Association between parental autoimmune disease and atopic dermatitis in their offspring: a matched case–control study

Hamann, Carsten R.; Egeberg, Alexander; Silverberg, Jonathan I.; Gislason, Gunnar; Skov, Lone; Thyssen, Jacob P.

doi:10.1111/jdv.15413

Cited by 6 publications

(12 citation statements)

References 76 publications

(165 reference statements)

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“…Maternal systemic lupus erythematosus has been associated with child asthma, anaphylaxis, and other allergic conditions in a few reports 2,3 . Studies have found that the relationship between parental autoimmune disease and child allergy is either maternal‐specific, 22 or related to both maternal and paternal disease 19 …”

Section: Discussionmentioning

confidence: 99%

Maternal autoimmune disease and risk of hospitalization for autoimmune disease, allergy, and cancer in offspring

Zhao

Bégin

Kang

et al. 2022

Pediatric Allergy Immunology

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Background Children whose mothers have autoimmune disease may be at risk of developing immune‐mediated disorders. We assessed the association between maternal autoimmune disease and risk of autoimmune disease, allergy, and cancer in offspring. Methods We analyzed a cohort of 1,011,623 children born in Canada between 2006 and 2019. We identified mothers who had autoimmune diseases and assessed hospitalizations for autoimmune disease, allergy, and cancer in offspring between birth and 14 years of age. We estimated hazard ratios (HR) for the association of maternal autoimmune disease with child hospitalization in adjusted Cox regression models. We used within‐sibling analysis to control for genetic and environmental confounders. Results A total of 20,354 children (2.0%) had mothers with an autoimmune disease. Compared with no autoimmune disease, maternal autoimmune disease was associated with the risk of childhood hospitalization for autoimmune disease (HR 1.96, 95% CI 1.66–2.31) and allergy (HR 1.30, 95% CI 1.21–1.40), but was not significantly associated with cancer (HR 1.31, 95% CI 0.96–1.80). Type 1 diabetes, celiac disease, inflammatory arthritis, and systemic lupus erythematosus were among specific maternal autoimmune diseases most strongly associated with childhood hospitalization for autoimmune disease and allergy. The associations disappeared after controlling for genetic and environmental confounders in the within‐sibling analysis. Conclusions Maternal autoimmune disease is associated with an increased risk of autoimmune disease and allergy hospitalization in offspring, but the relationship appears to be confounded by genetic and environmental factors. Prenatal exposure to immunologic or pharmacologic products is not likely a direct cause of immune‐mediated disease in children.

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Section: Discussionmentioning

confidence: 99%

Maternal autoimmune disease and risk of hospitalization for autoimmune disease, allergy, and cancer in offspring

Zhao

Bégin

Kang

et al. 2022

Pediatric Allergy Immunology

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“…In addition, HLA polymorphisms have also been reported to be associated with AA severity. 11,22,23 The current study showed a higher risk of autoimmune outcomes in offspring born to mothers with AT/AU than in offspring born to mothers with PA.…”

Section: Discussionmentioning

confidence: 50%

“…Several studies have shown a strong association between HLA antigens and AA. 11,[17][18][19][20] It has been shown that HLA polymorphisms may act as susceptibility factors. In addition, coding for the HLA DRB1 allele and related gene variants affects cytokines and toll-like receptors, which in turn influences the patho-genesis of atopic disorders due to the innate/adaptive immune response.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have reported that polymorphisms in the interleukin-1 (IL-1) receptor antagonist gene are associated with AA and the severity of AA. 11,24,25 In addition to IL-1, differences in the polymorphism of the gene controlling tumor necrosis factor-α (TNFα), regulatory T cells (treg cells), cytotoxic T lymphocyteassociated antigen 4 (CTLA4), IL-2/IL-21, IL-2RA (CD25), and eos (Ikaros family zinc finger 4, IKZF4) have been reported in patients with AA. 2,18 In our subgroup analysis, the risk of autoimmune outcomes further increased if offspring had at least 1 sibling with AA.…”

Section: Discussionmentioning

confidence: 99%

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Autoimmune, Inflammatory, Atopic, Thyroid, and Psychiatric Outcomes of Offspring Born to Mothers With Alopecia Areata

