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Found in patients with SLE, chronic autoimmune hepatitis or juvenile idiopathic arthritis.
If SLE is clinically suspected, it is recommended to perform a follow-up test for anti-dsDNA antibodies, alone or in combination with dsDNA/histone complexes (nucleosomes/chromatin); anti-dsDNA antibodies are included in the classification criteria for SLE.
Petri, Orbai, Alárcon et al., 2012Conrad, Schössler & Hiepe, 2015
If chronic autoimmune hepatitis or juvenile idiopathic arthritis is suspected, follow-up testing is not recommended because the respective autoantigens revealing the AC-1 pattern are not completely defined.
Conrad, Schössler & Hiepe, 2017
Although autoantibodies to Topoisomerase I (formerly Scl-70) may be reported as nuclear homogeneous, they typically reveal a composite AC-29 HEp-2 IIFA pattern; as such, clinical suspicion of SSc may warrant follow-up testing for reactivity to this antigen.
Andrade, Klots, Herold et al., 2018Dellavance, Gallindo, Soares et al., 2009
Although AC-1 is the most prevalent pattern in chronic autoimmune hepatitis, other HEp-2 IIFA patterns may occur, but also for these patterns the autoantigens are not completely defined.
EASL Clinical Practice Guidelines: Autoimmune hepatitis, 2015.
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Commonly found as high titer HEp-2 IIFA-positive in apparently healthy individuals or in patients who do not have a systemic autoimmune rheumatic disease (SARD).
Mariz, Sato, Barbosa et al., 2011.
The negative association with SARD is only valid if the autoreactivity is confirmed as being directed to DFS70 (also known as LEDGF/p75) and if no other common ENA is recognized.
Watanabe, Kodera, Sugiura et al., 2004Mahler, Parker, Peebles et al., 2012
Both in apparently healthy individuals as well as patients who do not have a SARD the AC-2 pattern may be caused by autoantibodies to other antigens than DFS70.
Ochs, Mahler, Basu et al., 2016
Confirmatory assays for anti-DFS70 antibodies may be available only in specialty clinical laboratories.
Damoiseaux, Andrade, Carballo et al., 2019
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Commonly found in patients with limited cutaneous SSc, and as such included in the classification criteria for SSc.
van den Hoogen, Khanna, Fransen et al., 2013Conrad, Scho?ssler & Hiepe, 2015Johnson, Fransen, Khanna et al., 2012
In combination with Raynaud phenomenon, the AC-3 pattern is prognostic for onset of limited cutaneous SSc.
Conrad, Schössler & Hiepe, 2015Johnson, Fransen, Khanna et al., 2012
Strongly associated with antibodies to CENP-B; especially in case of low titers, confirmation by an antigen-specific immunoassay is recommended to support the association with limited cutaneous SSc; the CENP-B antigen is included in many routine ENA profiles.
Conrad, Schössler & Hiepe, 2015
The AC-3 pattern is also apparent in a subset of patients with PBC; these patients often have both SSc as well as PBC.
Conrad, Schössler & Hiepe, 2015
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The AC-3 pattern is found in a subset of patients with SjS; these patients show mild SSc features, but a full-blown SjS clinical feature, more severe exocrine glandular dysfunction, and high risk of lymphoma.
Vasiliki-Kallipi, Diamanti, Vlachoyiannopoulos et al.2010Baldini, Mosca, Della Rossa et al., 2013Lee, Kang, Lee et al., 2015Baer, Medrano, McAdams-Demarco et al., 2016
The AC-3 pattern is also apparent in a subset of patients with SLE; these patients often have some degree of overlap with SSc.
Nakano, Ohuchi, Hasegawa et al., 2000
Most sera with the AC-3 pattern react with CENP-A and CENP-B; antibodies to CENP-A can be detected by ELISA or disease specific immunoassays (i.e., SSc profile).
Mahler, Maes, Blockmans et al., 2000Perosa, Prete, Di Lernia et al., 2016
In rare cases AC-3 positive, but CENP-B negative sera of SSc patients may be strongly positive for anti-CENP-A antibodies.
Russo, Hoch, Varga et al., 2000Hudson, Mahler, Pope et al., 2012
Antibodies to CENP-C have been reported in patients with SSc and SjS.
Pillemer, Casciola-Rosen, Baum et al., 2004Gelber, Pillemer, Baum et al., 2006Tanaka, Muro, Suzuki et al., 2017
Availability of assays for CENP-A, i.e., ELISA or SSc profile, may be limited to specialty clinical laboratories; specific immunoassays for anti-CENP-C antibodies are currently not commercially available.
Damoiseaux, Andrade, Carballo et al., 2019
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Present to a varying degree in distinct SARD, in particular SjS, SLE, subacute cutaneous lupus erythematosus, neonatal lupus erythematosus, congenital heart block, DM, SSc, and SSc-AIM overlap syndrome.
Conrad, Schössler & Hiepe, 2015
If SjS, SLE, subacute cutaneous lupus erythematosus, neonatal lupus erythymatosus, or congenital heart block is clinically suspected, it is recommended to perform follow-up tests for anti-SS-A/Ro (Ro60) and anti-SS-B/La antibodies; in most laboratories these antigens are included in the routine ENA profile.
Conrad, Schössler & Hiepe, 2015
Autoantibodies to SS-A/Ro are part of the classification criteria for SjS (the criteria do not distinguish between Ro60 and Ro52/TRIM21).
