Recognition of the dense fine speckled (DFS) pattern remains challenging: results from an international internet-based survey
Tóm tắt
The dense fine speckled (DFS) pattern as detected by indirect immunofluorescence (IIF) on HEp-2 cells has been associated with several inflammatory diseases but is most commonly observed in individuals that do not have an antinuclear antibody (ANA)-associated rheumatic disease and even in apparently healthy individuals. Consequently, the accurate identification and correct reporting of this IIF pattern is of utmost importance and accordingly has been recognized by several international study groups for the detection of ANA. Furthermore, the DFS IIF pattern has recently been recommended as a competency level recognition pattern by the International Consensus on Antinuclear Antibody (ANA) Pattern (ICAP,
http://www.anapatterns.org/
) Committee. The objective of this study was to use an internet-based survey to assess how accurately the DFS IIF pattern was recognized by experienced technologists. High-resolution digital IIF images were captured using the automated IIF NOVA View instrument (Inova Diagnostics, San Diego, CA). Ten images were posted in an anonymous, international, internet-based interpretive survey. Two hundred and thirty IIF technologists were invited to participate. Four of the images in the survey were from previously characterized serum samples with classical ANA IIF patterns (nucleolar, centromere, homogeneous, and speckled) and two of the images were from samples with a DFS IIF ANA pattern and isolated anti-DFS70 antibodies as determined by a chemiluminescence immunoassay. The remaining four images were from sera with the classic IIF ANA patterns referred to above and mixed with a monospecific anti-DFS70-positive sample. The survey included multiple choice selections: homogeneous, DFS, centromere, nucleolar, speckled, other, or unrecognizable. 125 of the 230 participants who completed the survey had diverse levels of experience in IIF pattern recognition on HEp-2 cells ranging from <1 year to >10 years of experience (average >10 years). Participants had a high concordance in correctly classifying the classical ANA IIF patterns: ranging from 95.2 % for centromere to 74.4 % for nucleolar patterns. The unmixed DFS pattern was recognized with significantly lower accuracy (~50 %; p < 0.05). However, less than 10 % correctly identified mixed patterns derived from the sera containing both clinically relevant ANA and anti-DFS70 antibodies. Recognizing the DFS ANA IIF pattern and mixed IIF patterns composed of DFS + clinically relevant ANA patterns poses a significant challenge. Consequently, it seems imperative that DFS-specific immunoassays should be used to confirm the presence of anti-DFS70 antibodies before definitive results are reported to physicians.
Tài liệu tham khảo
Agmon-Levin N, Damoiseaux J, Kallenberg C et al (2013) International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies. Ann Rheum Dis 73:17–23
Mahler M, Fritzler MJ (2010) Epitope specificity and significance in systemic autoimmune diseases. Ann N Y Acad Sci 1183:267–287
Meroni PL, Schur PH (2010) ANA screening: an old test with new recommendations. Ann Rheum Dis 69:1420–1422
Slight-Webb S, Lu R, Ritterhouse LL et al (2016) Autoantibody-positive healthy individuals display unique immune profiles that may regulate autoimmunity. Arthritis Rheumatol. doi:10.1002/art.39706
Ochs RL, Muro Y, Si Y et al (2000) Autoantibodies to DFS 70 kd/transcription coactivator p75 in atopic dermatitis and other conditions. J Allergy Clin Immunol 105:1211–1220
Ganapathy V, Casiano CA (2004) Autoimmunity to the nuclear autoantigen DFS70 (LEDGF): what exactly are the autoantibodies trying to tell us? Arthritis Rheum 50:684–688
Chan EK, Damoiseaux J, Carballo OG et al (2015) Report of the first international consensus on standardized nomenclature of antinuclear antibody HEp-2 cell patterns 2014–2015. Front Immunol 6:412
