The analysis of PRF1 STX11 UNC13D STXBP2 gene and clinical features in macrophage activation syndrome associated with systemic juvenile idiopathic arthritis / 中华风湿病学杂志

ABSTRACT

Objective To investigate the clinical characteristics of 34 systemic onset juvenile idiopathic arthritis (SoJIA) complicated with macrophage activation syndrome (MAS) and analyzed the gene PRF1,UNC13D,STX11,STXBP2 to figure out the genetic pathogenesis mechanism.Methods The clinical characteristics of 34 SoJIA complicated with MAS were analyzed retrospectively and coding sequences of PRF1,UNC13D,STX11 were amplified and tested.The Chi-square test was applied to compare the distribution of alleles and genotypes frequencies between SLE patients and healthy controls.Statistical significance was defined as P value ＜0.05.Results A total number of 34 SoJIA complicated with MAS were included.Boys accounted for 69％(23/34),and the median age was 6 years.85％(29/34) cases had genetic tests and four SNPS loci were detectedPRF1 c.1061 C＞T (rs885822); UNC13D c.659 C＞T (rs3744007); STXBP2 c.1483 T＞cC (rs10001) and STXBP2 c.1616 A＞G (rs6791).Compared with the control group,genotype and allele frequency of PRF1 rs885822 and STXBP2 rs10001 in MAS cases were statistical significantly different (rs885822allele frequency x2=4.52,P=0.03 ; genotype frequencyx2=5.52,P=0.02.rs10001allele frequencyx2=21.33,P=0.00; genotype frequencyx2=19.58,P=0.00).There was no statistical significant difference in genotype frequency and allele frequency of UNC13D rs3744007 and STXBP2 rs6791 between the MAS and control group (rs3744007allele frequencyx2=1.89,P=0.17; genotype frequencyx2=1.59,P=0.45.rs6791allele frequency x2=l.69,P=0.19; genotype frequencyx2=2.09,P=0.35).Persistent fever,progressive hepatos-plenomegaly,a sharp decline in blood cells counts,pleural effusion,markedly increased serum liver enzymes,hyperlipidemia were the main characteristics.Some children had mucosal bleeding,neurological dysfunction.More than 82％ children had upper respiratory tract infection before the occurrence of MAS.90％ of children were in remission,while three children had multiple organ failure and died.Conclusion MAS is a fatal complication caused by immune disturbance.Early detection and tre-atment is the key to improve the prognosis.The SNP PRF1 rs885822 and STXBP2 rs1001 may be concurrent with the pathogenesis of SoJIA-MAS.The SNP UNC13D rs3744007 and STXBP2 rs6791 may not participate in the pathogenesis of SoJIA-MAS.