Systemic sclerosis, also termed scleroderma, is a multisystem connective tissue disease involving autoimmunity, inflammation, fibrosis and vasculopathy. The clinical presentation of systemic sclerosis is variable in patients and characterized by skin thickening, Raynaud’s phenomenon, vasculopathy-induced tissue death and fibrosis of internal organs.
Panel test:
• Autoantibodies:
o ANA: It’s especially essential for screening of patients that may have some form of scleroderma.
o Scl-70: anti-topoisomerase 1, Autoantibodies against topoisomerase I (anti-Scl 70 antibodies) are the serologic marker of diffuse cutaneous systemic sclerosis
o Anti-RNA Polymerase III Ab: RNA polymerase III antibodies target RNAP III epitopes 11 and 155. Antibodies to three major components of U1-snRNP (snRNP RNP A, U1-snRNP RNP C, U1-snRNP RNP-70kd): U1- are related to scleroderma and inflammatory myopathy overlap syndromes.
o CENP-A, B and C (anti-centromere antibodies): These antibodies are positive in most of CREST patients (The CREST syndrome: calcinosis, Raynaud’s, oesophageal dysmotility, sclerodactyly, and telangiectasia).
o Anti-U3 RNP (Fibrillarin), Anti-fibrillarin (anti-U3RNP) antibodies are related to diffuse cutaneous SSc, numerous visceral involvement, and particularly renal and cardiac involvement. In some patients, anti-fibrillarin antibodies are associated to severe pulmonary disease, pulmonary hypertension, severe small bowel involvement, and a poor prognosis.
o Th/To: Anti-Th/To antibodies predominantly attach to 2 proteins of the mitochondrial RNA processing (MRP) and also the ribonuclease P complexes, are present in 1-13% of SSc patients, and are rarely detected in other diseases. Anti-Th/To antibodies are primarily associated with localized cutaneous scleroderma, and associated with pericarditis, interstitial lung disease and a high frequency of “intrinsic pulmonary hypertension, and a poorer prognosis.
o PM/Scl-100 and PM/Scl-75: Autoantibodies to PM/Scl, the human exosome complex, are detected in polymyositis/scleroderma overlap syndromes. The majority of anti-PM/Scl reactivity is directed to one of two proteins: PM/Scl100 and/or PM-Scl75.
Other tests
• Immunoglobulins – hypergammaglobulinemia
• Rheumatoid factor, anti-citrullinated antibodies – often positive
References:
1. Knobler R, Moinzadeh P, Hunzelmann N, Kreuter A, Cozzio A, Mouthon L, Cutolo M, Rongioletti F, Denton CP, Rudnicka L, Frasin LA, Smith V, Gabrielli A, Aberer E, Bagot M, Bali G, Bouaziz J, Olesen B, Foeldvari I, Frances C, Jalili A, Just U, Kähäri V, Kárpáti S, Kofoed K, Krasowska D, Olszewska M, Orteu C, Panelius J, Parodi A, Petit A, Quaglino P, Ranki A, Schmidt JM, Seneschal J, Skrok A, Sticherling M, Sunderkötter C, Taieb A, Tanew A, Wolf P, Worm M, Wutte NJ, Krieg T. European Dermatology Forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes. J Eur Acad Dermatol Venereol. 2017; 31(9): 1401-1424. PubMed
2. Tartar DM, Chung L, Fiorentino DF. Clinical significance of autoantibodies in dermatomyositis and systemic sclerosis. Clin Dermatol. 2018; 36(4): 508-524. PubMed