Shiboski, Shiboski, Seror et al., 2016
If SSc, AIM, or to a lesser extend SLE, is clinically suspected, it is recommended to perform follow-up tests for detecting autoantibodies to Mi-2, TIF1?, and Ku; these antigens are typically included in disease specific immunoassays (i.e., inflammatory myopathy profile).
Betteridge & McHugh, 2016
Autoantibodies to Mi-2 and TIF1? are associated with DM; autoantibodies to TIF1? in patients with DM, although rare in the overall AC-4 pattern, is strongly associated with malignancy in old patients.
Betteridge & McHugh, 2016Trallero-Araguás, Rodrigo-Pendás, Selva-O’Callaghan et al., 2012
Autoantibodies to Ku are associated with SSc-AIM and SLE-SSc-AIM overlap syndromes.
Betteridge & McHugh, 2016
Anti-SS-A/Ro (Ro60) and AIM-specific autoantibodies may be undetected in HEp-2 IIFA-screening.
Bossuyt, Frans, Hendrickx et al., 2004
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Present to a varying degree in distinct SARD, in particular SLE, SSc, MCTD, SSc-AIM overlap syndrome, and UCTD (i.e, patients with rheumatic symptoms without a definite SARD diagnosis).
Northway & Tan, 1972
If SLE is clinically suspected, it is recommended to perform follow-up tests for anti-Sm and anti-U1RNP antibodies; these antigens are commonly included in the routine ENA profile; anti-Sm antibodies are included in the classification criteria for SLE.
Satoh, Fritzler & Chan, 2011 Petri, Orbai , Alarcón et al., 2012Satoh, Vázquez-Del Mercado & Chan, 2009
If SSc is clinically suspected, it is recommended to perform a follow-up test for anti-RNApol III antibodies (e.g., SSc profile*); the anti-RNApol III antibodies are included in the classification criteria for SSc.
van den Hoogen, Khanna, Fransen et al., 2013
If MCTD is clinically suspected, it is recommended to perform a follow-up test for anti-U1RNP antibodies; the antigen is commonly included in the routine ENA profile; anti-U1RNP antibodies are included in the diagnostic criteria for MCTD.
Sharp, Irvin, Tan et al., 1972
If the SSc-AIM overlap syndrome is clinically suspected, it is recommended to perform follow-up tests for anti-U1RNP and anti-Ku antibodies; these antigens are included in the routine ENA profile (U1RNP), or in disease specific immunoassays (Ku, i.e., inflammatory myopathy profile and SSc profile)
Betteridge & McHugh, 2016Satoh, Tanaka, Ceribelli et al., 2017
In non-SARD individuals in the general population, the presence of the AC-5 pattern is not associated with the autoantigens mentioned above and most often concerns low antibody titers.
Damoiseaux, Andrade, Carballo et al., 2019
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Occasionally, autoantibodies revealing the AC-5 pattern are reactive with RNP other than U1RNP, for instance U2RNP (associated with SSc-AIM overlap syndrome) or U11/U12RNP (associated with SSc); these autoantibodies can be detected by immunoprecipitation.
Mimori, Hinterberger, Pettersson et al., 1984Fretig, Domsic, Rodriguez-Reyna et al., 2009
Specific immunoassays for these autoantibodies are currently not commercially available.
Damoiseaux, Andrade, Carballo et al., 2019
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Found in a broad spectrum of autoimmune diseases, including PBC, AIM (DM), as well as other inflammatory conditions.
Cozzani, Drosera, Riva et al., 2012
If PBC is clinically suspected, it is recommended to perform follow-up tests for anti-Sp100 (and PML/ Sp140) antibodies; in particular anti-Sp100 antibodies have the best clinical association with PBC and have added value, especially when associated with AMA; the Sp100 (and PML-Sp140) antigen is included in disease specific immunoassays (ie, liver profile).
Conrad, Schössler W & Hiepe, 2015Hu, Zhao, Hu et al., 2014Granito, Yang, Muratori et al., 2010.
If DM is clinically suspected, it is recommended to perform a follow-up test for anti-MJ/NXP-2 antibodies; these anti-MJ/NXP-2 antibodies are highly specific for AIM, are found in up to one third of patients with juvenile DM, and have been reported to be associated with malignancies in adult AIM patients; the antigen is included in disease specific immunoassays (i.e., inflammatory myopathy profile).
Ichimura, Matsushita, Hamaguchi et al., 2012Benveniste, Stenzel & Allenbach, 2016.Ceribelli, Fredi, Taraborelli et al., 2012
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The AC-7 pattern has low positive predictive value for any disease.
Onouchi, Muro & Tomita, 1999Fujimoto, Kikuchi, Tamaki et al., 1997
Antigens primarily localized in the dots include p80-coilin and SMN complex; specific immunoassays for these autoantibodies are currently not commercially available.
Andrade, Chan, Raska et al., 1991Satoh, Chan, Ross et al., 2011
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Anti-p80-coilin antibodies may rarely occur in SLE, (localized linear) SSc, and SjS.
Andrade, Chan, Raska et al., 1991Fujimoto, Kikuchi, Tamaki et al., 1997Onouchi, Muro & Tomita, 1999
Isolated (without anti-snRNPs) anti-SMN antibodies are reported in patients with AIM or SSc-AIM overlap syndrome.
Satoh, Chan, Ross et al., 2011
The specificity of antibodies to p80-coilin and the SMN complex can be confirmed by Western blot, solid phase immunoassays using recombinant proteins and immunoprecipitation.
Andrade, Chan, Raska et al., 1991Satoh, Chan, Ross et al., 2011Amlani, Hazlewood, Hamilton et al., 2018
Most reports describe autoantibodies directly binding to specific antigens (i.e. antigen-specific immunoassays) and do not actually show clear correlations with the AC-7 pattern as such; specific immunoassays for these autoantibodies are currently not commercially available.
