AC-9 - Clumpy nucleolar
Previous Nomenclature None
Description Irregular staining of the nucleoli and Cajal bodies with a peri-chromosomal staining at the metaphase plates. e.g. anti-fibrillarin.
Antigen Association U3-snoRNP/fibrillarin
Clinical Relevance
First level information
About Clinical Relevance & List of Abbreviations

Found in patients with SSc (48)

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*) (48)

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 (23, 48–50)

Among SSc patients, anti-U3RNP/fibrillarin antibodies are most commonly found in African American and Latin American patients (48, 49, 51)


Notes: Although some anti-U3RNP/fibrillarin immunoassays are commercially available, technical issues relating to the limited sensitivity of these immunoassays should be taken into consideration (24).


*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
Johnson SR, Fransen J, Khanna D, et al. Validation of potential classification criteria for systemic sclerosis. Arthritis Care Res 2012;64:358-67.
Mehra S, Walker J, Patterson K, et al. Autoantibodies in systemic sclerosis. Autoimmun Rev 2013;12:340-54.
Okano Y, Steen VD, Medsger TA. Autoantibody to U3 nucleolar ribonucleoprotein (fibrillarin) in patients with systemic sclerosis. Arthritis Rheum 1992;35:95-100.
Arnett FC, Reveille JD, Goldstein R, et al. Autoantibodies to fibrillarin in systemic sclerosis (scleroderma). An immunogenetic, serologic, and clinical analysis. Arthritis Rheum 1996;39:1151-60.
Tormey VJ, Bunn CC, Denton CP, et al. Anti-fibrillarin antibodies in systemic sclerosis. Rheumatology 2001;40:1157-62.
Nandiwada SL, Peterson LK, Mayes MD, et al. Ethnic differences in autoantibody diversity and hierarchy: More clues from a US cohort of patients with systemic sclerosis. J Rheumatol 2016;43:1816-24.
Second level information
Second level information references
Discrepancy in HEp-2 IFA and western blot data. How do you explain the detection of antibodies by western blot (WB) that are not related to the pattern observed in HEp-2 cells by indirect immunofluorescence (IFA)? 
Online since 19 May 2015