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Response to 'Fragment of tegument protein pp65 of human cytomegalovirus induces autoantibodies in BALB/c mice'
Arthritis Research & Therapy volume 14, Article number: 404 (2012)
We read with interest the recent paper by Hsieh and colleagues  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 .
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).
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  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.
microtubule organizing center with microtubule
systemic lupus erythematosus.
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: R162-10.1186/ar3481.
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.
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-
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: 379-10.1111/j.1365-2893.2009.01202.x.
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. 10.1083/jcb.200801014.
Think-You Kim holds patents relating to the IT-1 cell line.
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Kim, G., Kim, T. Response to 'Fragment of tegument protein pp65 of human cytomegalovirus induces autoantibodies in BALB/c mice' . Arthritis Res Ther 14, 404 (2012). https://doi.org/10.1186/ar4023
- Systemic Lupus Erythematosus
- Systemic Lupus Erythematosus Patient
- Latent Virus
- Tegument Protein
- Innocent Bystander