Only monospecific anti-DFS70 antibodies aid in the exclusion of antinuclear antibody associated rheumatic diseases: an Italian experience.


Journal

Clinical chemistry and laboratory medicine
ISSN: 1437-4331
Titre abrégé: Clin Chem Lab Med
Pays: Germany
ID NLM: 9806306

Informations de publication

Date de publication:
25 Oct 2019
Historique:
received: 30 04 2019
accepted: 18 06 2019
pubmed: 19 7 2019
medline: 18 9 2020
entrez: 19 7 2019
Statut: ppublish

Résumé

Background The dense fine speckled (DFS) is one of the most common patterns that can be observed as a result of the anti-nuclear antibodies (ANA) test on HEp-2 cells and is mostly caused by antibodies to DFS70 as the main antigenic target. As was recently demonstrated, isolated anti-DFS70 positivity can be used as an aid in the exclusion of ANA associated rheumatic diseases (AARD) due to the opportunity to better interpret unexplained positive IIF ANA results. Methods Our study included 333 subjects with AARD, 51 undifferentiated connective tissue disease (UCTD) patients, 235 disease controls and 149 healthy blood donors from an Italian cohort. All samples were tested for anti-DFS70 and anti-ENA antibodies using QUANTA Flash assays (Inova Diagnostics, San Diego, CA, USA). Results No differences in the prevalence of anti-DFS70 antibodies were seen among AARD, non-AARD and UCTD (2.1% [7/333] vs. 2.3% [9/384] vs. 5.9% [3/51], respectively; p-value = 0.188). AARD patients positive for anti-DFS70 antibodies showed in all cases an accompanying anti-ENA specificity. In contrast, monospecific anti-DFS70 antibodies showed a significantly different distribution with a clear trend across the main groups (AARD vs. non-AARD vs. UCTD: 0% [0/7] vs. 22% [2/9] vs. 100% [3/3], p = 0.007). Anti-DFS70 antibody levels among AARD, non-AARD and UCTD patients were not significantly different (p = 0.094). Within the anti-DFS70 antibody positive cases, AARD cohort showed a higher variability (median [min-max]: 3.2 [3.2-450.8] CU) compared to non-AARD (median [min-max]: 3.2 [3.2-75.7] CU) and UCTD patients (median [min-max]: 3.2 [3.2-59.0] CU). Conclusions Our preliminary data showed a similar frequency of anti-DFS70 antibodies in AARD, UCTD and non-AARD cohorts. Monospecificity of anti-DFS70 antibodies but not their mere presence is the key element in the diagnostic algorithm. Mono-specific anti-DFS70 antibodies might be a helpful biomarker to discriminate individuals with AARD from non-AARD presenting with a positive ANA.

Identifiants

pubmed: 31318689
doi: 10.1515/cclm-2019-0454
pii: cclm-2019-0454
doi:

Substances chimiques

Antibodies, Antinuclear 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1764-1769

