Evidence for Human Leukocyte Antigen-Related Susceptibility in Idiopathic Childhood Ischemic Stroke

Abstract

Stroke in children is a relatively uncommon condition and frequently associated with other diseases like cardiopathies, sickle cell disease and chronic smoking. In contrast to stroke in adults, it is rarely caused by atherosclerosis, hypertension or diabetes mellitus. Childhood stroke of unknown causes is called idiopathic stroke. The etiology of idiopathic stroke is unknown. However, several so-called idiopathic diseases develop on the basis of a genetic predisposition. As an approach to investigate this possibility in idiopathic childhood ischemic stroke, we studied the relationship between clinical and immunogenetic features in this disease. We demonstrate that the gene frequencies and relative risk of HLA-B51 were markedly increased in our patients compared with controls (p < 0.001). Thirteen of seventeen HLA-B51-positive patients had had a preceding respiratory infection, which was a higher proportion than in the control group (p < 0.05). In the patient group, the alleles HLA-DRB1*0802, -DRAI*0401 and -DQBI*0402 were also significantly increased, defining the haplotype DRB1*0802-DRA1*0401-DQB1*0402 as a high-risk haplotype for idiopathic childhood ischemic stroke. Transient viral or bacterial infections, which involve vasculitis and vascular occlusion in the brain, can trigger idiopathic childhood ischemic stroke on the basis of an genetic predisposition.

The association of CTLA‐4 and CD28 gene polymorphisms with idiopathic ischemic stroke in the paediatric population

“…Though the aetiology of idiopathic childhood ischemic stroke remains largely unknown, HLA‐B51 is believed to be the strongest indicator for the disease in the different ethnic populations which include those from China (Mintz et al ., 1992; Zou et al ., 2002). Likewise, our previous study showed a high prevalence of the HLA‐DRB1*0802‐DRA1*0401‐DRB1*0402 haplotype in children who suffered idiopathic ischemic stroke (Zou et al ., 2002). According to these findings, idiopathic ischemic stroke can be considered as a multigene autoimmune disorder.…”

“…idiopathic thrombocytopenic purpura, non‐specific interstitial pneumonia and inflammatory myopathy (Kim & Nagai, 2007; Mimori et al ., 2007), may partly involve autoimmune processes. Our previous study showed that autoimmune vasculitis resulting from the T‐cell activation might be an important point of study in the development of the idiopathic ischemic stroke in children (Zou et al ., 2002). Thus, the variants of the genes that regulate the activation and proliferation of the T cells may influence the risk of childhood stroke.…”

“…Our previous study indicated that antigen presentation might be involved in triggering the initiation and activation of idiopathic ischemic stroke in children (Zou et al ., 2002). Molecules involved in co‐stimulation of T‐cell activation may be important in the regulation of antigen presentation in idiopathic stroke.…”

Arterial Ischemic Stroke in Neonates and Children: Review and Current Issues

“…Congenital vascular malformations may accompany recognizable syndromes, such as PHACES (posterior fossa malformations, hemangiomas, arterial anomalies, coarctation, eye anomalies, sternal pit) [86] or occur sporadically and predispose to AIS [87]. Research has also begun to explore the effect of multiple genetic polymorphisms on stroke risk in children with other risk factors such as SCD [88] and infectious vasculitis [89]. Epidemiological studies have shown that both male gender and black skin color are associated with a higher risk for AIS in childhood [90].…”

HLA-DRB1 alleles in Hb SS patients with avascular necrosis of the femoral head

“…In spite of this uniform genotype, there is phenotypic heterogeneity and the associated factors (environmental or genetic) are still to be elucidated. Several studies have shown that immunogenetics, especially HLA types, play a significant role in SCD [11][12][13][14], just as they do in other vascular diseases characterized by blood cellular interactions with the endothelium [15][16][17] [12,14]. We are, however, not aware of any previous studies of HLA allele association studies with AVN in SCD.…”