Induction of Antiphospholipid Autoantibody During Cytomegalovirus Infection

Cheng, Hwee Ming; Khairullah, Nor Shahidah

doi:10.1086/517010

Cited by 24 publications

(8 citation statements)

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“…A higher prevalence of an autoantibody to the U1 snRNP in SLE patients, as well as in animals, has been reported [11,12]. There are also other studies that reported that an HCMV infection induced the Ro60 antigen expression on the cell surface and elevated the antiphospholipid antibody [23,24]. So, HCMV antigens that mimic autoantigens may be responsible for the immunological abnormalities of SLE patients.…”

Section: Discussionmentioning

confidence: 89%

Correlation between systemic lupus erythematosus and cytomegalovirus infection detected by different methods

et al. 2015

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Human cytomegalovirus (HCMV), a β-herpes virus subfamily member, leads to a lifelong, latent infection in most humans, but the correlation between HCMV infection and systemic lupus erythematosus (SLE) remains controversial. We analyzed the relevance of HCMV infection in SLE by analyzing the peripheral blood leukocytes (PBLs) and serum samples of 60 patients with SLE and 111 healthy individuals. HCMV genes UL55 and UL138 were detected in PBLs by polymerase chain reaction (PCR), and HCMV-specific serum IgG and IgM antibodies were investigated by enzyme-linked immunosorbent assay. The relationship between cellular HCMV infection in PBLs and common clinical indicators of SLE was further explored. Data indicated that the frequency of positive IgG and IgM anti-CMV antibodies was not significantly different in SLE patients and controls. However, compared to the healthy controls, the titers of IgG and IgM anti-CMV antibodies in SLE patients were significantly higher. The detection of cellular HCMV infection showed that almost all subjects were positive for UL138 gene in PBLs, but the positivity for UL55 gene was lower in PBLs. HCMV UL138 detection in PBLs was highly consistent with the frequency of the HCMV-specific IgG test and did not show significant difference in SLE patients and healthy controls. However, compared with that in healthy people, the positivity rate for cellular HCMV UL55 detection was significantly higher in SLE patients (P < 0.001). In addition, cellular HCMV UL55 with positive detection in PBLs was associated with significantly different clinical characteristics of SLE than that with negative detection. In conclusion, our data confirmed that the HCMV infection was related to the development of SLE. Especially, some clinical strains or substrains of HCMV, such as containing the UL55 gene in HCMV's genome, might play a vital role in the development of SLE.

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Section: Discussionmentioning

confidence: 89%

Correlation between systemic lupus erythematosus and cytomegalovirus infection detected by different methods

et al. 2015

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“…Specific activation of both viral-specific and auto-reactive T-cells during infection has been shown to accelerate the development of type I diabetes [5,6]. HCMV-infection-induced Ro60 antigen expression on the cell surface and elevated anti-phospholipid antibody has been reported [7,8]. In addition, a higher prevalence of autoantibody to U1 small nuclear ribonucleoprotein (U1 snRNP) in SLE patients and animals are associated with HCMV infection or immunization, respectively [9,10].…”

Section: Introductionmentioning

confidence: 99%

Fragment of tegument protein pp65 of human cytomegalovirus induces autoantibodies in BALB/c mice

Hsieh

Jhou

Liang³

et al. 2011

Arthritis Res Ther

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IntroductionHuman cytomegalovirus (HCMV) infection has been implicated in the development of autoimmunity, including systemic lupus erythematosus (SLE). Previously we reported that HCMV phosphoprotein 65 (pp65) could induce early onset of autoantibody and glomerulonephritis on lupus-prone NZB/W mice. This study further examined whether the B cell epitope(s) in pp65 is able to drive the development of autoantibody.MethodsSera from SLE patients or HCMVpp65-immunized mice were analyzed for anti-nuclear antibody by immunoblotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescent stain and Crithidia luciliae stain. The deposition of immunoglobulin to the kidney was also examined by immunofluorescent stain. The interactions between pp65 sub-fragment to cellular proteins were revealed by yeast two-hybrid analyses.ResultsOur results showed that most SLE patients possessed antibodies to the C-terminal half of the HCMVpp65 antigen. Of these positive sera, 73% were also positive to the pp65336-439 sub-fragment. The immunization of pp65336-439 induced formation of multiple anti-nuclear antibodies, including anti-chromatin, anti-centriole, anti-mitotic spindle type I/II (MSA I/II) and a significant elevation of anti-double-stranded DNA (anti-dsDNA) antibodies on BALB/c mice. Yeast two-hybrid analyses revealed the binding of pp65336-439 sub-fragment to cellular proteins. Immunoglobulin deposition on glomeruli was also detected on pp65336-439-immunized mice.ConclusionsOur data suggested that HCMVpp65336-439 sub-fragment may induce cross-reactive antibodies to several nuclear antigens, which could contribute to the development of autoimmunity in genetic-suspected individuals.

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“…syphilis (9), Q fever (10), lyme disease (11), mycoplasma (12), tuberculosis (13), leprosy (14), etc. Furthermore, aPL antibodies have also been reported in viral infections: HIV (15), cytomegalovirus (16), varicella zoster virus (17), hepatitis C (18), and Epstein-Barr (19).…”

Section: Introductionmentioning

confidence: 99%

Prevalence of antiphospholipid and antiplatelet antibodies in human immunodeficiency virus (HIV)‐infected Chilean patients

Palomo

Alarcón

Sepúlveda

et al. 2003

Clinical Laboratory Analysis

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Antiphospholipid (aPL) and antiplatelet (aPlt) antibodies, found in patients with autoimmune diseases, are also detected in infectious diseases. The purpose of this study was to examine the prevalence of these antibodies in HIV patients and to evaluate an association of these antibodies with thrombocytopenia and/or thrombosis. Sixty-three HIV-seropositive patients and 52 normal controls were studied. Anti-cardiolipin (aCL), anti-beta(2) glycoprotein I (anti-beta(2)GPI), and antiprothrombin (aPT) antibodies were determined and the lupus anticoagulant (LA) test was performed. Antiplatelet antibodies (aPlt) were also determined. Seven out of 63 (12.7%) HIV patients were positive for aCL, four of 63 (6.3%) for anti-beta(2)GPI, and five of 63 (7.9%) for aPT. No patients studied were LA positive. Six out of 63 (9.5%) patients were positive for aPlt. One of them showed weak reactivity for GPIb-IX. The platelet count of patients (202+/-63 x 10(3) platelets/microL) was significantly lower than in the controls (343+/-6 x 10(3) platelets/microL) (P<0.001). There was no correlation between the presence of aPL and/or aPlt and thrombocytopenia. Of the HIV-infected patients, 22.2% presented aPL and 9.4% aPlt antibodies. In this study, the presence of aPL and aPlt antibodies was not associated with the development of thrombosis and/or thrombocytopenia.

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Induction of Antiphospholipid Autoantibody During Cytomegalovirus Infection

Cited by 24 publications

References 3 publications

Correlation between systemic lupus erythematosus and cytomegalovirus infection detected by different methods

Correlation between systemic lupus erythematosus and cytomegalovirus infection detected by different methods

Fragment of tegument protein pp65 of human cytomegalovirus induces autoantibodies in BALB/c mice

Prevalence of antiphospholipid and antiplatelet antibodies in human immunodeficiency virus (HIV)‐infected Chilean patients

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