Références

Mahler M, Fritzler MJ. Epitope specificity and significance in systemic autoimmune diseases. Ann N Y Acad Sci 2010;1183:267–87.
Meroni PL, Schur PH. ANA screening: an old test with new recommendations. Ann Rheum Dis 2010;69:1420–2.
Fritzler MJ. The antinuclear antibody test: last or lasting gasp? Arthritis Rheum 2011;63:19–22.
Mahler M, Dervieux T. Comments on recent advances and recommendations for the assessment of autoantibodies to cellular antigens referred as antinuclear antibodies. Ann Rheum Dis 2014;73:e36.
Mahler M, Meroni PL, Bossuyt X, Fritzler MJ. Current concepts and future directions for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies. J Immunol Res 2014;2014:315179.
Ochs RL, Stein TW, Jr., Peebles CL, Gittes RF, Tan EM. Autoantibodies in interstitial cystitis. J Urol 1994;151:587–92.
Conrad K, Rober N, Andrade LE, Mahler M. The clinical relevance of anti-DFS70 autoantibodies. Clin Rev Allergy Immunol 2017;52:202–16.
Ganapathy V, Daniels T, Casiano CA. LEDGF/p75: a novel nuclear autoantigen at the crossroads of cell survival and apoptosis. Autoimmun Rev 2003;2:290–7.
Ochs RL, Muro Y, Si Y, Ge H, Chan EK, Tan EM. Autoantibodies to DFS 70 kd/transcription coactivator p75 in atopic dermatitis and other conditions. J Allergy Clin Immunol 2000;105:1211–20.
O’Rourke DJ, DiJohnson DA, Caiazzo RJ, Jr., Nelson JC, Ure D, O’Leary MP, et al. Autoantibody signatures as biomarkers to distinguish PCa from benign prostatic hyperplasia in patients with increased serum prostate specific antigen. Clin Chim Acta 2012;413:561–7.
Mahler M, Parker T, Peebles CL, Andrade LE, Swart A, Carbone Y, et al. Anti-DFS70/LEDGF antibodies are more prevalent in healthy individuals compared to patients with systemic autoimmune rheumatic diseases. J Rheumatol 2012;39:2104–10.
Albesa R, Sachs U, Infantino M, Manfredi M, Benucci M, Baus Y, et al. Increased prevalence of anti-DFS70 antibodies in young females: experience from a large international multi-center study on blood donors. Clin Chem Lab Med 2019;57:999–1005.
Watanabe A, Kodera M, Sugiura K, Usuda T, Tan EM, Takasaki Y, et al. Anti-DFS70 antibodies in 597 healthy hospital workers. Arthritis Rheum 2004;50:892–900.
Shinohara T, Singh DP, Fatma N. LEDGF, a survival factor, activates stress-related genes. Prog Retin Eye Res 2000;21:341–58.
Ge H, Si Y, Roeder RG. Isolation of cDNAs encoding novel transcription coactivators p52 and p75 reveals an alternate regulatory mechanism of transcriptional activation. EMBO J 1998;17:6723–9.
Daniels T, Zhang J, Gutierrez I, Elliot ML, Yamada B, Heeb MJ, et al. Antinuclear autoantibodies in prostate cancer: immunity to LEDGF/p75, a survival protein highly expressed in prostate tumors and cleaved during apoptosis. Prostate 2005;62:14–26.
Maertens G, Cherepanov P, Pluymers W, Busschots K, De Clercq E, Debyser Z, et al. LEDGF/p75 is essential for nuclear and chromosomal targeting of HIV-1 integrase in human cells. J Biol Chem 2003;278:33528–39.
Muro Y, Ogawa Y, Sugiura K, Tomita Y. HLA-associated production of anti-DFS70/LEDGF autoantibodies and systemic autoimmune disease. J Autoimmun 2006;26:252–7.
Basu A, Drame A, Muñoz R, Gijsbers R, Debyser Z, De Leon M, et al. Pathway specific gene expression profiling reveals oxidative stress genes potentially regulated by transcription co-activator LEDGF/p75 in PCa cells. Prostate 2012;72:597–611.
Singh DP, Ohguro N, Chylack LT, Jr., Shinohara T. Lens epithelium-derived growth factor: increased resistance to thermal and oxidative stresses. Invest Ophthalmol Vis Sci 1999;40:1444–51.
Hendrix J, van Heertum B, Vanstreels E, Daelemans D, De Rijck J. Dynamics of the ternary complex formed by c-Myc interactor JPO2, transcriptional co-activator LEDGF/p75, and chromatin. J Biol Chem 2014;289:12494–506.
Ochs RL, Mahler M, Basu A, Rios-Colon L, Sanchez TW, Andrade LE, et al. The significance of autoantibodies to DFS70/LEDGFp75 in health and disease: integrating basic science with clinical understanding. Clin Exp Med 2016;16:273–93.
Basu A, Sanchez TW, Casiano CA. DFS70/LEDGFp75: an enigmatic autoantigen at the interface between autoimmunity, AIDS, and cancer. Front Immunol 2015;6:116.
Debyser Z, Christ F, De Rijck J, Gijsbers R. Host factors for retroviral integration site selection. Trends Biochem Sci 2015;40: 108–16.
Basu A, Rojas H, Banerjee H, Cabrera IB, Perez KY, De Leon M, et al. Expression of the stress response oncoprotein LEDGF/p75 in human cancer: a study of 21 tumor types. PLoS One 2012;7:e30132.
Bizzaro N, Tonutti E, Tampoia M, Infantino M, Cucchiaro F, Pesente F, et al. Specific chemoluminescence and immunoasdorption tests for anti-DFS70 antibodies avoid false positive results by indirect immunofluorescence. Clin Chim Acta 2015;451:271–7.
