Allele *2 of the HS1,2A enhancer of the Ig regulatory region associates with rheumatoid arthritis

Tolusso, Barbara; Frezza, Domenico; Mattioli, Claudia; Fedele, Anna Laura; Bosello, Silvia Laura; Faustini, Francesca; Peluso, Giusy; Giambra, Vincenzo; Pietrapertosa, Donatello; Morelli, Alessia; Gremese, Elisa; Santis, Maria De; Ferraccioli, Gianfranco

doi:10.1136/ard.2008.095414

Cited by 24 publications

(31 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since our previous observations have shown that the HS1.2 polymorphism is also associated with IgA deficiency23 24 and an association of the HS1.2 allele *2 has been reported with coeliac disease,19 psoriasis and dermatitis herpetiformis20 and with systemic sclerosis21 and rheumatoid arthritis,22 we believe our findings indicate a definite role as a risk factor in autoimmune diseases. These data thus reinforce the relationship of this heavy chain locus control region with autoimmunity.…”

Section: Discussionsupporting

confidence: 69%

“…The alleles depicted in figure 1 are derived by tandem duplications of a 40 bp satellite DNA from 1–4 copies separated by stretches of ∼15 cytosines. An increased frequency of HS1.2 allele *2 has been associated with several immunological diseases including IgA nephropathy, coeliac disease, psoriasis, systemic sclerosis and rheumatoid arthritis 18–22…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Polymorphisms of the IgH enhancer HS1.2 and risk of systemic lupus erythematosus

et al. 2012

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Polymorphisms of the IgH enhancer HS1.2 and risk of systemic lupus erythematosus

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Furthermore, the 3’ Igh RR has been associated to date with several human immune-related disorders including Burkitt’s lymphoma, and rheumatoid arthritis [17, 18]. Moreover, these same diseases have been associated with oxidative stress and ROI.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen peroxide modulates immunoglobulin expression by targeting the 3′Ighregulatory region through an NFκB-dependent mechanism

Romer

Sulentic

2011

Free Radical Research

View full text Add to dashboard Cite

Reactive oxygen species such as hydrogen peroxide (H2O2) appear to play a role in signal transduction in immune cells and have been shown to be synthesized upon antigen-mediated activation and to facilitate cellular activation in B and T cells. However an effect of H2O2 on B-cell function (i.e. immunoglobulin (Ig) expression) has been less well-characterized. The effects of H2O2 exposure on lymphocytes may be partly mediated by oxidative modulation of the NFκB signal transduction pathway, which also plays a role in Ig heavy chain (Igh) gene expression. Igh transcription in B lymphocytes is an essential step in antibody production and is governed through a complex interaction of several regulatory elements, including the 3’Igh regulatory region (3’IghRR). Utilizing an in vitro mouse B-cell line model, this study demonstrates that exposure to low μM concentrations of H2O2 can enhance 3’IghRR-regulated transcriptional activity and Igh gene expression, while either higher concentrations of H2O2 or the expression of a degradation resistant inhibitory κB (IκBα super-repressor) can abrogate this effect. Furthermore, suppressive H2O2 concentrations increased protein levels of the p50 NFκB subunit, IκBα, and an IκBα immunoreactive band which was previously characterized as an IκBα cleavage product exhibiting stronger inhibitory function than native IκBα. Taken together, these observations suggest that exposure of B lymphocytes to H2O2 can alter Igh transcriptional activity and Ig expression in a complex biphasic manner which appears to be mediated by NFκB and altered 3’IghRR activity. These results may have significant implications to disease states previously associated with the 3’IghRR.

show abstract

“…1B) was found significantly associated to several immune-mediated diseases (32,33). Compared with the healthy population, IGAD subjects have a highly significant increase of allele *1 frequency.…”

mentioning

confidence: 95%

Allele *1 of HS1.2 Enhancer Associates with Selective IgA Deficiency and IgM Concentration

Giambra

Cianci

Lolli

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

Selective IgA deficiency (IGAD) is the most common primary immunodeficiency, yet its pathogenesis is elusive. The IG (heavy) H chain human 3′ Regulatory Region harbors three enhancers and has an important role in Ig synthesis. HS1.2 is the only polymorphic enhancer of the 3′RRs. We therefore evaluated HS1.2 allelic frequencies in 88 IGAD patients and 101 controls. Our data show that IGAD patients have a highly significant increase of homozygousity of the allele *1 (39% in the IGAD patients and 15% in controls), with an increase of 2.6-fold. Allele *4 has a similar trend of allele *2, both showing a significant decrease of frequency in IGAD. No relationship was observed between allele *1 frequencies and serum levels of IgG. However, allele *1 was associated in IGAD patients with relatively low IgM levels (within the 30th lowest percentile of patients). The HS1.2 polymorphism influences Ig seric production, but not IgG switch, in fact 30th lowest or highest percentile of IgG in patients did not associate to different frequencies of HS1.2 alleles. The control on normal healthy subjects did not correlate high or low levels of IgM or IgG with HS1.2 allelic frequence variation. Overall our candidate gene approach confirms that the study of polymorphisms in human diseases is a valid tool to investigate the function of these Regulatory Regions that confers multiple immune features.

show abstract

Allele *2 of the HS1,2A enhancer of the Ig regulatory region associates with rheumatoid arthritis

Cited by 24 publications

References 14 publications

Polymorphisms of the IgH enhancer HS1.2 and risk of systemic lupus erythematosus

Polymorphisms of the IgH enhancer HS1.2 and risk of systemic lupus erythematosus

Hydrogen peroxide modulates immunoglobulin expression by targeting the 3′Ighregulatory region through an NFκB-dependent mechanism

Allele *1 of HS1.2 Enhancer Associates with Selective IgA Deficiency and IgM Concentration

Contact Info

Product

Resources

About