Damoiseaux, Andrade, Carballo et al., 2019
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Found in patients with SSc, SSc-AIM overlap syndrome, and patients with clinical manifestations of other SARD.
Mahler, Fritzler & Satoh, 2015Ceribelli, Cavazzana, Franceschini et al., 2010Mahler & Raijmakers, 2010
If limited cutaneous SSc is clinically suspected, it is recommended to perform a follow-up test for anti-Th/ To antibodies; the antigen is included in disease specific immunoassays (ie, SSc profile).
Mahler, Fritzler & Satoh, 2015Ceribelli, Cavazzana, Franceschini et al., 2010
If SSc-AIM overlap syndrome is clinically suspected, it is recommended to perform a follow-up test for anti-PM/Scl antibody reactivity; the antigen may be included in the routine ENA profile and is included in disease specific immunoassays (i.e., inflammatory myopathy profile* and the SSc profile); in general, anti- PM/Scl antibodies yield a diffuse nuclear fine speckled staining in addition to the AC-8 pattern.
Mahler & Raijmakers, 2010
Other antigens recognized include B23/nucleophosmin, No55/SC65, and C23/nucleolin, but the clinical significance of these autoantibodies is not well established; specific immunoassays for these autoantibodies are currently not commercially available.
Damoiseaux, Andrade, Carballo et al., 2019
Although some anti-Th/To antibody immunoassays are commercially available, technical issues relating to the limited sensitivity of these immunoassays should be taken in to consideration.
Mahler, Fritzler & Satoh, 2015Mahler, Gascon, Patel et al., 2013
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The AC-8 pattern that is the result of the anti-Th/To reactivity is also seen in patients with SLE, UCTD (i.e., patients with rheumatic symptoms without a SARD diagnosis), SSc sine scleroderma, idiopathic interstitial lung disease or pulmonary hypertension.
Fischer, Pfalzgraf , Feghali-Bostwick et al., 2006Fischer, Meehan, Feghali-Bostwick et al., 2006
Patients with autoantibodies revealing the AC-8 pattern due to anti-PM/Scl reactivity may have, in addition to the clinical features of AIM and SSc, various clinical manifestations of SLE and SjS.
Mahler & Raijmakers, 2007
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Found in patients with SSc.
Okano, Steen & Medsger, 1992
If SSc is clinically suspected, it is recommended to perform a follow-up test for anti-U3RNP/fibrillarin antibodies; the antigen is included in disease specific immunoassays (i.e, SSc profile)
Okano, Steen & Medsger, 1992
If confirmed as anti-U3RNP/fibrillarin reactivity by immunoassay, the clinical association is with diffuse SSc, increased incidence of pulmonary arterial hypertension, skeletal muscle disease, severe cardiac involvement, and gastrointestinal dysmotility.
Johnson, Fransen, Khanna et al., 2012 Okano, Steen & Medsger, 1992Arnett, Reveille, Goldstein et al., 1996 Tormey, Bunn, Denton et al., 2001
Among SSc patients, anti-U3RNP/fibrillarin antibodies are most commonly found in African American and Latin American patients
Okano, Steen & Medsger, 1992Arnett, Reveille, Goldstein et al., 1996Nandiwada, Peterson, Mayes et al., 2016
Although some anti-U3RNP/fibrillarin immunoassays are commercially available, technical issues relating to the limited sensitivity of these immunoassays should be taken into consideration.
Mehra, Walker, Patterson et al., 2013
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The AC-10 pattern can be seen in various conditions, including SSc, Raynaud’s phenomenon, SjS, and cancer.
Reimer, Rose, Scheer et al., 1987Kuwana, Kaburaki, Mimori et al., 1993Fritzler, von Munlen, Toffoli et al., 1995Fujii, Mimori & Akizuki, 1995 Imai, Ochs, Kiyosawa et al., 1996
If the AC-10 pattern is observed in the serum of patients with conditions mentioned above, follow-up testing for anti-NOR90 (hUBF) antibodies is to be considered; the antigen is included in disease specific immunoassays (i.e. SSc profile).
Fritzler, von Munlen, Toffoli et al., 1995Fujii, Mimori & Akizuki, 1995
While AC-10 is associated with anti-RNApol I antibodies, these antibodies almost always coexist with anti-RNApol III antibodies which reveal the AC-5 pattern; therefore, if SSc is clinically suspected, it is recommended to perform a follow-up test for anti-RNApol III antibodies (See also AC-5); specific immunoassays for anti-RNA pol I antibodies are currently not commercially available.
Reimer, Rose, Scheer et al., 1987 Kuwana, Kaburaki, Mimori et al., 1993Yamasaki, Honkanen-Scott, Hernandez et al., 2006
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The AC-11 pattern is infrequently found in routine autoantibody testing and has been described in autoimmune-cytopenias, autoimmune liver diseases, linear scleroderma, APS, and SARD; current information on clinical associations is based mainly on case reports and small cohorts.
Coppo, Clauvel, Bengoufa et al., 1987Konstantinov, Foisner, Byrd, et al., 1995 Reeves, Chaudhary, Salerno et al., 1987
Antigens recognized include lamins (A, B, C) and LAP-2; specific immunoassays for these autoantibodies are currently not commercially available.
Coppo, Clauvel, Bengoufa et al., 1987Konstantinov, Foisner, Byrd, et al., 1995Reeves, Chaudhary, Salerno et al., 1987
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Found in patients with PBC, as well as patients with other autoimmune liver diseases and SARD.