Lee

Han

et al. 2023

JAMA Dermatol

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ImportanceAlopecia areata (AA) is associated with diverse autoimmune and psychiatric disorders. However, an investigation on the long-term outcomes for offspring born to mothers diagnosed with AA is lacking.ObjectiveTo investigate the risks for autoimmune, inflammatory, atopic, thyroid, and psychiatric outcomes of offspring born to mothers with AA.Design, Setting, and ParticipantsThis retrospective population-based birth cohort study used the linked birth registration database with the Nationwide Health Insurance Service database of Korea. The participants included all newborns born to mothers with 3 or more visits with International Classification of Diseases, Tenth Revision code of L63 and 1:10 birth year, sex, insurance, income, and location of residence–matched control offspring born to mothers without AA during the years from 2003 to 2015. The analysis was conducted from July 2022 to January 2023.ExposureMaternal AA.Main Outcomes and MeasuresThe occurrence of the following diseases was measured in newborns from birth to December 31, 2020: AA, alopecia totalis/universalis (AT/AU), vitiligo, psoriasis, inflammatory bowel disease, rheumatoid arthritis, atopic dermatitis, allergic rhinitis, asthma, hyperthyroidism, hypothyroidism, Graves disease, Hashimoto thyroiditis, attention-deficit hyperactivity disorder, mood disorder, and anxiety disorder. Multivariable Cox proportional hazard analyses were performed with the following covariates: birth year, age, insurance type, income level, location of residence, maternal age, mode of delivery, maternal history of atopic disorders, and autoimmune disorders.ResultsIn total, 67 364 offspring born to 46 352 mothers with AA and 673 640 controls born to 454 085 unaffected mothers were analyzed. The risk of AA (adjusted hazard ratio [aHR], 2.08; 95% CI, 1.88-2.30), AT/AU (aHR, 1.57; 95% CI, 1.18-2.08), vitiligo (aHR, 1.47; 95% CI, 1.32-1.63), atopic disorders (aHR, 1.07; 95% CI, 1.06-1.09), hypothyroidism (aHR, 1.14; 95% CI, 1.03-1.25), and psychiatric disorders (aHR, 1.15; 95% CI, 1.11-1.20) was significantly increased in offspring born to mothers with AA. Among them, 5088 born to mothers with AT/AU were at much greater risk for the development of AT/AU (aHR, 2.98; 95% CI, 1.48-6.00) and psychiatric disorders (aHR, 1.27; 95% CI, 1.12-1.44).Conclusions and RelevanceIn this Korean retrospective population-based birth cohort study, maternal AA was associated with the development of autoimmune/inflammatory, atopic, thyroid, and psychiatric disorders in their offspring. Clinicians and parents need to be aware of the potential for these comorbidities to occur.

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“…Atopy has been associated with classical autoimmune disorders and AD may co-occur with autoimmune diseases (psoriasis, rheumatoid arthritis, multiple sclerosis and type I diabetes mellitus). In a matched case–control study, including 8589 children with diagnosed AD before the age of 5 and 85,890 controls, the association between parental autoimmune disease and the development of AD in their offspring were studied [ 25 ]. The presence of maternal (not paternal), dermatologic or digestive autoimmune disease was associated with an increased risk for development of AD in their offspring.…”

Section: The Association Of Atopic Dermatitis and Autoimmunitymentioning

confidence: 99%

IgE autoantibodies and autoreactive T cells and their role in children and adults with atopic dermatitis

Badloe

Vriese

Coolens

et al. 2020

Clin Transl Allergy

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The pathophysiology of atopic dermatitis (AD) is highly complex and understanding of disease endotypes may improve disease management. Immunoglobulins E (IgE) against human skin epitopes (IgE autoantibodies) are thought to play a role in disease progression and prolongation. These antibodies have been described in patients with severe and chronic AD, suggesting a progression from allergic inflammation to severe autoimmune processes against the skin. This review provides a summary of the current knowledge and gaps on IgE autoreactivity and self-reactive T cells in children and adults with AD based on a systematic search. Currently, the clinical relevance and the pathomechanism of IgE autoantibodies in AD needs to be further investigated. Additionally, it is unknown whether the presence of IgE autoantibodies in patients with AD is an epiphenomenon or a disease endotype. However, increased knowledge on the clinical relevance and the pathophysiologic role of IgE autoantibodies and self-reactive T cells in AD can have consequences for diagnosis and treatment. Responses to the current available treatments can be used for better understanding of the pathways and may shed new lights on the treatment options for patients with AD and autoreactivity against skin epitopes. To conclude, IgE autoantibodies and self-reactive T cells can contribute to the pathophysiology of AD based on the body of evidence in literature. However, many questions remain open. Future studies on autoreactivity in AD should especially focus on the clinical relevance, the contribution to the disease progression and chronicity on cellular level, the onset and therapeutic strategies.

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Association between parental autoimmune disease and atopic dermatitis in their offspring: a matched case–control study

Cited by 6 publications

References 76 publications

Maternal autoimmune disease and risk of hospitalization for autoimmune disease, allergy, and cancer in offspring

Maternal autoimmune disease and risk of hospitalization for autoimmune disease, allergy, and cancer in offspring

Autoimmune, Inflammatory, Atopic, Thyroid, and Psychiatric Outcomes of Offspring Born to Mothers With Alopecia Areata

IgE autoantibodies and autoreactive T cells and their role in children and adults with atopic dermatitis

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