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Letter

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

Gn Kim and Think-You Kim*

Author affiliations

Department of Early Arthritis/Laboratory of Medicine, The Hospital for Rheumatic Diseases, Hanyang University Medical Center, 133-792 Seoul, Republic of Korea

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Citation and License

Arthritis Research & Therapy 2012, 14:404  doi:10.1186/ar4023


See related research by Hsieh et al., http://arthritis-research.com/content/13/5/R162

The electronic version of this article is the complete one and can be found online at: http://arthritis-research.com/content/14/5/404


Published:10 September 2012

© 2012 BioMed Central Ltd

Letter

We read with interest the recent paper by Hsieh and colleagues [1] asserting that cytomegalovirus (CMV) induces systemic lupus erythematosus (SLE) in genetically susceptible individuals. This assertion is based on the idea that SLE-associated autoantibodies that had been induced by a certain fragment of CMV were found in rodents. However, our previous studies have reported that autoantibodies detected in SLE and viral infection are different, especially with regard to the anti-microtubule organizing center with microtubule (anti-MTOC-MT) [2-4]. We conducted a retrospective study comparing autoantibodies in three groups: anti-CMV IgM-positive SLE patients (SLE-CMV group); anti-CMV IgM-positive patients without SLE (CMV group); and anti-CMV IgM-negative SLE patients (SLE group). This study was approved by the institutional review board of Hanyang University Medical Center.

Autoantibodies from 245 patients were analyzed from January 2005 to March 2012 by the autoimmune target (AIT) test, which was developed to overcome the limitations of the antinuclear antibody test using the human macrophage cell line (IT-1) as a substrate [2].

What is noteworthy is that anti-MOTC-MT was highly detected in the CMV group, while it was not detected in all SLE patients regardless of CMV infection. Moreover, if CMV is a cause of SLE, detected autoantibodies between the SLE-CMV and CMV groups should overlap, but they show a clear distinction (Table 1).

Table 1. Immunofluorescence patterns and titers of AIT test in SLE-CMV, SLE and CMV groups

CMV becomes latent in multiple organs and can later be reactivated during severe dysregulation of the immune system. In our study, over 90% of patients in the three groups were anti-CMV IgG-positive. Detection of anti-CMV IgG implies the presence of latent virus, but anti-CMV IgG does not protect the individual from reactivation of the latent virus. In contrast, anti-CMV IgM responses are often seen during reactivation of CMV, so it seems that CMV infection in the SLE-CMV group was not caused by primary infection but by reactivation of CMV. MTOC, cytokines and T cells are closely coordinated to maintain the immune system [5] and anti-MTOC-MT is not found in SLE patients owing to impairment of the immune system. In conclusion, we postulate that CMV is not sufficiently intense to cause SLE, but is reactivated in some SLE patients as an innocent bystander.

Abbreviations

AIT: autoimmune target; CMV: cytomegalovirus; MTOC-MT: microtubule organizing center with microtubule; SLE: systemic lupus erythematosus.

Competing interests

Think-You Kim holds patents relating to the IT-1 cell line.

References

  1. Hsieh AH, Jhou YJ, Liang CT, Chang M, Wang SL: Fragment of tegument protein pp65 of human cytomegalovirus induces autoantibodies in BALB/c mice.

    Arthritis Res Ther 2011, 13:R162. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text OpenURL

  2. Jearn LH, Kim DA, Kim TY: Limitations of antinuclear antibody tests (HEp-2) are overcome with the autoimmune target test (IT-1) in systemic lupus erythematosus.

    J Rheumatol 2009, 36:1833-1834. PubMed Abstract | Publisher Full Text OpenURL

  3. Sir JU, Kim TY: MTOC-MT is a major target antigen of autoantibody detected by autoimmune target tests in patients with hepatitis A virus infection.

    J Clin Pathol 2010, 63:1129. PubMed Abstract | Publisher Full Text OpenURL

  4. Sir JU, Kim TY: Autoantibodies are commonly detected by the AIT test in patients with chronic hepatitis C virus infection.

    J Viral Hepat 2010, 17:379. PubMed Abstract | Publisher Full Text OpenURL

  5. Martín-Cófreces NB, Robles-Valero J, Cabrero JR, Mittelbrunn M, Gordón-Alonso M, Sung CH, Alarcón B, Vázquez J, Sánchez-Madrid F: MTOC translocation modulates IS formation and controls sustained T cell signaling.

    J Cell Biol 2008, 182:951-62. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL