AC-21 - Cytoplasmic reticular/AMA
Previous Nomenclature mitochondria-like
Description Coarse granular filamentous staining extending throughout the cytoplasm. e.g. anti-mitochondrial antibodies.
Antigen Association PDC-E2/M2, BCOADC-E2, OGDC-E2, E1α subunit of PDC, E3BP/protein X
Clinical Relevance
First level information
About Clinical Relevance & List of Abbreviations

Commonly found in PBC, but also detected in SSc, including PBC-SSc overlap syndrome and PBC-SjS overlap syndrome (93–97)

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 (93, 94)

Additional antigens recognized include the E1α and E1β 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*) (93, 94)


*Availability of the inflammatory myopathy profile, the SSc profile and the (extended) liver profile may be limited to specialty clinical laboratories.

First level information references
European Association for the Study of the Liver. EASL clinical practice guidelines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol 2017;67:145-72.
Shuai Z, Wang J, Badamagunta M, et al. The fingerprint of antimitochondrial antibodies and the etiology of primary biliary cholangitis. Hepatology 2017;65:1670-82.
Skare TL, Nisihara RM, Haider O, et al. Liver autoantibodies in patients with scleroderma. Clin Rheumatol 2011;30:129-32.
Zheng B, Vincent C, Fritzler MJ, et al. Prevalence of systemic sclerosis in primary biliary cholangitis using the new ACR/EULAR classification criteria. J Rheumatol 2017;44:33-9.
Nardi N, Brito-Zerón P, Ramos-Casals M, et al. Circulating auto-antibodies against nuclear and non-nuclear antigens in primary Sjögren´s syndrome: prevalence and clinical significance in 335 patients. Clin Rheumatol 2006;25:341-6.
Second level information
Second level information references
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?
Online since 19 May 2015