Miyachi, Hankins, Matsushima et al., 2003
If PBC is clinically suspected, it is recommended to perform a follow-up test for anti-gp210 antibodies; the antigen is included in disease specific immunoassays (ie, extended liver profile).
Courvalin, Lassoued, Bartnik et al., 1990Nickowitz & Worman, 1993Bandin, Courvalin, Poupon et al., 1996
Other antigens recognized include p62 nucleoporin, LBR, and Tpr; specific immunoassays for these autoantibodies are currently not commercially available.
Wesierska-Gadek, Klima, Komina et al., 2007Kraemer & Tony, 2010Courvalin, Lassoued, Worman et al., 1990Ou, Enarson, Rattner et al., 2004
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Anti-p62 nucleoporin antibodies have been described in PBC and SLE.
Wesierska-Gadek, Klima, Komina et al., 2007Kraemer & Tony, 2010
Anti-LBR antibodies have been described in PBC.
Courvalin, Lassoued, Worman et al., 1990
Anti-Tpr antibodies have been described in PBC, autoimmune liver disease, SLE, SSc and SjS.
Ou, Enarson, Rattner et al., 2004
Most reports describe autoantibodies directly binding to specific antigens (i.e., antigen-specific immunoassays) and do not actually show clear correlations with the AC-12 pattern as such; specific immunoassays for these autoantibodies are currently not commercially available.
Damoiseaux, Andrade, Carballo et al., 2019
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The AC-13 pattern has formerly been considered highly specific for SLE, but this specificity is debated.
Miyachi, Fritzler & Tan, 1978 Vermeersch, Beeck, Lauwerys et al., 2009
If SLE is clinically suspected, it is recommended to perform a follow-up test for anti-PCNA antibodies; the antigen is included in several routine ENA profiles.
Miyachi, Fritzler & Tan, 1978
Recent studies with antigen-specific immunoassays show clinical associations also with SSc, AIM, RA, HCV, and other conditions.
Vermeersch, Beeck, Lauwerys et al., 2009Mahler, Burlingame, Wu et al., 2011Mahler, Miyachi, Peebles et al., 2013Hsu, Tsay, Chen et al., 2006
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A major challenge in deriving an association of the AC-13 pattern with antibodies to the classical 35 kDa PCNA (elongation factor of DNA polymerase delta auxiliary protein) is that “PCNA” is known to be a macromolecular complex where targets other than the ‘classical’ 35 kDa PCNA are present. In addition, a number of other apparently unrelated targets can also produce an AC-13-like pattern by HEp-2 IIFA.
Takeuchi, Kaneda, Kawakami et al., 1996.
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The majority of sera exhibiting the AC-14 pattern are from patients with a diversity of neoplastic conditions (breast, lung, colon, lymphoma, ovary, brain); paradoxically, the frequency of the AC-14 pattern in patient cohorts with these malignancies is low. The AC-14 pattern is also seen in inflammatory conditions (Crohn’s disease, autoimmune liver disease, SjS, graft-versus-host disease); current information on clinical associations is based mainly on case reports and series of cases.
Casiano et al., 1993 Casiano et al., 1995 Rattner et al., 1997 Bencimon et al., 2005 Welner et al., 2013
Possible associations only hold if the reactivity to CENP-F is confirmed in an antigen-specific immunoassay; current information on clinical associations is based mainly on case reports and series of cases; specific immunoassays for this autoantibody are currently not commercially available.
Damoiseaux, Andrade, Carballo et al., 2019
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Found in patients with AIH type 1, chronic HCV infection, and celiac disease (IgA isotype); rare in SARD.
Conrad, Schössler & Hiepe, 2017
If AIH type 1 is clinically suspected, it is recommended to confirm reactivity with smooth muscle antibodies (IgG isotype), typically detected by IIFA on rodent tissue (liver, stomach, kidney); anti-smooth muscle antibodies are included in the international criteria for AIH type 1.
Conrad, Schössler & Hiepe, 2017 Liberal, Grant, Longhi et al., 2014
F-actin is the main target antigen of anti-smooth muscle antibodies in AIH type 1; autoantibodies to F-actin are of more clinical importance than antibodies to G-actin.
Lidman, Biberfeld, Fagraeus et al., 1976Fusconi, Cassani, Zauli et al., 1990Chretien-Leprince, Ballot, Andre et al., 2005
Although anti-F-actin immunoassays are commercially available, technical issues relating to the sensitivity of these immunoassays should be taken into consideration.
Damoiseaux, Andrade, Carballo et al., 2019
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High prevalence of IgA and/or IgG type anti-actin antibody has been reported in celiac disease.
Pedreira, Sugai, Moreno et al., 2005Clemente, Musu, Frau et al., 2000
Autoantibodies to non-muscle myosin have been described in 3 patients with HCV-positive chronic hepatitis/liver cirrhosis.
von Muhlen, Chan, Peebles et al., 1995
Monoclonal antibodies to non-muscle myosin have been reported in chronic lymphocytic leukemia.
Chu, Catera, Hatzi et al., 2008
Specific immunoassays for non-muscle myosin are currently not commercially available.
Damoiseaux, Andrade, Carballo et al., 2019
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Found in various diseases, but AC-16 is not typically found in SARD.
Damoiseaux, Andrade, Carballo et al., 2019
Antigens recognized include cytokeratins 8, 18, & 19, tubulin, and vimentin; specific immunoassays for these autoantibodies are currently not commercially available.
