ANA Patterns

AC-18 - Cytoplasmic discrete dots/GW body-like


Previous Nomenclature	GW body, processing body, lysosome*
Description	Staining of GW bodies in the cytoplasm of interphase cells with high numbers in late S/G2 cells. e.g. anti-GW182, anti-Su/Ago2.
Antigen Association	GW182, Su/Ago2, *no molecular evidence to support this pattern is associated with lysosomal targets

Clinical Relevance
First level information
About Clinical Relevance & List of Abbreviations

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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 (84)

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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

Notes: Autoantibodies to GW-bodies and endosomes may yield slightly different HEp-2 IIFA patterns (84, 85).

First level information references

84.

Bhanji RA, Eystathioy T, Chan EK, et al. Clinical and serological features of patients with autoantibodies to GW/P bodies. Clin Immunol 2007;125:247-56.

85.

Stinton LM, Eystathioy T, Selak S, et al. 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.

Second level information

Autoantibodies to GW bodies:

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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 (28)

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Analysis by ALBIA and immunoprecipitation of recombinant proteins indicated that autoantibodies were directed against Ge-1/Hedls (58%), GW182 (40%), and Su/Ago2 (16%) (28)

Autoantibodies to endosomal components:

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Autoantibodies to EEA1 were seen in a variety of conditions, but ~40% of the patients had a neurological disease (29)

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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 (30)

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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 (31, 32)

Notes: 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.

Second level information references

28.

Bhanji RA, Eystathioy T, Chan EKL, et al. Clinical and serological features of patients with autoantibodies to GW/P bodies. Clin Immunol 2007;125:247-56.

29.

30.

Griffith KJ, Ryan JP, Senecal JL, et al. The cytoplasmic linker protein CLIP-170 is a human autoantigen. Clin Exp Immunol 2002;127:533-8.

31.

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.

32.

Stinton LM, Swain M, Myers RP, et al. Autoantibodies to GW bodies and other autoantigens in primary biliary cirrhosis. Clin Exp Immunol 2011;163:147-56.

FAQ

How to deal with just a “nuclear speckled” IFA report?

In my practice I have followed patients with ANA findings, with a nuclear speckled pattern (without specifying whether fine/dense/coarse), in patients with very heterogeneous phenotypes, some with a clinical picture that suggests further investigation of systemic autoimmune disease (one patient with proximal muscle weakness and skin thickening) and others who represent only non-specific findings. In such situations, as a precaution, I request more specific autoantibodies. However, this pattern (nuclear speckled pattern) is not described by the "ICAP" and I am in doubt about which antigenic association it represents, even to guide which autoantibody may be present and which ones to look after. How to interpret this pattern? Does the lab describe it when it is not possible to "refine" such a conclusion? Could this be associated with deficiency in the methodology, sample, interpretation?

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"?