Anti-Sitoplazmik ve Anti-Mitotik Otoantikorlar; Bu Antikorların Hastalıklarla İlişkisi Var Mı?
Yıl 2022,
, 851 - 861, 28.11.2022
Nilgün Kaşifoğlu
,
Nazife Şule Yaşar Bilge
,
Timuçin Kaşifoğlu
Öz
Sistemik otoimmün hastalıkların tanısında antinükleer antikor (ANA) incelemesi yapılır ve HEp-2 hücrelerini kullanan indirekt immünfloresan (IIF) test altın standart yöntemdir. HEp-2, çok sayıda hedef antijene yönelmiş otoantikorların saptanmasına imkân verir. “Antinükleer Antikor (ANA) Paterninde Uluslararası Uzlaşı” rehberi, paternleri üç gruba ayırır: nükleer, sitoplazmik ve mitotik. Bunların çoğu otoimmün hastalıklarla ilişkilidir, ancak bazıları otoimmün hastalıklarda nadiren görülür veya otoimmün hastalık dışındaki durumlarla ilişkili olabilir. Sitoplazmik ve mitotik paternlerin nasıl raporlanacağı konusunda- negatif veya pozitif- bir fikir birliği yoktur. IIF ile ANA değerlendirmesinde sitoplazmik veya mitotik boyanma olan hastaların özelliklerini incelemeyi amaçladık. Tıbbi Mikrobiyoloji Laboratuvarımızda 01.01.2015-31.12.2019 tarihleri arasında 16940 hastaya ait 18985 ANA testi çalışılmıştır. 385 hastaya ait 393 (%2.07) testte sitoplazmik veya mitotik patern tespit edildi. Anti-mitokondriyal antikor (AMA), anti-düz kas antikoru (ASMA), anti-Jo-1 ve anti-ribozomal P-proteini düşündüren sitoplazmik paternler çalışmaya dahil edilmedi. En sık görülen paternler anti-midbody (hücreler arası köprü), anti-spindle fibers (iğsi iplikçikler) ve anti-vimentin paternleriydi. Altmış altı romatoloji hastasında ANA negatifti ancak sitoplazmik veya mitotik boyanma saptandı. Bu hastaların tanı ve paternleri arasında istatistiksel olarak anlamlı bir fark bulunamadı. Anti-hücre antikoru terimi kullanılmadıkça, sitoplazmik veya mitotik patern olması durumunda ANA'nın “negatif” olarak rapor edilmesini öneriyoruz. Bu boyanma, önemli sitoplazmik paternleri ayırt etmek ve bazı spesifik durumlar hakkında fikir vermek için raporun açıklama kısmında belirtilmelidir
Kaynakça
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The Anti-Cytoplasmic and Anti-Mitotic Autoantibodies; Are These Antibodies Associated with Diseases?
Yıl 2022,
, 851 - 861, 28.11.2022
Nilgün Kaşifoğlu
,
Nazife Şule Yaşar Bilge
,
Timuçin Kaşifoğlu
Öz
Examination of antinuclear antibody (ANA) is used in diagnosis of systemic autoimmune diseases, and the indirect immunofluorescence (IIF) assay using HEp-2 cells is the gold standard method. HEp-2 allows the detection of multiple target antigen-directed autoantibodies. The guide “The International Consensus on ANA Patterns (ICAP)”, characterizes the patterns into three groups: nuclear, cytoplasmic, and mitotic. The majority of these are associated with autoimmune diseases, but some are rarely seen in autoimmune diseases or may be associated with conditions other than autoimmune disease. There is no consensus on how to report cytoplasmic and mitotic patterns-negative or positive. We aimed to examine the characteristics of patients that had cytoplasmic or mitotic staining in ANA evaluation by IIF. In our Medical Microbiology Laboratory, 18985 ANA tests of 16940 patients were studied between 01.01.2015-31.12.2019. Cytoplasmic or mitotic pattern was detected in 393 (2.07%) tests belonging to 385 patients. Cytoplasmic patterns suggestive of anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (ASMA), anti-Jo-1 and anti-ribosomal P-protein were not included. The most common patterns were anti-midbody, anti-spindle fibers, and anti-vimentin patterns. There were 66 rheumatology patients that were negative for ANA but had cytoplasmic or mitotic staining. There was no statistically significant difference between the diagnosis and patterns of these patients. We suggest that the ANA should be reported as “negative” in case of cytoplasmic or mitotic pattern unless the term anti-cell antibody is used. It should be noted in the description part of the report in order to distinguish significant cytoplasmic patterns and give an idea for some specific conditions.