Damoiseaux, Andrade, Carballo et al., 2019
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Higher levels of anti-cytokeratin 8, anti-cytokeratin 18 and anti-cytokeratin 19 antibodies reported in patients with AIH compared with normal volunteers and patients with chronic active HCV infection.
Murota, Nishioka, Fujita et al., 2001
Autoantibody against the 45-kDa human cytokeratin 18 protein reported in 76% of chronic obstructive pulmonary disease patients and 24% of control subjects.
Kuo, Chang, Wu et al., 2010
Higher levels of anti-cytokeratin 19 antibodies reported in patients with idiopathic pulmonary fibrosis and pulmonary fibrosis associated with collagen vascular disorders compared with healthy controls, patients with chronic bronchitis, and patients with pneumonia
Fujita, Dobashi, Ohtsuki et al., 1999
Reported in 50% of sera from patients with alcoholic liver disease, but in only 7 – 13% of sera from patients with chronic active hepatitis, PBC, and healthy controls.
Kurki, Miettinen, Salaspuro et al., 1983
Reported in high prevalence in patients with certain parasitic infections.
Howard, Gull & Miles, 1987
IgM autoantibodies to tubulin have been described in patients with infectious mononucleosis and healthy adults.
Mead, Cowin & Whitehouse, 1980
IgG autoantibodies to tubulin have been detected specifically associated with young age onset of nasopharyngeal carcinoma.
Jalbout, Bel Hadj, Bouaouina et al., 2002
Reported in a single case of a patient with a progressive sensorimotor neuropathy.
Stubbs, Fisher & Siegel, 1998
High levels of polyclonal autoantibodies to tubulin are associated with acquired demyelinating polyneuropathies.
Connolly & Pestronk, 1997 Manfredini, Nobile-Orazio, Allaria et al., 1995
Low levels of autoantibodies are reported in healthy controls.
Karsenti, Guilbert, Bornens et al., 1977
Reported as one of the biomarkers for Sydenham’s chorea and PANDAS syndrome
Kirvan, Cox, Swedo et al., 2007
IgG and IgM autoantibodies to vimentin have been reported as relevant markers in patients with neurofibromatosis type 1 and associated tumors.
Kotaska, Petrak, Kukacka et al., 2007
Rheumatoid arthritis and other inflammatory arthritis patients may have antibody to citrullinated isoforms of vimentin; it is, however, unlikely that these antibodies show the AC-16 pattern.
Tilleman, Steendam, Cantaert et al., 2008
Reported to occur after solid organ transplantation and implicated in rejection and poor outcome in cardiac or renal transplantation.
Mahesh, Leong, McCormack et al., 2007 Besarani, Cerundolo, Smith et al., 2014
Most reports describe autoantibodies directly binding to specific antigens (i.e., antigen-specific immunoassays) and none actually shows correlations with the AC-16 pattern as such; specific immunoassay for these autoantibodies are currently not commercially available.
Damoiseaux, Andrade, Carballo et al., 2019
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Found very infrequently in a routine serology diagnostic setting. Antigens recognized include ?-Actinin and Vinculin; specific immunoassays for these autoantibodies are currently not commercially available
Damoiseaux, Andrade, Carballo et al., 2019
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In SLE and lupus nephritis cross-reactive anti-?-actinin and anti-dsDNA autoantibodies have been reported as pathogenic
Zhao, Weinstein, Tuzova et al., 2005
Reported as part of the anti-cell membrane antibody spectrum that characterize patients with lupus nephritis; also reported as a biomarker to differentiate patients with lupus nephritis from those without renal involvement
Seret, Canas, Pougnet-Di Costanzo et al., 2015 Zhang, Pan, Zhao et al., 2010
Reported with relatively high prevalence (~40%) in patients with AIH type 1 and associated with more severe disease, clinical and histological disease activity, predictor of therapeutic response, and double positivity with anti-ssDNA antibodies Autoantibodies to vinculin:
Gueguen, Dalekos, Nousbaum et al., 2006Renaudineau, Dalekos, Gueguen et al., 2008Zachou, Oikonomou, Renaudineau et al., 2008
Reported in 2 of 31 patients with chronic inflammatory demyelinating neuropathy
Beppu, Sawai, Satoh et al ., 2015
Most reports describe autoantibodies directly binding to specific antigens (i.e. antigen-specific immunoassays) and none actually shows correlations with the AC-17 pattern as such; specific immunoassays for these autoantibodies are currently not commercially available.
Damoiseaux, Andrade, Carballo et al., 2019
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Autoantibodies revealing the AC-18 pattern have been reported in distinct SARD and in a variety of other diseases; their prevalence in unselected or specified disease cohorts has not been thoroughly studied
Bhanji, Eystathioy, Chan et al., 2007
Antigens recognized include GW-body (Processing or P body) antigens (Ge- 1/Hedls, GW182, and Su/Ago2) and endosomal antigens (EEA1, CLIP-170, GRASP-1, and LBPA); specific immunoassays for these autoantibodies are currently not commercially available
Damoiseaux, Andrade, Carballo et al., 2019
Autoantibodies to GW-bodies and endosomes may yield slightly different HEp-2 IIFA patterns.
Bhanji, Eystathioy, Chan et al., 2007Stinton, Eystathioy, Selak et al., 2004
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Autoantibodies to GW bodies. The most common clinical presentations in a single study with 55 positive sera were neurological symptoms (i.e. ataxia, motor and sensory neuropathy; 33%), SjS (31%), and the remainder had a variety of other diagnoses including SLE, RA, and PBC.
