TLR-2 Arg753Gln, TLR-4 Asp299Gly, and TLR-4 Thr399Ile polymorphisms in Henoch Schonlein purpura with and without renal involvement

Abstract

Infections may trigger or aggravate glomerulonephritidis and renal vasculitis like Henoch Schonlein purpura (HSP). HSP is seen more frequently in patients with familial Mediterranean fever in which TLR-2 Arg753Gln polymorphism frequency is increased. Although renal involvement is the most important factor affecting the prognosis in HSP, it is not known which patients will have renal disease or why some patients have severe renal involvement while some others have mild renal disease. We investigated the role of TLR-2 and TLR-4 polymorphisms on the incidence and severity of renal involvement in HSP patients. We studied HSP patients with and without nephritis (n = 15 for each group) and healthy controls (n = 100). TLR-2 Arg753Gln and TLR-4 Asp299Gly/Thr399Ile polymorphisms were analyzed with polymerase chain reaction-restriction fragment length polymorphism method. The frequency of TLR-2 Arg753Gln, TLR-4 Asp299Gly, and Thr399Ile polymorphisms in healthy controls were 1, 3, and 2%, respectively. The frequencies of these polymorphisms were not different in HSP patients with or without nephritis compared to healthy controls. TLR-2 Arg753Gln, TLR-4 Asp299Gly, and Thr399Ile polymorphisms are not increased in HSP or HSP nephritis patients.

TLR Polymorphisms in FMF: Association of TLR-2 (Arg753Gln) and TLR-4 (Asp299Gly, Thre399Ile) Polymorphisms and Myeloid Cell TLR-2 and TLR-4 Expression with the Development of Secondary Amyloidosis in FMF

“…The frequency of these polymorphisms is around 2.6% to 10% in healthy controls in Western populations [26,27]. The frequency among our controls in the previous study was 3% for Asp299Gly and 2% for Thr399Ile polymorphisms [18], being compatible with the rates reported in a healthy Turkish population previously (2.9% and 2.3%, respectively) [28]. The frequency among the study population (one in all 39 FMF patients, 2.6%) was not increased contrary to our expectation.…”

“…In fact, none of the 26 patients without amyloidosis had these polymorphisms, albeit we assumed this group of patients to have higher rates of polymorphisms than both those with a Time between the onset of symptoms and the onset of colchicine treatment b Patients with phenotype 1 (n=6) were considered for this analysis c Presence of M694V allele in patients with vs without amyloidosis d All patients with amyloidosis were given colchicine only after they had amyloidosis associated nephrotic syndrome e Excluding patients with end-stage renal disease Table 2. TLR-2 Arg753Gln, TLR-4 Asp299Gly, and TLR-4 Thre399Ile Polymorphisms TLR-2 Arg753Gln a n (%) TLR-4 Asp299Gly a n (%) TLR-4 Thre399Ile a n (%) a There is no significant difference between the groups b Healthy controls enrolled in our previous study (reference 18) amyloidosis and the controls. Although our study population is small, these results suggest that TLR-4 Asp299Gly and Thr399Ile polymorphisms do not have a modifying role on the course of FMF as described for the TLR-2…”

“…Among 100 healthy controls, one (1.0%) had TLR-2 Arg753Gln, three (3.0%) TLR-4 Asp299Gly, and two (2%) TLR-4 Thr399Ile polymorphisms [18]. None of the FMF patients had the TLR-2 Arg753Gln polymorphism.…”

“…The control group consisted of 100 healthy cases used in our previous study [18]. In addition, 13 new control cases were included to be evaluated for TLR-2 and TLR-4 expressions and for SAA level measurement.…”

Toll-Like Receptor 2–Blocking Antibodies Promote Angiogenesis and Induce ERK1/2 and AKT Signaling via CXCR4 in Endothelial Cells

“…6 The resulting complications are associated with various vascular diseases linked to inflammation and autoimmunity, such as atherosclerosis, 7 ischemia and reperfusion injury, 8 and vasculitis. 9 In contrast, TLR2 deficiency seems to preserve endothelial cell function during vascular inflammatory processes. 10 For example, murine TLR2 knockout was associated with protection of atherosclerosissusceptible low-density lipoprotein receptor-deficient mice from lesion progression, 11 contained ischemia and reperfusioninduced damage to tissues, 8 reduced coronary endothelial dysfunction, and smaller infarct size after myocardial infarction.…”