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A study of antigen-specific anti-cytomegalovirus antibody reactivity in patients with systemic sclerosis and concomitant anti-Ro52 antibodies

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Abstract

Anti-Ro52 autoantibody (autoAb), highly prevalent in Sjogren’s syndrome (SjS) and systemic lupus erythematosus (SLE), is also frequent in systemic sclerosis (SSc). Viral agents, such as human cytomegalovirus (HCMV), have been considered as a trigger for SSc and SSc-associated autoAbs. To seek for antigen-specific anti-HCMV associations with anti-Ro52, we assessed the dominant anti-HCMV ab responses in anti-Ro52 antibody (ab)-positive and -negative patients with SSc and compared them with those in SLE and SjS. 116 Anti-HCMV ab(+) sera were analyzed, including 70 from anti-Ro52(+) patients (29 SSc, 23 SLE and 18 SjS) and 46 from anti-Ro52(−) patients (29 with SSc, 9 with SLE and 8 with SjS) as negative controls. Abs against specific HCMV pp130/UL57, pp65/UL83, pp55/UL55, pp52/UL44, p38 and pp28/UL99 antigens were tested by immunoblotting. Anti-Ro52(+) SSc patients reacted more frequently against pp52/UL44 and p38 compared to anti-Ro52(−) [(13/29, 44.8%; 95% CI 26.7–62.9% vs. 1/29, 3.4%; 95% CI 0–10%, p < 0.001, and 9/29, 31.0%; 95% CI 14.2–47.8% vs. 2/29, 6.9%; 95% CI 0–16.1%, p = 0.041, respectively]. No such differences were noted between anti-Ro52(+) and anti-Ro52(−) SLE or SjS patients. Also, antibody titres against HCMV pp65/UL83, pp52/UL44 and p38 antigens were higher in anti-Ro52(+) than anti-Ro52(−) SSc patients (p < 0.01). Ab responses against specific HCMV antigens differ among anti-Ro52 ab-positive and -negative patients with SSc (as well as between SSc and SLE or SjS), but whether these differences are epiphenomenal remains to be seen.

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Abbreviations

ab:

Antibody

autoAb:

Autoantibody

CEN:

Centromere

dcSSc:

Diffuse cutaneous systemic sclerosis

lcSSc:

Limited cutaneous systemic sclerosis

RNA pol III:

RNA polymerase III

Scl-70:

Scleroderma 70

SSc:

Systemic sclerosis

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Acknowledgements

We thank Dr. Gary L. Norman, Inova Diagnostics for providing anti-Ro52 antibody ELISA kits for free. Part of this work entitled “Is human cytomegalovirus a viral trigger of anti-Ro52 antibodies in patients with systemic sclerosis and systemic lupus erythematosus?” was presented as an oral presentation (Parallel session: Infection and Autoimmunity(OP 731) in the 11th International Congress of Autoimmunity, 16–20 May, Lisbon 2018.

Funding

This work was supported in part by the Special Fund for Research Grants (ELKE), Research Code: 2610 (2016–2021), University of Thessaly.

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Author notes

  1. Lazaros I. Sakkas and Dimitrios P. Bogdanos shared senior authorship.

Authors and Affiliations

  1. Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Βiopolis, 40500, Larissa, Thessaly, Greece

    Athanasios Gkoutzourelas, Christos Liaskos, Theodora Simopoulou, Christina Katsiari, George Efthymiou, Lazaros I. Sakkas & Dimitrios P. Bogdanos

  2. Institute of Immunology, Euroimmun, 23560, Lübeck, Germany

    Thomas Scheper, Wolfgang Meyer & Dimitrios P. Bogdanos

  3. Department of Immunology-Histocompatibility, Evangelismos General Hospital, Athens, Greece

    Alexandra Tsirogianni

  4. Laboratory of Microbiology, Democritus University of Thrace, Alexandroupolis, Greece

    Christina Tsigalou

  5. Department of Neurology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Βiopolis, 40500, Larissa, Greece

    Efthymios Dardiotis

  6. Division of Rheumatology, Department of Medicine, Patras University Hospital, Faculty of Medicine, University of Patras, 26504, Patras, Greece

    Dimitrios Daoussis

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  1. Athanasios Gkoutzourelas
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Contributions

AG and CL: Substantial contribution to acquisition of data, statistical analysis, drafting of significant parts of the work; TS and CK: Substantial contribution to acquisition of clinical data; GE, TS, ED, and WM: Substantial contribution to acquisition of data; AT and CT: Substantial contribution to acquisition of laboratory data and serum sampling; DD: Substantial contribution to acquisition of laboratory and clinical data and serum sampling; LIS: Drafting the work, revising it critically for important intellectual content and participating in study design; DPB: Original idea, study design, interpretation of data, supervision of experimental work, drafting of the work, revising it critically for important intellectual content. All authors approved the final version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Dimitrios P. Bogdanos.

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T. Scheper and W. Meyer are employees of Euroimmun; all other authors do not have anything to disclose.

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Gkoutzourelas, A., Liaskos, C., Simopoulou, T. et al. A study of antigen-specific anti-cytomegalovirus antibody reactivity in patients with systemic sclerosis and concomitant anti-Ro52 antibodies. Rheumatol Int 40, 1689–1699 (2020). https://doi.org/10.1007/s00296-020-04643-z

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