Mahler M, Meroni PL, Andrade LE, Khamashta M, Bizzaro N, Casiano CA, et al. Towards a better understanding of the clinical association of anti-DFS70 autoantibodies. Autoimmun Rev 2016;15:198–201.
Bizzaro N, Pesente F, Cucchiaro F, Infantino M, Tampoia M, Villalta D, et al. Anti-DFS70 antibodies detected by immunoblot methods: a reliable tool to confirm the dense fine speckles ANA pattern. J Immunol Methods 2016;436:50–3.
Muro Y, Sugiura K, Morita Y, Tomita Y. High concomitance of disease marker autoantibodies in anti-DFS70/LEDGF autoantibody-positive patients with autoimmune rheumatic disease. Lupus 2008;17:171–6.
Muro Y, Sugiura K, Nakashima R, Mimori T, Akiyama M. Low prevalence of anti-DFS70/LEDGF antibodies in patients with dermatomyositis and other systemic autoimmune rheumatic diseases. J Rheumatol 2013;40:92–3.
Watanabe K, Muro Y, Sugiura K, Tomita Y. IgE and IgG(4) autoantibodies against DFS70/LEDGF in atopic dermatitis. Autoimmunity 2011;44:511–9.
Miyara M, Albesa R, Charuel JL, El Amri M, Fritzler MJ, Ghillani-Dalbin P, et al. Clinical phenotypes of patients with anti-DFS70/LEDGF antibodies in a routine ANA referral cohort. Clin Dev Immunol 2013;2013:703759.
Mahler M, Fritzler MJ. The clinical significance of the dense fine speckled immunofluorescence pattern on HEp-2 cells for the diagnosis of systemic autoimmune diseases. Clin Dev Immunol 2012;2012:494356.
Rigon A, Buzzulini F, Soda P, Onofri L, Arcarese L, Iannello G, et al. Novel opportunities in automated classification of antinuclear antibodies on HEp-2 cell. Autoimmun Rev 2011;10:647–52.
Bentow C, Fritzler MJ, Mummert E, Mahler M. Recognition of the dense fine speckled (DFS) pattern remains challenging: results from an international internet-based survey. Auto Immun Highlights 2016;7:8.
Infantino M, Shovman O, Pérez D, Grossi V, Manfredi M, Benucci M, et al. A better definition of the anti-DFS70 antibody screening by IIF methods. Immunol Methods 2018;461:110–6.
Malyavantham KS, Suresh L. Simultaneous distinction of monospecific and mixed DFS70 patterns during ANA screening with a novel HEp-2 ELITE/DFS70 knockout substrate. J Vis Exp 2018;17:131.
Malyavantham K, Suresh L. Analysis of DFS70 pattern and impact on ANA screening using a novel HEp-2 ELITE/DFS70 knockout substrate. Auto Immun Highlights 2017;8:3.
Bizzaro N, Fabris M. New genetically engineered DFS70 knock-out HEp-2 cells enable rapid and specific recognition of anti-DFS70 antibodies. Autoimmunity 2018;51:152–6.
Infantino M, Shovman O, Gilburd B, Manfredi M, Grossi V, Benucci M, et al. Improved accuracy in DFS pattern interpretation using a novel HEp-2 ELITE system. Clin Rheumatol 2019;38:1293–9.
Mahler M, Andrade LE, Casiano CA, Malyavantham K, Fritzler MJ. Anti-DFS70 antibodies: an update on our current understanding and their clinical usefulness. Expert Rev Clin Immunol 2019;15:241–50.
Egerer K, Roggenbuck D, Hiemann R, Weyer MG, Büttner T, Radau B, et al. Automated evaluation of autoantibodies on human epithelial-2 cells as an approach to standardize cell-based immunofluorescence tests. Arthritis Res Ther 2010;12:R40.
Meroni PL, Bizzaro N, Cavazzana I, Borghi MO, Tincani A. Automated tests of ANA immunofluorescence as throughput autoantibody detection technology: strengths and limitations. BMC Med 2014;12:38.
Fitch-Rogalsky C, Steber W, Mahler M, Lupton T, Martin L, Barr SG, et al. Clinical and serological features of patients referred through a rheumatology triage system because of positive antinuclear antibodies. PLoS One 2014;9:e93812.
Mariz HA, Sato EI, Barbosa SH, Rodrigues SH, Dellavance A, Andrade LE. Pattern on the antinuclear antibody-HEp-2 test is a critical parameter for discriminating antinuclear antibody-positive healthy individuals and patients with autoimmune rheumatic diseases. Arthritis Rheum 2011;63:191–200.
Carter JB, Carter S, Saschenbrecker S, Goeckeritz BE. Recognition and relevance of anti-DFS70 autoantibodies in routine antinuclear autoantibodies testing at a community hospital. Front Med (Lausanne) 2018;5:88eb 11.
Tedeschi SK, Johnson SR, Boumpas DT, Daikh D, Dörner T, Diamond B, et al. Multicriteria decision analysis process to develop new classification criteria for systemic lupus erythematosus. Ann Rheum Dis 2019 (in press).
Infantino M, Shovman O, Pérez D, Manfredi M, Grossi V, Benucci M, et al. Anti-DFS70 autoantibodies in undifferentiated connective tissue diseases subjects: what’s on the horizon? Rheumatology (Oxford) 2018 (in press).
Infantino M, Meacci F, Grossi V, Manfredi M, Li Gobbi F, Sarzi-Puttini PC, et al. The clinical impact of Anti-DFS70 antibodies in undifferentiated connective tissue disease: case reports and a review of the literature. Immunol Res 2017;65:293–5.