Damoiseaux J, von Muhlen CA, Garcia-de la Torre I et al (2016) International consensus on ANA patterns (ICAP): the bumpy road towards a consensus on reporting ANA results. Autoimmun Highlights 7:1
Mariz HA, Sato EI, Barbosa SH et al (2011) Ana HEp-2 pattern is a critical parameter for discriminating ana-positive healthy individuals and patients with autoimmune rheumatic diseases. Arthritis Rheum 63:191–200
Watanabe A, Kodera M, Sugiura K et al (2004) Anti-DFS70 antibodies in 597 healthy hospital workers. Arthritis Rheum 50:892–900
Muro Y, Sugiura K, Morita Y, Tomita Y (2008) High concomitance of disease marker autoantibodies in anti-DFS70/LEDGF autoantibody-positive patients with autoimmune rheumatic disease. Lupus 17:171–176
Mahler M, Hanly JG, Fritzler MJ (2011) Importance of the dense fine speckled pattern on HEp-2 cells and anti-DFS70 antibodies for the diagnosis of systemic autoimmune diseases. Autoimmun Rev 11:642–645
Tan EM, Cohen AS, Fries JF et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277
Cappelli S, Bellando RS, Martinović D et al (2012) “To be or not to be,” ten years after: evidence for mixed connective tissue disease as a distinct entity. Semin Arthritis Rheum 41:589–598
Vitali C, Bombardieri S, Jonsson R et al (2002) Classification criteria for Sjogren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 61:554–558
Johnson SR, Fransen J, Khanna D et al (2012) Validation of potential classification criteria for systemic sclerosis. Arthritis Care Res (Hoboken) 64:358–367
Fritzler MJ (2016) Choosing wisely: review and commentary on anti-nuclear antibody (ANA) testing. Autoimmun Rev 15:272–280
Mahler M, Parker T, Peebles CL et al (2012) Anti-DFS70/LEDGF antibodies are more prevalent in healthy individuals compared to patients with systemic autoimmune rheumatic diseases. J Rheumatol 39:2104–2110
Mahler M, Radice A, Sinico RA et al (2011) Performance evaluation of a novel chemiluminescence assay for detection of anti-GBM antibodies: an international multicenter study. Nephrol Dial Transplant 27:243–252
Mahler M, Radice A, Yang W et al (2012) Development and performance evaluation of novel chemiluminescence assays for detection of anti-PR3 and anti-MPO antibodies. Clin Chim Acta 413:719–726
Mahler M, Meroni PL, Andrade LE et al (2016) Towards a better understanding of the clinical association of anti-DFS70 autoantibodies. Autoimmun Rev 15:198–201
Bizzaro N, Tonutti E, Tampoia M et al (2015) Specific chemoluminescence and immunoadsorption tests for anti-DFS70 antibodies avoid false positive results by indirect immunofluorescence. Clin Chim Acta 451:271–277
Miyara M, Albesa R, Charuel JL et al (2013) Clinical phenotypes of patients with anti-DFS70/LEDGF antibodies in a routine ANA referral cohort. Clin Dev Immunol. doi:10.1155/2013/703759
Mahler M, Ngo JT, Schulte-Pelkum J et al (2008) Limited reliability of the indirect immunofluorescence technique for the detection of anti-Rib-P antibodies. Arthritis Res Ther 10:R131
Mahler M, Silverman ED, Fritzler MJ (2010) Novel diagnostic and clinical aspects of anti-PCNA antibodies detected by novel detection methods. Lupus 19:1527–1533
Mariz HA, Sato EI, Barbosa SH et al (2011) 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 63:191–200
Bizzaro N, Tonutti E, Villalta D et al (2011) Recognizing the dense fine speckled/lens epithelium-derived growth factor/p75 pattern on HEP-2 cells: not an easy task! Comment on the article by Mariz et al. Arthritis Rheum 63:4036–4037
Ogawa Y, Sugiura K, Watanabe A et al (2004) Autoantigenicity of DFS70 is restricted to the conformational epitope of C-terminal alpha-helical domain. J Autoimmun 23:221–231
Schmeling H, Mahler M, Levy DM et al (2015) Autoantibodies to dense fine speckles in pediatric diseases and controls. J Rheumatol 42:2419–2426
Narain S, Richards HB, Satoh M et al (2004) Diagnostic accuracy for lupus and other systemic autoimmune diseases in the community setting. Arch Intern Med 164:2435–2441