IRAK2 is associated with systemic lupus erythematosus risk.

INTRODUCTION: Interleukin-1 receptor-associated kinases (IRAKs) are serine-threonine kinases involved in toll-like receptor and interleukin-1 signaling pathways. They play a key role in inflammation and innate immunity. IRAKs have been previously incriminated in autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis and inhibition of IRAKs has been recently regarded as a potential therapeutic strategy for SLE. OBJECTIVES: The aim of the present study was to test the association between IRAK2 rs708035 and rs3844283 with SLE. MATERIAL AND METHODS: IRAK2 rs708035 and rs3844283 were genotyped by mutagenically separated polymerase chain reaction (MS-PCR) in 142 SLE patients and 149 age- and gender-matched controls. RESULTS: The hyperfunctional IRAK2 rs708035 A allele was more frequent among SLE patients than controls (62.9% versus 54.7%, p = 0.046). IRAK2 rs3844283 C allele was present in 66.5% of patients and 75.5% of controls. The CC genotype was the most frequently exhibited genotype. It was carried by 45.1% of patients with SLE and 57.7% of controls. The G allele was associated with an increased risk of SLE (OR = 1.54, 95%, CI = 1.07-2.22, p = 0.017). IRAK2 rs708035 and IRAK2 rs3844283 were in linkage disequilibrium (D' = 0.64). The AG haplotype was more frequently observed in SLE patients than in controls (0.292 versus 0.194, p = 0.008). CONCLUSION: This study for the first time ever reveals the association of IRAK2 rs708035 and IRAK2 rs3844283 and the corresponding haplotypes with SLE. Our findings give additional rationale to target IRAKs in the treatment of SLE.Key Points• IRAK2 rs708035 A allele is more frequent in SLE patients than in controls and IRAK2 rs3844283 G allele is associated with SLE susceptibility.• These two alleles are in linkage disequilibrium.• The AG haplotype is associated with SLE.

The role of enterovirus infections in type 1 diabetes in Tunisia.

BACKGROUND: Enteroviral infections have long been suspected in having a role in ß cell destruction and therefore leading to the onset of clinical type 1 diabetes (T1D). The frequency of enterovirus (EV)-related T1D in North Africa is still unknown. The aim of the present study was to investigate the relationship between infection with EV and T1D in Tunisia. METHODS: A total of 95 T1D patients (41 children and 54 adults) and 141 healthy control subjects (57 children and 84 adults) were tested for the presence of EV-RNA by a highly sensitive nested reverse transcription-polymerase chain reaction (RT-PCR) method. RESULTS: EV-RNA was detected more frequently in plasma from diabetic patients than in plasma of controls (31.6% vs. 7.8%, p<0.0001; OR=5.45; 95% CI 2.44-12.43). RT-PCR revealed positive in 53.7% of T1D children and 14.8% of T1D adults. There was a statistically significant difference between children and adults with T1D (p<0.0001). Positivity of EV-RNA according to the time after the occurrence of the disease did not show any significant difference (p=0.34). Anti-glutamic acid decarboxylase (GAD) antibodies were not associated with EV-RNA (p=0.65). CONCLUSIONS: EV-RNA is associated with T1D mellitus in the Tunisian population especially in children. These results support the hypothesis that EV act as environmental risk factors for T1D.

[Catastrophic antiphospholipid syndrome. Report of two cases]. / Syndrome catastrophique des antiphospholipides. A propos de deux observations.

The antiphospholopid syndrome has been associated with thromboembolic events, thrombocytopenia and fetal loss. Some patients with the antiphospholipid syndrome may develop an acutely catastrophic syndrome characterized by multiple vascular occlusions which often results in death. Most patients dye as a result of a combination of cardiac and pulmonary failure. Although trigger factors are present in a minority, in the majority the condition develops quite suddenly. Precipitating factors include infections and trauma (surgical). Treatment of the condition, once recognized, needs to be heroic. Plasmapheresis seems to be useful in several cases who had not responded to conventional therapy (heparin, steroids, immunosuppressive) directed against immunologically mediated intravascular thrombosis. We report here two cases of fatal catastrophic antiphospholipid syndrome and highlight the need for vigilance in the management of patients with antiphospholipid syndrome.