Auteurs

Maria Infantino (M)

SOS Laboratorio Immunologia e Allegologia Ospedale S. Giovanni di Dio Firenze, Florence, Italy.

Francesca Pregnolato (F)

Istituto Auxologico Italiano, IRCCS, Experimental Laboratory of Immunorheumatology, Cusano Milanino, Milan, Italy.

Chelsea Bentow (C)

Inova Diagnostics, INC, San Diego, CA, USA.

Michael Mahler (M)

Inova Diagnostics, INC, San Diego, CA, USA.

Maurizio Benucci (M)

SOS Reumatologia Ospedale S. Giovanni di Dio Firenze, Florence, Italy.

Francesca Li Gobbi (F)

SOS Reumatologia Ospedale S. Giovanni di Dio Firenze, Florence, Italy.

Arianna Damiani (A)

SOS Reumatologia Ospedale S. Giovanni di Dio Firenze, Florence, Italy.

Valentina Grossi (V)

SOS Laboratorio Immunologia e Allegologia Ospedale S. Giovanni di Dio Firenze, Florence, Italy.

Franco Franceschini (F)

UOC Reumatologia e Immunologia Clinica - ASST Spedali Civili Brescia, Brescia, Italy.

Caterina Bodio (C)

Istituto Auxologico Italiano, IRCCS, Experimental Laboratory of Immunorheumatology, Cusano Milanino, Milan, Italy.

Maria Orietta Borghi (MO)

Istituto Auxologico Italiano, IRCCS, Experimental Laboratory of Immunorheumatology, Cusano Milanino, Milan, Italy.
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

Mariangela Manfredi (M)

SOS Laboratorio Immunologia e Allegologia Ospedale S. Giovanni di Dio Firenze, Florence, Italy.

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