Increased representation of the PTPN22 mutation in patients with immune thrombocytopenia

D’Silva, Karl J.; Zamora, Mathew; Gerlach, John; Schwartz, Kenneth A.

doi:10.1111/j.1538-7836.2010.03954.x

Cited by 12 publications

(9 citation statements)

References 19 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These frequencies are statistically significant compared to controls (3%) (P ¼ 0.002, P ¼ 0.005 and 0.008, respectively) ( Table 3). These results agreed with the results by D'Silva et al [19] who stated that the T-allele frequency in the ITP patients was 15.5% which was statistically different from the allele frequency of 8.7% observed in a population of 926 normal individuals (P ¼ 0.02); however, they found no statistically significant difference in the genotype frequency between the patient and the control group (P ¼ 0.08).…”

Section: Discussionsupporting

confidence: 93%

The role of PTPN22 gene polymorphism in childhood immune thrombocytopenic purpura

Anis

Ghany²,

Mostafa³

et al. 2011

Blood Coagulation &Amp; Fibrinolysis

View full text Add to dashboard Cite

Immune thrombocytopenia is an autoimmune disorder characterized by antibody-mediated platelet destruction. A protein tyrosine phosphatase (PTPN22) present in lymphocytes is an important negative regulator of signal transduction for the T-cell receptor-MHC complex and has been associated with autoimmune disorders that produce autoantibodies. The present study investigated the frequency of the 1858C>T single-nucleotide polymorphism (SNP) in the PTPN22 gene in idiopathic thrombocytopenic purpura (ITP) patients. This case series study included 50 children with ITP, 24 acute and 26 chronic cases, and 50 normal children as a control group. All were subjected to clinical history and laboratory investigations including complete blood count, genotyping of PTPN22 1858C/T SNP by polymerase chain reaction-restriction fragment length polymorphism and platelet antibodies using platelets suspension immunofluorescence test for the cases. Thirteen patients (26%) were positive for the PTPN22 1858C>T SNP. Three patients were homozygous for the mutation and 10 were heterozygous. Comparison of the 26% of the ITP patients who were positive for the PTPN22 1858C>T mutation with the 6% positive in the control group yielded a P value of 0.006. Antiplatelet antibodies were detected in five patients (20.8%) with acute ITP and in three patients (11.5%) with chronic ITP; no significant association between the presence of PTPN22 1858C>T mutation and the presence of antiplatelet antibodies was detected. The prevalence of PTPN22 gene mutation was higher in ITP patients, thus it may be considered as a genetic risk factor in the development of ITP in Egyptian children.

show abstract

Section: Discussionsupporting

confidence: 93%

The role of PTPN22 gene polymorphism in childhood immune thrombocytopenic purpura

Anis

Ghany²,

Mostafa³

et al. 2011

Blood Coagulation &Amp; Fibrinolysis

View full text Add to dashboard Cite

show abstract

“…Association between PTPN22 and other autoimmune diseases Besides the autoimmune diseases mentioned above, an association between PTPN22 and several other autoimmune diseases has been investigated, including ankylosing spondylitis (AS), primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC), idiopathic inflammatory myopathies (IIM), acute anterior uveitis (AAU), immune thrombocytopenia and pemphigus vulgaris (PV). 64,103,[127][128][129][130][131] The results are summarized in Supplementary Table S1. Only one case-control study was conducted for each disease in European populations or populations of European descent, making meta-analysis impossible.…”

Section: Diseases Showing No or Weak Association With Ptpn22mentioning

confidence: 99%

“…Immune thrombocytopenia is characterized by antibody-mediated platelet destruction. D'silva et al 128 reported a strong association between ITP and the PTPN22 T allele in a caucasian US population. This association was confirmed in an Egyptian population.…”

Section: Diseases Showing No or Weak Association With Ptpn22mentioning

confidence: 99%

Meta-analysis reveals an association of PTPN22 C1858T with autoimmune diseases, which depends on the localization of the affected tissue

et al. 2012

View full text Add to dashboard Cite

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a strong susceptibility gene shared by many autoimmune diseases. The aim of this study was to explore the mechanisms underlying this relationship. We performed a comprehensive analysis of the association between PTPN22 polymorphism C1858T and autoimmune diseases. The results showed a remarkable pattern; PTPN22 C1858T was strongly associated with type I diabetes, rheumatoid arthritis, immune thrombocytopenia, generalized vitiligo with concomitant autoimmune diseases, idiopathic inflammatory myopathies, Graves' disease, juvenile idiopathic arthritis, myasthenia gravis, systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody-associated vasculitis and Addison's disease. By contrast, PTPN22 C1858T showed a negligible association with systemic sclerosis, celiac disease, multiple sclerosis, psoriasis, ankylosing spondylitis, pemphigus vulgaris, ulcerative colitis, primary sclerosing cholangitis, primary biliary cirrhosis, Crohn's disease and acute anterior uveitis. Further analysis revealed a clear distinction between the two groups of diseases with regard to their targeted tissues: most autoimmune diseases showing an insignificant association with PTPN22 C1858T manifest in skin, the gastrointestinal tract or in immune privileged sites. These results showed that the association of PTPN22 polymorphism with autoimmune diseases depends on the localization of the affected tissue, suggesting a role of targeted organ variation in the disease manifestations.

show abstract

“…Such genes include the protein tyrosine phosphatase PTPN22 gain-of-function variant, Trp620, which is associated with type 1 diabetes,36 RA, autoimmune thyroid disease, ITP35 and SLE 32. Variants of the signal transducers and activators of transcription-4 (STAT4) genes on chromosome 2q have also recently been associated with SLE and RA,33 Sjögren's syndrome,34 systemic sclerosis59 and type 1 diabetes 37.…”

Section: Genetics: a Common Autoimmune Backgroundmentioning

confidence: 99%

A B cell explanation for autoimmune disease: the forbidden clone returns

McQueen

2012

Postgraduate Medical Journal

View full text Add to dashboard Cite

More than 60 years ago, Burnet first proposed the 'forbidden clone' hypothesis postulating that autoimmune disease arises as a result of persistence of self-reactive clones of lymphocytes that should have been deleted via immune tolerance. These autoreactive clones could effect immune-mediated end-organ damage via peripheral selfantigen recognition. Recent evidence that stretches across the boundaries of many medical specialties supports this proposal, implicating a B cell precursor as the culprit. The success of B cell depleting therapy in rheumatoid arthritis, anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis, polymyositis, lupus and autoimmune diseases as diverse as multiple sclerosis and idiopathic thrombocytopenic purpura supports this proposal. Clonality of B cells and plasma cells has been described in a number of autoimmune disorders and the presence of autoantibodies, which may arise years before the onset of clinical disease, supports the notion of autoreactivity within the B cell lineage. T cell activation within the end-organ would be predicted by cognate BeT cell interactions and resultant tissue inflammation and destruction could produce diverse clinical manifestations dictated by the original specificity of the autoimmune B cell.

show abstract

Increased representation of the PTPN22 mutation in patients with immune thrombocytopenia

Cited by 12 publications

References 19 publications

The role of PTPN22 gene polymorphism in childhood immune thrombocytopenic purpura

The role of PTPN22 gene polymorphism in childhood immune thrombocytopenic purpura

Meta-analysis reveals an association of PTPN22 C1858T with autoimmune diseases, which depends on the localization of the affected tissue

A B cell explanation for autoimmune disease: the forbidden clone returns

Contact Info

Product

Resources

About