 ]. The present results attest to shared familial risks between RAIDs, because RA was associated with all other RAIDs, and SLE and SSc were associated with four of five discordant RAIDs.…”

Section: Discussionmentioning

confidence: 99%

Familial associations for rheumatoid autoimmune diseases

Thomsen

Sundquist

et al. 2020

Rheumatology Advances in Practice

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Objectives Previous studies have shown a familial component in rheumatoid arthritis (RA) and in some other rheumatic autoimmune diseases (RAIDs) but because of various study designs the risk estimates for familial risks differ extensively. Methods We collected data on patients diagnosed in Swedish hospitals with RA, ankylosing spondylitis (AS), polymyosistis/dermatomyosistis (PM/DM), Sjogren syndrome (SS), systemic lupus erythematosus (SLE) and systemic sclerosis (SyS, scleroderma) and calculated familial standardized incidence ratios (SIRs) for each of these (concordant) and between them (discordant). Results The combined number of RAID patients in the offspring population (for whom SIRs were calculated) was 71,544 and in the whole population the number was 152,714, accounting for 19.8% of all AIDs in Sweden. AS showed the highest concordant familial risk of 18.42, followed by SLE (14.04), SS (8.63), SyS (4.50), PM/DM (4.03) and RA (3.03). There were no sex difference in SIRs. Risks for AS and SLE were 80.28 and 19.53 for persons whose parents and siblings were affected. Discordant risks were far lower than concordant risks but they were significant for RA with all other 5 RAIDs, for SLE and SyS with 4 RAIDs, for AS and SS with 3 RAIDs and for PM/DM with 2 RAIDs, attesting to extensive polyautoimmunity between RAIDs. Conclusions The derived familial risks in this nation-wide family study on medically diagnosed RAID are compatible with emerging evidence on the polygenic background of these complex diseases. Novel genetic pathways offer new therapeutic targets that optimally alleviate disease onset in high-risk familial patients and others.

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The aggregation between AITD with rheumatologic, or dermatologic, autoimmune diseases

Cited by 19 publications

References 89 publications

Graves’ Disease and Rheumatoid Arthritis: A Bidirectional Mendelian Randomization Study

Graves’ Disease and Rheumatoid Arthritis: A Bidirectional Mendelian Randomization Study

Familial risks between Graves disease and Hashimoto thyroiditis and other autoimmune diseases in the population of Sweden

Familial associations for rheumatoid autoimmune diseases

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