Forward and reverse inheritance — the yin and the yang

Nelson, J. Lee; Lambert, Nathalie

doi:10.1038/nrrheum.2017.88

Cited by 6 publications

(6 citation statements)

References 11 publications

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“…lower levels of SE-Mc with increasing RA-risk score (P = 0.063) ( Fig. 4 B, Right) in agreement with the minigene transfer hypothesis (26,27).…”

Section: Deraa-mc Data Are Not Correlated With Clinical Features Orsupporting

confidence: 82%

“…This was subsequently confirmed and extended with direct demonstration of the SE sequences QKRAA and QRRAA as Mc (33). These studies, considered together with the recent report of increased RA risk in SE-negative women for whom a previously born child had an SE allele (14), bring support to the "minigene transfer" hypothesis whereby patients without risk-associated alleles may nevertheless acquire them through Mc (26,27).…”

Section: Deraa-mc Data Are Not Correlated With Clinical Features Ormentioning

confidence: 61%

“…Pregnancy creates a long-term legacy of microchimerism (Mc), generating a source of acquired alloantigens (26). Mc of fetal origin is unique to women, and Mc with DERAA + HLA (DERAA-Mc) is compelling as an additional source driving molecular mimicry and explaining the paradoxical increase of RA when a child had DERAA in his/her HLA genotype.…”

mentioning

confidence: 99%

“…consequences for their host (31). Associations of Mc have been described with a number of autoimmune diseases (27) and, in risk of RA, Mc strongly depends on the allelic specificity of the acquired alloantigens (26,32,33). Nevertheless, a mechanistic basis for Mc involvement in RA or in the pathogenesis of other autoimmune diseases has been lacking.…”

mentioning

confidence: 99%

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Immunogenicity of a rheumatoid arthritis protective sequence when acquired through microchimerism

Kanaan

Sensoy

Zhen

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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HLA class II genes provide the strongest genetic contribution to rheumatoid arthritis (RA). HLA-DRB1 alleles encoding the sequence DERAA are RA-protective. Paradoxically, RA risk is increased in women with DERAA+ children born prior to onset. We developed a sensitive qPCR assay specific for DERAA, and found 53% of DERAA−/− women with RA had microchimerism (Mc; pregnancy-derived allogeneic cells) carrying DERAA (DERAA-Mc) vs. 6% of healthy women. DERAA-Mc quantities correlated with an RA-risk genetic background including DERAA-binding HLA-DQ alleles, early RA onset, and aspects of RA severity. CD4+ T cells showed stronger response against DERAA+ vs. DERAA− allogeneic cell lines in vitro, in line with an immunogenic role of allogeneic DERAA. Results indicate a model where DERAA-Mc activates DERAA-directed T cells that are naturally present in DERAA−/− individuals and can have cross-reactivity against joint antigens. Moreover, we provide an explanation for the enigmatic observation that the same HLA sequence differentially affects RA risk through Mendelian inheritance vs. microchimeric cell acquisition.

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“…lower levels of SE-Mc with increasing RA-risk score (P = 0.063) ( Fig. 4 B, Right) in agreement with the minigene transfer hypothesis (26,27).…”

Section: Deraa-mc Data Are Not Correlated With Clinical Features Orsupporting

confidence: 82%

Section: Deraa-mc Data Are Not Correlated With Clinical Features Ormentioning

confidence: 61%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Immunogenicity of a rheumatoid arthritis protective sequence when acquired through microchimerism

Kanaan

Sensoy

Zhen

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…These cells or deoxyribonucleic acid (DNA) that are genetically disparate can affect the long-term health of mothers beneficially or adversely [ 28 ]. Foetal microchimerism is considered by Nelson and Lambert (2017) to be akin to “reverse inheritance” [ 28 , 29 ]. Foetal microchimeric cells contribute to the development of RA by either being targets for immune response or by working as effector cells [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Pregnancy loss and the risk of rheumatoid arthritis in Chinese women: findings from the China Kadoorie biobank

Hee

Pang

et al. 2022

BMC Public Health

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Considering the female preponderance of rheumatoid arthritis (RA), and disease onset typically after the reproductive years, pregnancy and childbirth may play a role in the aetiology of the disease. Adverse outcomes of pregnancy have been found to precede the diagnosis of autoimmune diseases, including RA, but the evidence is scant and inconsistent. Therefore, we investigate whether pregnancy loss is associated with the risk of RA in Chinese women. Data from the China Kadoorie Biobank, conducted by the University of Oxford and the Chinese Centre for Disease Control and Prevention, of 299,629 Chinese women who had been pregnant were used. Multivariable logistic regression and stratified analyses were employed to analyse the association between types of pregnancy loss with the risk of RA. Pregnancy loss was significantly associated with increased risk of RA (OR 1.12, 95% CI 1.06–1.18), specifically, spontaneous (OR 1.11, 95% CI 1.03–1.20) and induced abortions (OR 1.11, 95% CI 1.06–1.17). There was no significant association between stillbirth and the risk of RA (OR 1.07, 95% CI 0.97–1.18). The risk of developing RA increases with the number of pregnancy losses: one loss confers an OR of 1.09 (95% CI 1.03–1.16), two an OR of 1.13 (95% CI 1.05–1.20), three or more an OR of 1.19 (95% CI 1.10–1.28) and OR of 1.06 (95% CI 1.03–1.08) for each additional. Spontaneous and induced abortions are associated with an increased risk of RA in Chinese women.

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Autoimmune Disease

Lambert¹

2018

Chimerism

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Forward and reverse inheritance — the yin and the yang

Cited by 6 publications

References 11 publications

Immunogenicity of a rheumatoid arthritis protective sequence when acquired through microchimerism

Immunogenicity of a rheumatoid arthritis protective sequence when acquired through microchimerism

Pregnancy loss and the risk of rheumatoid arthritis in Chinese women: findings from the China Kadoorie biobank

Autoimmune Disease

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