Bhanji, Eystathioy, Chan et al., 2007
Autoantibodies to GW bodies. Analysis by ALBIA and immunoprecipitation of recombinant proteins indicated that autoantibodies were directed against Ge-1/Hedls (58%), GW182 (40%), and Su/Ago2 (16%)
Bhanji, Eystathioy, Chan et al., 2007
Autoantibodies to endosomal components.Autoantibodies to EEA1 were seen in a variety of conditions, but ~40% of the patients had a neurological disease.
Stinton, Eystathioy, Selak et al., 2004
Autoantibodies to endosomal components. Autoantibodies to CLIP-170 were reported in 4 patients with different diseases including the prototype patient with SLE and AIM; the remaining 3 patients had limited cutaneous SSc, glioblastoma, and idiopathic pleural effusion.
Griffith, Ryan, Senecal et al., 2002
Autoantibodies to endosomal components. Autoantibodies to both LBPA and GRASP-1 have not been studied thoroughly in unselected or specified disease cohorts; anti-GRASP-1 autoantibodies were detected in 17% of PBC sera.
Stinton, Selak & Fritzler, 2005 Stinton, Swain, Myers et al. 2011
Most reports describing autoantibodies directly binding to specific endosomal antigens do not show correlations with the AC-18 pattern as such; specific immunoassays for the autoantibodies reacting with antigens of GW bodies or endosomes are currently not commercially available.
Damoiseaux, Andrade, Carballo et al., 2019
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Found in patients with SLE and the anti-synthetase syndrome (a subset of AIM), interstitial lung disease, polyarthritis, Raynaud’s phenomenon, and mechanic’s hands; these features may occur in various combinations or as an isolated manifestation, especially interstitial lung disease.
Satoh, Tanaka, Ceribelli et al., 2017 Sciascia, Bertolaccini, Roccatello et al, 2014Yura, Sakamoto, Satoh et al., 2017
If SLE is clinically suspected, follow-up tests for antibodies to ribosomal P phosphoproteins (P0, P1, P2, C22 RibP peptide) are recommended; these antigens may be included in the routine ENA profile.
Damoiseaux, Andrade, Carballo et al., 2019
Anti-RibP antibodies have been associated in some studies with neuropsychiatric lupus, and in childhood-onset SLE with autoimmune hemolytic anemia.
Sciascia, Bertolaccini, Roccatello et al, 2014 Mahler, Kessenbrock, Szmyrka et al., 2006Valões, Molinari, Pitta et al., 2017
If AIM, in particular the anti-synthetase syndrome, is suspected, it is recommended to perform follow-up tests for antibodies to tRNA synthetases; antigens are included in disease specific immunoassays (ie, inflammatory myopathy profile).
Betteridge & McHugh, 2016Satoh, Tanaka, Ceribelli et al., 2017
If AIM, in particular necrotizing myopathy, is suspected, it is recommended to perform follow-up tests for anti-SRP antibodies; the antigen is included in disease specific immunoassays (ie, inflammatory myopathy profile).
Betteridge & McHugh, 2016 Satoh, Tanaka, Ceribelli et al., 2017
The fine distinction between AC-19 and -20 may depend on HEp-2 substrates and/or antibody concentration; antibodies to both RibP as well as tRNA synthetases may be undetected in HEp-2 IIFA-screening.
Damoiseaux, Andrade, Carballo et al., 2019
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Anti-RibP antibodies have been reported in 10% of AIH patients without clinical or laboratory evidence of SLE
Calich, Viana, Cancado et al., 2013
The prevalence of anti-RibP antibodies in SLE has been reported to range between 8 – 35% in a multicenter study
Mahler, Kessenbrock, Szmyrka et al., 2006
Less than 60% of the sera positive for anti-RibP antibodies have the AC-19 pattern at serum screening dilutions of 1/80 or higher; the coexistence of a weak nucleolar staining is relatively common
Damoiseaux, Andrade, Carballo et al., 2019
Less than 50% of sera having anti-tRNA synthetase antibodies have an AC-19 pattern at serum screening dilutions of 1/80 or higher
Fritzler, Choi & Mahler, 2018
Most reports describing clinical association of anti-RibP antibodies do not actually show correlations with the AC-19 pattern as such.
Damoiseaux, Andrade, Carballo et al., 2019
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Found in patients with the anti-synthetase syndrome (a subset of AIM), interstitial lung disease, polyarthritis, Raynaud’s phenomenon, and mechanic’s hands; these features may occur in various combinations or as an isolated manifestation, especially interstitial lung disease
Satoh, Tanaka, Ceribelli et al., 2017Marie, Hatron, Cherin et al., 2013
Autoantibodies associated with the AC-20 pattern are primarily reported for the anti-Jo-1 antibody, which recognizes histidyl-tRNA synthetase; since AC-20 is not specific for Jo-1, it is recommended to perform a follow-up test for anti-Jo-1 antibodies; the antigen is included in the routine ENA profile, as well as in disease specific immunoassays (i.e., inflammatory myopathy profile*); the anti-Jo-1 antibodies are included in the classification criteria for AIM.
Fritzler, Choi, Mahler et al., 2018Lundberg, Tjaärnlund, Bottai et al., 2017
The fine distinction between AC-19 and -20 may depend on HEp-2 substrates and/or antibody concentration; antibodies to Jo-1 may be undetected in HEp-2 IIFA-screening.
