A Study on the Association of HLA-DR Alleles,gene sequence and patients with Systemic Lupus Erythematosus in Chinese Children


LI Caifeng  HE Xiaohu JIANG Zaifang  et al


Objective:   To study the correlation between HLA- DR alleles and systemic lupus erythematosus(SLE) in Chinese children and to find the influence of HLA gene with clinical phenomenon by sequence analysis.Methods:   HLA- DR alleles were tested in 53 patients with SLE (lupus nephritis 15, lupus encephalopathy 7, lupus nephritis and lupus encephalopathy 10, and 21 without either lupus nephritis or lupus encephalopathy) and 78 normal controls by Polymerase Chain Reaction - Sequence Specific Primers (PCR-SSP).The gene sequence of HLA-DRB1*15 in 35 cases of SLE with HLA-DRB1*15 was tested by Polymerase Chain Reaction - Single Strand Conformational Polymorphism(PCR-SSCP) and PCR productions sequencing to discover gene mutation.


Results:   The frequency of HLA-DRB1*15, DRB1*03 in SLE group was much higher than that in control group with significant statistical difference (PC0.05), the RR were 4.5238 and 5.4146 respectively. The frequency of HLA-DRB1*04 in SLE group was much lower than that in control group with significant statistical difference (PC0.05). Clinical date showed that patients with DRB1*03 much more easily complicated with lupus nephritis, whereas the patients with DRB1*15 had all kinds of the clinical manifestations.The sequence analysis results showed that 6 cases had C→G replacement mutation in 123th nucleotide resulting in D→E replacement (aspartic acid to glutamic acid) in 41th amino acid. Clinical data showed that 4/6 cases with mutation had both lupus nephritis and CNS lupus, whereas 4/29 cases without mutation didnt complicate with either lupus nephritis or lupus encephalopathy. Conclusion:  These findings suggested that HLA-DRB1*15, HLA-DRB1*03 were susceptible genes in SLE, and HLA-DRB1*04 was protective gene. DRB1*03 mainly associated with lupus nephritis and DRB1*15 was associated with all kind of clinical types. HLA-DRB1*15 gene mutation and replacement of amino acid were correlated with the severity of SLE. We presumed that the clinical phenotypes of severe patients might be due to the replacement of amino acid, which might result in changes of the construction of HLA molecule and influence their functions.We inferred that the HLA structural changes might influence the clinical types.


[Key Words]  SLE; HLA Alleles; Predisposing Gene;Gene Mutation