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| Previous Nomenclature | GW bodies, processing bodies, endosomes, lysosomes |
| Description | Discrete dots in the cytoplasm |
| Antigen Association | GW bodies are generally spherical bodies in the cytoplasm of interphase cells with higher numbers in late S/G2 cells involved in mRNA processing. In electron microscopy the structures are electron dense and devoid of a limiting membrane. By comparison, endosomes and lysosomes are membrane bound organelles. Endosomes are involved in phagocytosis and export of proteins from the Golgi complex while lysosomes contain digestive enzymes capable of breaking down proteins, nucleic acids, carbohydrates, and lipids. GW body associated antigens: GW182, Su/Ago2, Ge-1/human enhancer of decapping large subunit (Hedls) [1, 2]. ▶ Endosome associated antigens: early endosome antigen 1 (EEA-1), cytoplasmic linker protein 170 (CLIP-170), glutamate receptor interacting protein (GRIP)-associated protein-1 (GRASP-1/GRIPAP), lysobisphosphatidic acid-1 [1]. ▶ Lysosome associated antigen: autophagic protein microtubule-associated light-chain 3 (LC3) [3]; lysosome-associated membrane proteins (LAMPs) antibodies have been described particularly to LAMP2 but there is no evidence that they produce the AC-18 pattern [4-6]. ▶ Specific immunoassays for these autoantibodies are currently not commercially available. Notes: Autoantibodies to GW-bodies, endosomes, and lysosomes may yield slightly different HEp-2 IFA patterns [1, 2]. |
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Clinical Relevance
First level information About Clinical Relevance & List of Abbreviations |
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▶ Autoantibodies associated with the AC-18 pattern have been reported in systemic autoimmune rheumatic diseases and in a variety of other diseases including cancers [2, 7]; their prevalence in unselected or specified disease cohorts has not been thoroughly studied. |
| Second level information |
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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 systemic lupus erythematosus (SLE), rheumatoid arthritis, and primary biliary cholangitis (PBC) [2]. ▶ Analysis by ALBIA and immunoprecipitation of recombinant proteins indicated that autoantibodies were directed against Ge-1/Hedls (58%), GW182 (40%), and Su/Ago2 (16%) [2, 8, 9]. Autoantibodies to endosomal components: ▶ Autoantibodies to EEA1 were seen in a variety of conditions, but ~40% of the patients had a neurological disease [1]. ▶ Autoantibodies to CLIP-170 were reported in 4 patients with different diseases including the prototype patient with SLE and idiopathic inflammatory myopathies; the remaining 3 patients had limited cutaneous systemic sclerosis, glioblastoma, and idiopathic pleural effusion [10]. ▶ Autoantibodies to both LBPA and GRASP-1 have not been studied thoroughly in unselected or specified disease cohorts; autoantibodies to GRASP-1 were detected in 17% of PBC sera [11, 12]. Autoantibodies to lysosomal component: ▶ LC3 autoantibodies were reported in a case of SLE [3]. ▶ LAMP-2 autoantibodies were reported in anti-neutrophil cytoplasmic antibodies-related vasculopathies [4-6]. Notes: Most reports describing autoantibodies directly binding to specific endosomal and lysosomal antigens do not show correlations with the AC-18 pattern as such. |
| References |
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1. 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. 2. Bhanji RA, Eystathioy T, Chan EKL, Bloch DB, Fritzler MJ. Clinical and serological features of patients with autoantibodies to GW/P bodies. Clin Immunol. 2007;125:247-56. 3. Maellaro E, Terzuoli L, Bacarelli MR, Del Bello B, Bizzaro N, Porcelli B. Autoantibodies against the autophagic protein microtubule-associated light-chain 3 (LC3): Immunocharacterization of an atypical ANA pattern. Autoimmunity. 2020;53:245-52. 4. Kain R, Tadema H, McKinney EF, Benharkou A, Brandes R, Peschel A, Hubert V, Feenstra T, et al. High prevalence of autoantibodies to hLAMP-2 in anti-neutrophil cytoplasmic antibody-associated vasculitis. J Am Soc Nephrol. 2012;23:556-66. 5. Akbaba TH, Toor KK, Mann SK, Gibson KM, Alfaro GA, Balci-Peynircioglu B, Cabral DA, Morishita KA, et al. Anti-LAMP-2 Antibody Seropositivity in Children with Primary Systemic Vasculitis Affecting Medium- and Large-Sized Vessels. Int J Mol Sci. 2024;25. 6. Gibson KM, Kain R, Luqmani RA, Ross CJ, Cabral DA, Brown KL. Autoantibodies Against Lysosome Associated Membrane Protein-2 (LAMP-2) in Pediatric Chronic Primary Systemic Vasculitis. Front Immunol. 2020;11:624758. 7. Hsiao CY, Su LJ, Yu KH, Chan TM. Clinical significance of cytoplasmic discrete dots (AC-18) patterns in HEp-2 cell indirect Immunofluorescence: insights from a Taiwanese multicenter study. Clin Chim Acta. 2025;578:120521. 8. Yu JH, Yang WH, Gulick T, Bloch KD, Bloch DB. Ge-1 is a central component of the mammalian cytoplasmic mRNA processing body. RNA. 2005;11:1795-802. 9. Bloch DB, Yu JH, Yang WH, Graeme-Cook F, Lindor KD, Viswanathan A, Bloch KD, Nakajima A. The cytoplasmic dot staining pattern is detected in a subgroup of patients with primary biliary cirrhosis. J Rheumatol. 2005;32:477-83. 10. Griffith KJ, Ryan JP, Senécal JL, Fritzler MJ. The cytoplasmic linker protein CLIP-170 is a human autoantigen. Clin Exp Immunol. 2002;127:533-8. 11. Stinton LM, Selak S, Fritzler MJ. Identification of GRASP-1 as a novel 97 kDa autoantigen localized to endosomes. Clin Immunol. 2005;116:108-17. 12. Stinton LM, Swain M, Myers RP, Shaheen AA, Fritzler MJ. Autoantibodies to GW bodies and other autoantigens in primary biliary cirrhosis. Clin Exp Immunol. 2011;163:147-56. |
| FAQ |
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Reporting AC-18 - does it change with the 2021 classification chart revision? Question: I have one question for the new classification tree. As AC-18 was removed from the category of cytoplasmic speckled and assigned still at the expert level. If the lab only reports competent-level patterns, how should AC-18 be reported? Should they just report the first branch of the classification tree as "cytoplasmic"? |