Damoiseaux, Andrade, Carballo et al., 2019
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Commonly found in PBC, but also detected in SSc, including PBC-SSc overlap syndrome and PBC-SjS overlap syndrome
European Association for the Study of the Liver, 2017Shuai et al., 2017Skare et al., 2011Zheng et al., 2017Nardi et al., 2006
If PBC is clinically suspected it is recommended to perform a follow-up test for AMA, historically detected by IIFA on rodent tissue (liver, stomach, kidney); these autoantibodies are primarily directed to the PDH complex, and in particular the E2-subunit (PDH-E2); the antigen is included in disease specific immunoassays (i.e., liver profile*) as well as in some routine ENA profiles
European Association for the Study of the Liver, 2017Shuai et al., 2017
Additional antigens recognized include the E1? and E1? subunits of PDH, the E3-binding protein of PDH, and the 2-OGDC; these antigens are only included in extended disease specific immunoassays (i.e., extended liver profile*)
European Association for the Study of the Liver, 2017Shuai et al., 2017
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Found in small numbers of patients with a variety of conditions
Stinton et al., 2004
Antigens recognized include giantin/macrogolgin and distinct golgin molecules; specific immunoassays to detect autoantibodies directed to specific Golgi antigens are currently not commercially available
Covini et al., 2012Calise et al., 2015Novembrino et al., 2014Keppeke et al., 2016
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The AC-22 pattern has been reported in small numbers of patients with a variety of conditions, including SjS, SLE, RA, MCTD, GPA, idiopathic cerebellar ataxia, paraneoplastic cerebellar degeneration, adult Still’s disease, and viral infections including HIV and EBV
Stinton et al., 2004Fritzler et al., 1984Vermeersch et al., 2003Staub et al., 2003
Although possibly biased by the referral pattern, one study concluded that the AC-22 pattern is not clinically associated with SARD as there were only 1 SjS and 2 RA diagnoses among their 20 AC-22 positive cases collected over 10-years and a clinical follow-up observation ranging from 0 – 10 years; the remaining cases showed diverse diagnoses including 2 carcinomas
Vermeersch et al., 2011
The AC-22 pattern is rare in the general population
Satoh et al., 2012
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Most commonly found in HCV patients who have been treated with pegylated interferon-?/ribavirin combination therapy, but autoantibodies revealing the AC-23 patterns were undetected prior to treatment; as the use of interferon-?/ribavirin in HCV treatment is decreasing, the frequency and clinical associations of the AC-23 pattern may change
Covini et al., 2012Calise et al., 2015Novembrino et al., 2014Keppeke et al., 2016
Specific immunoassays to detect autoantibodies directed to specific Rods and Rings antigens, for instance IMPDH2, are not commercially available
Presence of the AC-23 pattern depends on the HEp-2 cell substrate.
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HCV patients positive for the AC-23 pattern have been reported to have disease that is more resistant to therapy, but this is not confirmed in other cohorts
Climent et al. 2016
The AC-23 pattern has also been reported rarely in individuals without HCV infection, including SLE patients and patients under treatment with mycophenolic acid, azathioprine, methotrexate or acyclovir, as well as with lower titers in the general population
Satoh et al., 2012Climent et al. 2016Covini et al., 2012Keppeke et al., 2016
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The AC-24 pattern has low positive predictive value for any disease
Within the spectrum of the SARD, the AC-24 pattern is found in patients with Raynaud’s phenomenon, localized scleroderma, SSc, SLE and RA, either alone or in combination with other SSc-associated antibodies; 102–105
Takahashi et al. 2016Howng et al., 2011Hamaguchi et al., 2015Gavanescu et al., 1999
Antigens recognized include ?-enolase, ?-enolase, ninein, Cep-250, Mob1, PCM-1/2, pericentrin; specific immunoassays for these autoantibodies are currently not commercially available
Hamaguchi et al., 2015Fritzler et al., 2003Rattner et al., 1991Mack et al., 1998
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Possible association with infections; described in children with Mycoplasma pneumoniae infection
Cimolai, Mah & Roland, 1984
Possible association with malignancies; autoantibodies reacting with antigens in centrosomes are frequently found in sera of patients with breast cancer
Madrid et al., 2015Maroun et al., 2014
Autoantibodies to ?-enolase, ?-enolase, Mob1, PCM-1/2, and pericentrin have been described in children with cerebellar ataxia after varicella infection; one patient with hyperthyroidism and vague muscle pain and one patient with Raynaud’s phenomenon, both without evidence of a SARD, had antibodies to ?-enolase and ?-enolase
Fritzler et al., 2003Rattner et al., 1991
With respect to autoantibodies to ninein and Cep-250, there is no apparent correlation between serum autoantibody reactivity and the clinical diagnosis; reported in RA and SLE
Mack et al., 1998Howng et al., 2011
Most reports describe autoantibodies directly binding to specific antigens (i.e., antigen-specific immunoassays) and do not actually show correlations with the AC-24 pattern as such; specific immunoassays for these autoantibodies are currently not commercially available.
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The AC-25 pattern has low positive predictive value for any disease
Mozo et al., 2008
Found very infrequently in a routine serology diagnostic setting
Mozo et al., 2008
Antigen recognized includes HsEg5; specific immunoassays for this autoantibody, or other spindle fiber targets, are currently not commercially available
Whitehead et al., 1996Szalat et al., 2010
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While AC-25 is not associated with a defined autoimmune disease, reactivity with HsEg5 is more commonly found in SjS and SLE Note: Specific immunoassays for HsEg5 are currently not commercially available.
