Background/Aims Anti-synthetase syndrome (ASS) represents a distinct entity within myositis spectrum disorders; however, correct classification of patients with anti-tRNA synthetase autoantibodies and skin manifestations akin to dermatomyositis (DM) remains uncertain. Our aim was to compare clinical characteristics, skin involvement, and malignancy, between patients with ASS and DM, classified by disease-specific autoantibodies. Methods Data from 05/2009-03/2016 from 9 countries from the prospective, myositis EuroMyositis registry were downloaded. Those with anti-tRNA synthetase autoantibodies (Jo-1/PL-7/PL-12/OJ/EJ/KS) were classified as ASS, and those with Mi-2/TIF1-γ/NXP2/SAE/MDA5 autoantibodies as DM. Clinical phenotypes including malignancies (except skin malignancies) were tabulated. Characteristics of patients with skin involvement (excluding mechanic’s hands and Raynaud’s phenomenon) were compared using Fisher’s exact test with Bonferroni corrected p-values. Results Of 3,067 patients, 2,028 had autoantibody profiling results (66.1%), of which 783 (38.6%) were positive for at least one of the autoantibodies being considered. Five patients with dual autoantibody specificities were excluded. Of the remaining 778, 320 (41.1%) were classified as DM, and 458 (58.9%) as ASS. Median age at diagnosis was 48.2 years (interquartile range [IQR] 37.5 to 57.8) in the DM cohort and 49 (IQR 38.3 to 62.2) in the ASS cohort. Skin involvement was present in 277 (86.6%) DM patients (DM skin) vs 204 (44.5%) ASS patients (ASS skin) (pcorr<0.01) (Table 1). Whilst relatively high proportions of so-called “DM-specific” rashes were seen in ASS skin, the frequency of heliotrope rash, Gottron’s papules, violaceous rash, periorbital rash, V-sign, shawl sign, and periungual erythema was significantly higher in DM skin (pcorr<0.01 for all). Conversely, mechanic’s hands, Raynaud’s, arthritis, and interstitial lung disease were more frequent in ASS skin (pcorr<0.01 for all). Malignancy was less frequent in ASS skin vs DM skin (pcorr<0.01) and occurred temporally closer to myositis diagnosis in DM skin (median 0.95 months [IQR -6.54. to 19.45]) vs ASS skin (median 12.17 months [IQR -15.85 to 79.31]). Conclusion Patients with ASS have frequent skin involvement but also a distinct clinical phenotype compared to DM. These findings may inform the development of future classification criteria for ASS. Disclosure R.M. Hum: None. J.B. Lilleker: None. J.A. Lamb: None. W.E. Ollier: None. G. Wang: None. L.R. Wedderburn: None. L.P. Diederichsen: None. J. Schmidt: None. P. Oakley: None. O. Benveniste: None. M.G. Danieli: None. K. Danko: None. N.T.P. Thuy: None. M.V.D. Mercado: None. H. Andersson: None. B.D. Paepe: None. J.L.D. Bleecker: None. B. Maurer: None. L.J. McCann: None. N. Pipitone: None. N. McHugh: None. P. New: None. J. Vencovsky: None. I.E. Lundberg: None. H. Chinoy: None.
SUMMARY In vitro functions of polymorphonuclear (PMN) neutrophils were studied in 20 patients with progressive systemic sclerosis (PSS). An increase in the basal chemiluminescence (CL) activity of peripheral blood PMNs was found, suggesting that these cells had been preactivated in vivo. Patients with more extensive skin disease or signs of disease progression tended to have higher basal CL values. Active oxygen products during the respiratory burst may increase the extent of inflammatory and fibrotic processes and could be involved in the endothelial injury in PSS. The stimulatory capacity of CL response was normal in our study. No alterations were found in the opsonised yeast phagocytic activity of granulocytes when compared with control values. The binding of erythrocyte-antibody particles was found also to be normal. A depressed chemotactic activity of PMN cells against zymosan activated serum was also shown. The cause of the decreased chemotaxis of PMNs remains to be elucidated.
This work was undertaken to further define the antigen-presenting capabilities of thyroid epithelial cells, as this is of paramount importance with regard to their potential to trigger autoimmune thyroiditis. For this purpose we developed the murine cloned thyroid-derived epithelial cell line M.5 which, as previously reported, could be induced to express class II antigens with interferon (IFN)-gamma, but failed to stimulate a primary mixed leukocyte reaction. We now show that M.5 cells acquired alloantigen-presenting function, under conditions in which their replication was arrested by X-irradiation, during a 4-day period of exposure to UV-inactivated reovirus, or to IFN-gamma, for induction of class II antigens. The allostimulatory function by M.5 cells could not be explained on the basis of enhanced class II antigen expression, as equivalent numbers of M.5 cells, irradiated after the 4-day exposure to reovirus, or to IFN-gamma, expressed higher amounts of class II antigens, but did not stimulate a primary mixed leukocyte reaction. Early X-irradiation appeared to induce in the class II-expressing M.5 cells a co-stimulatory signal needed for T cell proliferation, similar to that otherwise provided by phorbol esters in this system. Preservation of alloantigen-presenting function by M.5 cells following fixation indicated that this co-stimulatory activity did not reside in a soluble molecule. We surmise that M.5 epithelial cells must provide a least two signals in order to be able to stimulate lymphocyte populations. Consequently, the mode and conditions of epithelial cell activation may determine whether these cells acquire the capacity to serve as antigen-presenting cells, and ultimately whether or not they are able to induce autoimmune disease.
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