Kaynakça
- Meroni PL, Schur PH. ANA screening: an old test with new recommendations. Ann Rheum Dis 2010;69:1420-2.
- Chan EKL, de Melo Cruvinel W, Andrade LEC. The International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns (ICAP) initiative - Current state and perspectives. In: Conrad K, Chan EKL, Andrade LEC, Steiner G, Pruijn GJM, Shoenfeld Y, editors. From Autoantibody Research to Standardized Diagnostic Assays in the Management of Human Diseases series. Report on the 12th Dresden Symposium on Autoantibodies. Germany. 2015. p. 282-288.
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- Agmon-Levin N, Damoiseaux J, Kallenberg C, Sack U, Witte T, Herold M, et al. International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies. Ann Rheum Dis 2014;73:17-23.
- Chan EKL, Damoiseaux J, Carballo OG, Conrad K, de Melo Cruvinel W, Francescantonio PLC, et al. Report of the First International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns 2014-2015. Front Immunol 2015;6:412.
- Andrade LEC, Klotz W, Herold M, Conrad K, Rönnelid J, Fritzler MJ, von Mühlen CA, Satoh M, Damoiseaux J, Cruvinel WM, Chan EKL; Executive Committee of ICAP. International consensus on antinuclear antibody patterns: definition of the AC-29 pattern associated with antibodies to DNA topoisomerase I. Clin Chem Lab Med 2018. pii: /j/cclm.ahead-of-print/cclm-2018-0188/cclm-2018-0188.xml.
- Chan EKL, Damoiseaux J, de Melo Cruvinel W, Carballo OG, Conrad K, Francescantonio PL, et al. Report on the second International Consensus on ANA Pattern (ICAP) workshop in Dresden 2015. Lupus 2016;25:797-804.
- Hughes GRV, Asherson RA. Atypical lupus with special reference to ANA negative lupus and lupus subsets. Adv Nephrol 1985;14:333-46.
- Reichlin M. ANA negative systemic lupus erythematosus sera revisited serologically. Lupus 2000; 9:116-9.
- Dellavance A, Junior AG, Cintra AFU, Ximenes AC, Nuccitelli B, Taliberti BH, et al. II Brazilian consensus on antinuclear antibodies in HEp-2 cells. Definitions for standardization of autoantibody testing against the nucleus (ANA HEP-2), nucleolus, cytoplasm and mitotic apparatus, as well as its clinical associations. Rev Bras Reumatol 2003;43:129-40.
- von Mühlen CA, Garcia-De La Torre I, Infantino M, Damoiseaux J, Andrade LEC, Carballo OG, Conrad K, Francescantonio PLC, Fritzler MJ, Herold M, Klotz W, de Melo Cruvinel W, Mimori T, Satoh M, Musset L, Chan EKL. How to report the antinuclear antibodies (anti-cell antibodies) test on HEp-2 cells: guidelines from the ICAP initiative. Immunol Res 2021 Dec;69(6):594-608.
- Francescantonio P, Cruvinel W, Dellavance A, et al. IV Brazilian Guidelines for autoantibodies on HEp-2 cells. Rev Bras Reumatol 2014;54(1):44–50.
- Infantino M, Palterer B, Biagiotti R, Almerigogna F, Benucci M, Damiani A, et al. Reflex testing of speckled cytoplasmic patterns observed in routine ANA HEp-2 indirect immunofluorescence with a multiplex anti-synthetase dot-blot assay: a multicentric pilot study. Immunol Res 2018;66:74‐8.
