系统性红斑狼疮患者中输血传播病毒的患病率增加以及与HRES-1/p28内源性逆转录病毒自身抗原免疫显性表位的交叉反应性。

Increased prevalence of transfusion-transmitted virus and cross-reactivity with immunodominant epitopes of the HRES-1/p28 endogenous retroviral autoantigen in patients with systemic lupus erythematosus.

作者信息

Gergely Peter, Pullmann Rudolf, Stancato Christina, Otvos Laszlo, Koncz Agnes, Blazsek Antal, Poor Gyula, Brown Kevin E, Phillips Paul E, Perl Andras

机构信息

Section of Rheumatology, Department of Medicine, State University of New York, Upstate Medical University, College of Medicine, Syracuse, NY 13210, USA.

出版信息

Clin Immunol. 2005 Aug;116(2):124-34. doi: 10.1016/j.clim.2005.04.002.

DOI:10.1016/j.clim.2005.04.002

PMID:15894513

Abstract

OBJECTIVE

Systemic lupus erythematosus (SLE) patients produce autoantibodies to HRES-1/p28, a human endogenous retrovirus-encoded nuclear protein. To identify cross-reactive viral antigens capable of triggering autoreactivity, HRES-1/p28 epitopes were mapped by SLE antibodies.

METHODS

Forty-four peptides overlapping HRES-1/p28 and 13 viral peptides were synthesized on cellulose membrane and tested for recognition by antibodies from 16 HRES-1 Western blot seropositive SLE patients. Transfusion-transmitted virus (TTV) was detected by gene amplification in sera of 211 SLE patients, 78 healthy SLE family members, 199 unrelated healthy donors, and 91 rheumatoid arthritis (RA) patients.

RESULTS

HRES-1/p28 residues 41-55, 121-135, and 156-170 were recognized by 12/16 (75.0%), 11/16 (68.8%), and 9/16 lupus sera (56.25%) and considered immunodominant. HRES-1/p28 residues 121-135 harbor cross-reactive epitope with retroviral peptides and the 70 K U1snRNP lupus autoantigen. HRES-1/p28 residues 41-55 and 156-170 exhibited the highest prevalence of cross-reactivity with TTV peptide ORF2a (14/16, 87%). Prevalence of TTV DNA was increased in lupus patients (120/211) with respect to healthy (66/199; P < 0.0001) or RA controls (23/91; P < 0.0001). TTV prevalence in healthy lupus relatives (40/78) was decreased with respect to lupus patients (80/121; P = 0.0184) and increased with respect to unrelated healthy donors (66/199; P = 0.0026). HRES-1/p28 Western blot reactivity was observed in 12/23 TTV PCR-negative donors and 43/58 TTV PCR-positive donors (P < 0.0281).

CONCLUSIONS

Increased prevalence of TTV and molecular mimicry with HRES-1/p28 may contribute to generation of antinuclear antibodies and pathogenesis of SLE.

摘要

目的

系统性红斑狼疮（SLE）患者会产生针对HRES-1/p28的自身抗体，HRES-1/p28是一种人类内源性逆转录病毒编码的核蛋白。为了鉴定能够引发自身反应性的交叉反应性病毒抗原，通过SLE抗体对HRES-1/p28表位进行了定位。

方法

在纤维素膜上合成了44个与HRES-1/p28重叠的肽段和13个病毒肽段，并检测了16例HRES-1免疫印迹血清学阳性的SLE患者血清中的抗体对其的识别情况。通过基因扩增检测了211例SLE患者、78例健康的SLE家庭成员、199例无关健康供者以及91例类风湿关节炎（RA）患者血清中的输血传播病毒（TTV）。

结果

HRES-1/p28的41-55位氨基酸残基、121-135位氨基酸残基和156-170位氨基酸残基分别被12/16（75.0%）、11/16（68.8%）和9/16（56.25%）的狼疮血清识别，被认为是免疫显性表位。HRES-1/p28的121-135位氨基酸残基与逆转录病毒肽段和70K U1snRNP狼疮自身抗原有交叉反应性表位。HRES-1/p28的41-55位氨基酸残基和156-170位氨基酸残基与TTV肽段ORF2a的交叉反应性发生率最高（14/16，87%）。与健康对照（66/199；P<0.0001）或RA对照（23/91；P<0.0001）相比，狼疮患者（120/211）中TTV DNA的发生率升高。与狼疮患者（80/121；P=0.0184）相比，健康狼疮亲属（40/78）中TTV的发生率降低，与无关健康供者（66/199；P=0.0026）相比则升高。在23例TTV PCR阴性供者中有12例以及58例TTV PCR阳性供者中有43例观察到HRES-1/p28免疫印迹反应性（P<0.0281）。