Anti-centromere antibodies in a patient with anti-Jo-1 anti-synthetase syndrome

Dear Editor, A 54-year-old female had polyarthritis for 3 years, breathlessness for 2 years, and symmetrical proximal muscle weakness for 6 months. Examination revealed roughened and hyperkeratotic skin over the radial aspect of right index and middle finger, suggestive of mechanic's hand (MH) [Figure 1a]. Creatine phosphokinase was elevated four times above normal limit, and computed tomography findings of the chest were suggestive of interstitial lung disease (ILD). Anti-nuclear antibodies on Hep-2 cells at 1:100 titre demonstrated staining of the centromeres, nucleus and cytoplasm, suggestive of a mixed pattern [Figure 1b]. Line immunoassay detected anti-centromere antibodies (ACA) (2+), anti-Ro-52 antibodies (1+), and anti-Jo-1 antibodies (3+). Presence of ACA was also confirmed by enzyme-linked immunosorbent assay. Although arthritis, ILD and myositis in the presence of these antibodies, could be the manifestations of either anti-synthetase syndrome (ASS) or systemic sclerosis (SSc), presence of MH and absence of SSc/CREST syndrome (Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia) specific manifestations supported the diagnosis of ASS. Patient also satisfied the Connors criteria for ASS.[1]Figure 1: (a) Mechanic's hand: Radial aspect of the right index and middle finger showing hyperkeratotic and roughened skin (arrows). (b) Anti - nuclear antibodies on Hep - 2 cells at 1:100 titre showing fine speckled cytoplasmic staining (black arrow) along with centromere pattern (40 - 60 discrete dots in the nuclei of interphase cells (white arrow), and a bar of closely associated speckles in the chromosomal plate of mitotic cells (arrowhead), with a background fine speckled nuclear staining)Anti-centromere antibodies (ACA) are specific for limited cutaneous SSc, and has specificity of 96--100% in distinguishing SSc from other connective tissue diseases.[2] ACA have been rarely reported in patients with primary biliary cirrhosis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, polymyositis and dermatomyositis.[3] Although SSc is the most common overlap connective tissue disease in patients with idiopathic inflammatory myositis with a prevalence of 4.4--7.7%,[4] we found only two published reports of co-existing ACA and anti-Jo-1 antibodies.[3,5] ACA (without SSc specific clinical features) in patients with ASS are extremely unusual, and its presence should warrant vigilance for development of SSc specific manifestations in these patients. In the present case, the mixture of centromere, nuclear and cytoplasmic patterns of ANA, an extremely unusual combination, co-related well with presence of ACA, anti-Ro-52, and anti-Jo-1 antibodies. Thus, proper interpretation of various ANA patterns on Hep-2 cells is of crucial importance for guiding the treating physicians on further workup and appropriate management of autoimmune diseases. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.