- Stinton LM, Eystathioy T, Selak S, Chan EKL, Fritzler MJ. Autoantibodies to protein transport and messenger RNA processing pathways: endosomes, lysosomes, Golgi complex, proteasomes, assemblyosomes, exosomes, and GW bodies. Clin Immunol 2004;110:30-44.
- Koh WH, Dunphy J, Whyte J, Dixey J, McHugh NJ. Characterization of anticytoplasmic antibodies and their clinical associations. Ann Rheum Dis 1995;54:269-73.
- Craig WY, Ledue TB, Collins MF, Meggison WE, Leavitt LF, Ritchie RF. Serologic associations of anti-cytoplasmic antibodies identified during anti-nuclear antibody testing. Clin Chem Lab Med 2006;44:1283-6.
- Satoh M, Chan EKL, Ho LA, Rose KM, Parks CG, Cohn RD, et al. Prevalence and sociodemographic correlates of antinuclear antibodies in the United States. Arthritis Rheum 2012;64:2319-27.
- Betancur JF, Londoño A, Estrada VE, Puerta SL, Osorno SM, Loazia A, et al. Uncommon patterns of antinuclear antibodies recognizing mitotic spindle apparatus antigens and clinical associations. Medicine (Baltimore) 2018;97:e11727.
- Vermeersch P, Bossuyt X. Prevalence and clinical significance of rare antinuclear antibody patterns. Autoimmun Rev 2013;12:998-1003.
- Senecal JL, Oliver JM, Rothfield N. Anticytoskeletal autoantibodies in the connective tissue diseases. Arthritis Rheum 1985;28:889-98.
- Fritzler MJ, Ayer LM, Gohill J, O’Connor C, Laxer RM, Humbel RL. An antigen in metaphase chromatin and the midbody of mammalian cells binds to scleroderma sera. J Rheumatol 1987;14:291-4.
- Bettoni L, Perini P, Milanesi B. Significato clinic degli anticorpi anti-midbody. (In Italian). Caso Clinico RIMeL / IJLaM 2009; 5.
- Tausche AK, Conrad K, Seidel W, Roch B. Anti-midbody antibodies as a possible predictive factor for a special limited or abortive form of systemic sclerosis? Ann Rheum Dis 2005;64:1237-8.
- Andrade LE, Chan EK, Peebles CL, Tan EM. Two major autoantigen-antibody systems of the mitotic spindle apparatus. Arthritis Rheum 1996;39:1643-53.
- Whitehead CM, Winkfein RJ, Fritzler MJ, Rattner JB. The spindle kinesin-like protein HsEg5 is an autoantigen in systemic lupus erythematosus. Arthritis Rheum 1996;39:1635-42.
- Mozo L, Gutiérrez C, Gómez J. Antibodies to mitotic spindle apparatus: clinical significance of NuMA and HsEg5 autoantibodies. J Clin Immunol 2008;28:285-90.
- Szalat R, Ghillani-Dalbin P, Jallouli M, Amoura Z, Musset L, Cacoub P, Sene D. Anti-NuMA1 and anti-NuMA2 (anti-HsEg5) antibodies: Clinical and immunological features: A propos of 40 new cases and review of the literature. Autoimmun Rev 2010;9:652-6.
- Rose ML. Role of anti-vimentin antibodies in allograft rejection. Hum Immunol 2013;74:1459-62.
- Divanyan T, Acosta E, Patel D, Constantino D, Lopez-Soler RI. Anti-vimentin antibodies in transplant and disease. Hum Immunol 2019;80:602-7.
- Alvarez-Márquez A, Aguilera I, Blanco RM, Pascual D, Encarnacion-Carrizosa M, Alvarez-Lopez MR, et al. Positive association of anticytoskeletal endothelial cell antibodies and cardiac allograft rejection. Hum Immunol 2008;69:143-8.
- Lopez-Soler RI, Borgia JA, Kanangat S, Fhied CL, Conti DJ, Constantino D, et al. Anti-vimentin Antibodies Present at the Time of Transplantation May Predict Early Development of Interstitial Fibrosis/Tubular Atrophy. Transplant Proc 2016;48:2023-33.
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