Whitehead et al., 1996Szalat et al., 2010
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Approximately one-half of the patients with the AC-26 pattern have clinical features of a SARD (SjS, SLE, UCTD, limited SSc, or RA); the AC-26 pattern is also observed in patients with organ-specific autoimmune diseases and less frequently in non-autoimmune conditions, especially when in low titer
Mozo et al., 2008Szalat et al., 2010Grypiotis et al., 2002Price, McCarty & Pettijohn, 1984Bonaci-Nikolic et al., 2006
Found very infrequently in a routine serology diagnostic setting
Mozo et al., 2008
Antigens recognized include NuMA, centrophilin, SP-H antigen and NMP-22; specific immunoassays for these autoantibodies are currently not commercially available
Compton, Szilak & Cleveland, 1992
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The AC-27 pattern has low positive predictive value for any disease
Rattner, Mack & Fritzler, 1998
Found very infrequently in a routine serology diagnostic setting
Vermeersch et al., 2013
Antigens recognized include, among other, CENP-E, CENP-F, TD60, MSA36, KIF-14, MKLP-1, MPP1/ KIF20B, and INCENP; specific immunoassays for these autoantibodies are currently not commercially available
Rattner, Mack & Fritzler, 1998Humbel RLConrad, 2013Rodríguez-Bayona et al., 2007
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Incidentally described in patients with SSc, Raynaud’s phenomenon, and malignancy
Fritzler et al., 1987Tausche et al., 2005Vermeersch & Bossuyt, 2013
Autoantibodies to CENP-E, CENP-F, TD60, MSA36, KIF-14, and MKLP-1 have been described in patients with SSc (limited and diffuse), SLE, and malignancies
Rattner, Mack & Fritzler, 1998Humbel, 2013
Autoantibodies to INCENP have been described in a single patient with Graham-Little-Piccardi-Lasseur Syndrome
Rodriguez-Bayona et al., 2007
Autoantibodies to MPP1 /KIF20B (M-phase phosphoprotein 1) have been described in patients with idiopathic ataxia, other neurological syndromes and paroxysmal nocturnal haemoglobinuria
Fritzler et al., 2000Alahmad et al., 2010
Most reports describe autoantibodies directly binding to specific antigens (i.e., antigen-specific immunossays) and do not actually show correlations with the AC-27 pattern as such; specific immunoassays for these autoantibodies are currently not commercially available.
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The AC-28 pattern has low positive predictive value for any disease
Found very infrequently in a routine serology diagnostic setting
Gitlits et al., 2000
Antigens recognized include DCA, MCA1, and MCA5; specific immunoassays for these autoantibodies are currently not commercially available
Gitlits et al., 2000Blaschek et al., 1993Rayzman & Sentry, 2006
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Autoantibodies to DCA have been described in patients with SLE
Blaschek, Muller & Youinou, 1993
Autoantibodies to MCA1 have been described in patients with carcinoma
Rayzman & Sentry, 2006
Autoantibodies to MCA5 have been described in patients with discoid lupus erythematosus, chronic lymphocytic leukemia, SjS, and polymyalgia rheumatica
Gitlits et al., 2000
Specific immunoassays for these autoantibodies are currently not commercially available.
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The AC-29 pattern is highly specific for SSc, in particular with diffuse cutaneous SSc and more aggressive forms of SSc
Andrade et al., 2018Dellavance et al., 2009Johnson et al., 2012
If SSc is clinically suspected, it is recommended to perform a follow-up test for anti-Topoisomerase I (formerly Scl-70) antibodies; the anti-Topoisomerase I antibodies are included in the classification criteria for SSc and the antigen is included in routine ENA profiles
van den Hoogen et al, 2013Johnson et al., 2012Basu & Reveille, 2005
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Esclerose Sistêmica com tendência a comprometimento visceral grave; associação com neoplasia subjacente.
Dellavance, Gabriel Júnior, Nuccitelli Barbara, et al., 2009.Reimer G, Raska I, Tan EM, Scheer U., 1987
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Superposição Esclerose Sistêmica/ Polimiosite, Lúpus Eritematosos Sistêmico e Esclerose Sistêmica.
Betteridge Z & McHugh N., 2016 Dellavance, Gabriel Júnior, Cintra et al., 2003 Francoeur AM, Peebles CL, Gompper PT, Tan EM. 1986Franceschini F, Cavazzana I, Generali D., 2002 Ho KT, Reveille JD., 2003Takeda Y, Dynan WS, 2001
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Necessita investigação porque esse padrão pode estar relacionado a doenças reumáticas sistêmicas autoimunes (DRAI). No entanto, a associação com as DRAI é bem mais fraca que aquela observada com o padrão nuclear homogêneo.
Franca NR, Dellavance, A Rodrigues SH., 2011Mariz HA, Sato EI, Barbosa SH, et al., 2011.Francescantonio, Cruvinel, Dellavance et al. 2014.
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Em si, este padrão representa fraca evidência de autoimunidade sistêmica; entretanto, deve-se investigar DRAI de acordo com a apresentação clínica de cada paciente.
Cruvinel, Andrade, von Mühlen et al., 2019
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Em pacientes com lupus, os anticorpos anti-rRNP estão associados a envolvimento do SNC, envolvimento hepático e glomerulonefrite classe V; em alguns pacientes, os títulos podem flutuar conforme a atividade da doença.
Bonfa E, Golombek SJ, Kaufman LD, et al: Association between lupus psychosis and anti-ribosomal P protein antibodies. N Engl J Med 317:265-71, 1987. Isshi K, Hirohata S: Differential roles of the anti-ribosomal P antibody and antineuronal antibody in the pathogenesis of central nervous system involvement in systemic lupus erythematosus. Arthritis Rheum 41:1819-27, 1998.