Publisher Summary In l961, Beck reported that the sera of patients with rheumatic diseases contained antibodies to nucleolar structures, and further studies in the 1970s showed that such anti-nucleolar antibodies (ANoA) were more frequent in patients with scleroderma. A nucleolar immunofluorescence pattern described as “clumpy” was shown to be because of antibodies to a 34 kDa nucleolar protein named fibrillarin because of its localization to the dense fibrillar and fibrillar center regions of the nucleolus. Fibrillarin, together with a number of other proteins, is a constituent of box C/D snoRNA–protein complexes called small nucleolar ribonucleoprotein (snoRNP) particles. Fibrillarin is thought to be an S-adenosylmethionine-dependent methyltransferase that catalyzes site-specific ribose methylation of ribosomal RNA. Given the potential antigenic complexity of snoRNPs, it is proposed that the abbreviation AFA (anti-fibrillarin antibody) be used when denoting the use of detection assays that use fibrillarin as a pure antigen. Nomenclature that uses snoRNP/RNA terminology (anti-U3, anti-box C/D) should not be used as surrogates for AFA. Although AFA occur in less than 15% of patients with systemic sclerosis (SSc or scleroderma), they are highly associated with diffuse cutaneous SSc. AFA have been found more frequently in SSc patients of African rather than Caucasian descent, in males than in females, and in patients with internal organ involvement, including pulmonary hypertension, myositis, and renal disease.