Relationship Between Sero-resistance And Molecular Subtypes Of Treponema Pallidum Repeat Gene

IntroductionSyphilis is a sexually transmitted disease caused by the bacterium treponema pallidum. It spreads mainly by sexual contact, but may also be transmitted by infected mothers to their unborn children. It has become widely popular and spread around the world that continues to be a serious public health problem. The incidence of syphilis ascends gradually in China in recent years, and it is an important threat to people's health and social stability. In addition to skin and mucous membranes, syphilis may affect bones and joints, eyes, central nervous and cardiovascular system, that can be very serious or even fatal. An infected mother can pass syphilis through the placenta to her developing fetus, which can lead to stillbirth, premature birth or neonatal congenital syphilis, endanger the health of the next generation. Syphilis is a sexually transmitted genital ulcer disease, and it increases susceptibility to human immunodeficiency virus (HIV). The mode of transmission and predisposing factors between syphilis and acquired immune deficiency syndrome(AIDS) have a lot in common, It is generally believed that an increase incidence in syphilis increases the risk of HIV transmission. So early prevention and treatment of syphilis is the key of prevent and reduce the spread of AIDS.After being infected by syphilis,the body could produces two kinds of antibodies: the non-specific antibody and the specific treponema pallidum antibody, and the non-specific antibody is the key indicator of the therapeutic effect. After standard treatment of syphilis patients, most of them clinical symptoms disappeared and the serological test for syphilis may be negative. However,in clinical work,we have usually discover some patients with clinical symptoms completely disappeared after treatment,but the process of follow-up serological test is till positive for a long time,that is sero-resistance, which is a difficult problem to solve. A molecular typing system was developed and introduced by Pillay in the late 1990s.In recent years, many researchers focus on TP tpr gene, a study suggested that TP tpr gene family is the major virulence factor for syphilis, which is the main target gene of the host's humoral immune response, it may play an important role in the immune response in syphilis infection, some scholars find different types of TP tpr gene can lead to a different antibody response and immune response.There was no report about the relationship between sero-resistance and subtypes of TP tpr gene at present. To explore the distribution of subtypes of TP tpr gene in Guangzhou area and the relationship with sero-resistance at the molecular level by nested PCR, it may be helpful for elucidating the pathogenesis of syphilis, providing a theoretical basis for rational therapy, solving clinical problems, and it is also very important to reduce the spread of syphilis and AIDS.ObjectiveTo find out the distribution of subtypes of treponema pallidum repeat (tpr) gene in Guangzhou area and investigate the relationship between the sero-resistance and molecular subtypes of tpr gene, and to provide laboratory basis for syphilis prevention and its molecular epidemiological study. Methods102 specimens of confirmed patients with untreated early syphilis, including 75 specimens of whole blood and 27 specimens of ulcer secretions, were collected by number of hospitals in Guangzhou area. TP basic membrane protein (bmp) genes were screened from these specimens by nested PCR. The positive specimens were amplified with the primers of TP tpr gene. The amplified products were typed by restriction fragment length polymorphism (RFLP). The patients with early syphilis were followed up for 12 months and the serum titers of TRUST were tested. After standard treatment, the relationship between the change of serum TRUST titer of the patients and the subtypes of TP tpr gene were analyzed.ResultsTP DNA was found in 48 specimens of genital lesions secretions and whole blood, from 86 valid patients with primary syphilis. There was no statistical significance between initial TRUST titers and positive rate by the nested PCR by the bilateral Fisher's exact test(P=0.24). Forty of 48 had typeable DNA. Three molecular subtypes were found, including subtype d (28), e (4), and i (8). The serum titer of TRUST became negative in 33(33/40) patients 12 months after therapy, 7 patients occurred sero-resistance which include 3 subtype d and 4 subtype i. the incidence of Sero-resistance of subtype i is the highest.There were statistical differences between sero-resistance and molecular subtypes of tpr gene by the bilateral Fisher's exact test(P=0.04).ConclusionsTP tpr gene subtype d is the predominant strain in Guangzhou area, the results suggested that the sero-resistance may be related with TP tpr gene subtypes.