PTPN22 1858C&gt;T gene polymorphism in patients with SLE: association with serological and clinical results

Ostanek, Lidia; Ostanek-Pańka, Magdalena; Bobrowska-Snarska, Danuta; Bińczak-Kuleta, Agnieszka; Fischer, Katarzyna; Kaczmarczyk, Mariusz; Ciechanowicz, Andrzej; Brzosko, Marek

doi:10.1007/s11033-014-3498-6

Cited by 18 publications

(13 citation statements)

References 22 publications

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“…The association with SLE has now been replicated in nearly 20 studies, and 2 recent meta‐analyses showed an overall odds ratio of ~1.5 . SLE patients with an 1858T allele were noted in different studies to have higher interferon‐α (IFNα) levels and lower TNF levels , somewhat more prevalent nephritis , and a higher incidence of antiphospholipid syndrome with anticardiolipin autoantibodies .…”

Section: Ptpn22 In Slementioning

confidence: 95%

The Contribution of PTPN22 to Rheumatic Disease

Mustelin

Bottini

Stanford

2019

Arthritis & Rheumatology

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One of the unresolved questions in modern medicine is why certain individuals develop a disorder such as rheumatoid arthritis (RA) or lupus, while others do not. Contemporary science indicates that genetics is partly responsible for disease development, while environmental and stochastic factors also play a role. Among the many genes that increase the risk of autoimmune conditions, the risk allele encoding the W620 variant of protein tyrosine phosphatase N22 (PTPN22) is shared between multiple rheumatic diseases, suggesting that it plays a fundamental role in the development of immune dysfunction. Herein, we discuss how the presence of the PTPN22 risk allele may shape the signs and symptoms of these diseases. Besides the emerging clarity regarding how PTPN22 tunes T and B cell antigen receptor signaling, we discuss recent discoveries of important functions of PTPN22 in myeloid cell lineages. Taken together, these new insights reveal important clues to the molecular mechanisms of prevalent diseases like RA and lupus and may open new avenues for the development of personalized therapies that spare the normal function of the immune system.Dr. Bottini's work was supported by the NIH (grants R01-AI-070544 and R01-AR-066053).

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Section: Ptpn22 In Slementioning

confidence: 95%

The Contribution of PTPN22 to Rheumatic Disease

Mustelin

Bottini

Stanford

2019

Arthritis & Rheumatology

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“…A missense C1858T single‐nucleotide polymorphism (SNP) in PTPN22 encodes an arginine‐to‐tryptophan substitution–bearing protein variant (R620W or LypW) that confers disease risk. Although LypW carriage is associated with modestly altered frequencies of antiphospholipid antibodies and renal disease in SLE patients, clinical phenotypes do not offer strong clues to the mechanism(s) whereby the variant increases disease risk .…”

mentioning

confidence: 99%

PTPN22 Variant R620W Is Associated With Reduced Toll‐like Receptor 7–Induced Type I Interferon in Systemic Lupus Erythematosus

Wang

Ewart

Crabtree

et al. 2015

Arthritis & Rheumatology

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Objective Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) is associated with an increased risk of systemic lupus erythematosus (SLE). PTPN22 encodes Lyp, and a disease‐associated coding variant bears an R620W substitution (LypW). LypW carriage is associated with impaired production of type I interferon (IFN) by myeloid cells following Toll‐like receptor (TLR) engagement. The aim of this study was to investigate the effects of LypW carriage on TLR signaling in patients with SLE. Methods Plasma IFNα concentrations and whole‐blood IFN gene scores were compared in SLE patients who were LypW carriers and those who were noncarriers. TLR‐7 agonist R848–stimulated IFNα and tumor necrosis factor levels, IFN‐dependent gene expression, and STAT‐1 activation were determined in peripheral blood mononuclear cells (PBMCs) and/or plasmacytoid dendritic cells (PDCs) obtained from these patients. The effect of LypW expression on the systemic type I IFN response to R848 stimulation in vivo was assessed in transgenic mice. Results Plasma IFNα levels and whole‐blood IFN gene signatures were comparable in SLE patients who were LypW carriers and those who were noncarriers. However, PBMCs from LypW carriers produced less IFNα and showed reduced IFN‐dependent gene up‐regulation and STAT‐1 activation after R848 stimulation. The frequency of PDCs producing IFNα2 and the per‐cell IFNα2 levels were significantly reduced in LypW carriers. LypW‐transgenic mice displayed reduced TLR‐7–induced circulating type I IFN responses. Conclusion PDCs from SLE patients carrying the disease‐associated PTPN22 variant LypW showed a reduced capacity for TLR‐7 agonist–induced type I IFN production, even though LypW carriers displayed systemic type I IFN activation comparable with that observed in noncarriers. LypW carriage identifies SLE patients who may harbor defects in TLR‐ and PDC‐dependent host defense or antiinflammatory functions.

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“…PTPN22 C1858T polymorphism has been associated with the pathogenesis of SLE in various populations ( Table 7). This polymorphism is significantly associated with susceptibility to SLE in American [116][117][118], Columbian [86,87], Crete [119], Spanish [96], Swedish [120], Polish [121,122], Egyptian populations [123,124].…”

Section: Systemic Lupus Erythematosusmentioning

confidence: 99%

The Protein Tyrosine Phosphatase Non-Receptor Type 22 (PTPN22) Gene Polymorphism and Susceptibility to Autoimmune Diseases

Huraib¹,

Harthi²,

Arfin³

et al. 2020

The Recent Topics in Genetic Polymorphisms

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The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene located on chromosomes 1p 13.3-13 encodes a lymphoid-specific tyrosine phosphatase (Lyp) which is involved in autoimmunity by preventing spontaneous T-cell activation and T-cell development and inactivating T-cell receptor-associated kinases and their substrates. Several single nucleotide polymorphisms (SNPs) have been identified in PTPN22, but only one PTPN22 C1858T has been intensively studied in relation to autoimmune diseases. The PTPN22 C1858T functional polymorphism is a strong non-HLA risk factor for several autoimmune diseases and considered to play an important role in etiology of diseases due to significant production of autoantibodies. However, available literature on PTPN22 C1858T polymorphism and autoimmune diseases shows inconsistencies and ethnic variations. Therefore, further genetic studies on patients suffering from various autoimmune diseases from different ethnicities and PTPN22 gene polymorphisms are expected to help better understand the pathogenesis and will contribute to the development of more targeted therapies and biomarkers.

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PTPN22 1858C>T gene polymorphism in patients with SLE: association with serological and clinical results

Cited by 18 publications

References 22 publications

The Contribution of PTPN22 to Rheumatic Disease

The Contribution of PTPN22 to Rheumatic Disease

PTPN22 Variant R620W Is Associated With Reduced Toll‐like Receptor 7–Induced Type I Interferon in Systemic Lupus Erythematosus

The Protein Tyrosine Phosphatase Non-Receptor Type 22 (PTPN22) Gene Polymorphism and Susceptibility to Autoimmune Diseases

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