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Antibodies in Systemic Scleroderma

Author: Shelley Ensz. Scleroderma is highly variable. See Types of Scleroderma. Read Disclaimer
DNA, Topoisomerase I
ANCA and Anti-PR3
ESR (Sed Rate)
PmScl and dsDNA
TNF and IL-13

Overview of Antibodies in Systemic Scleroderma

Abstract by Janet Paulmenn, ISN ArtistDozens of antibodies can occur in systemic scleroderma patients. They can be useful for diagnosing, categorizing and predicting the likelihood of certain complications.

However, scleroderma is always a clinical diagnosis, which means that it is based upon symptoms and not bloodwork. This is because some people with scleroderma never develop antibodies, and also because entirely healthy people can have antibodies but never develop scleroderma or any other autoimmune disease. (Also see: Overview of Antibodies, What is Scleroderma?, Types of Scleroderma and Systemic Symptoms)

Examination of autoantibody status and clinical features that associate with cancer risk and cancer-associated scleroderma. Increased age at scleroderma onset is strongly associated with cancer risk overall. PubMed, Arthritis Rheumatol, 01/20/2015. (Also see: Cancer and Scleroderma)
Early systemic sclerosis (SSc): Analysis of the disease course in patients with marker autoantibody or capillaroscopic positivity or both. The data demonstrate faster progression of SSc in autoantibody–positive patients, particularly in those with preclinical internal organ involvement at baseline, than in autoantibody–negative patients. PubMed, Arthritis Care Res (Hoboken), 2014 Feb 10. (Also see: Capillaroscopy)
What autoantibody tests should become widely available to help scleroderma diagnosis and management? The newly established method for measuring autoantibodies should be carefully evaluated using large international cohorts of SSc patients and other autoimmune conditions, to establish its utility and clinical significance. Arthritis Research and Therapy 2013, 15:116
Systemic sclerosis without antinuclear antibodies (ANA) or Raynaud's phenomenon (RP): a multicentre study in the prospective EULAR Scleroderma Trials and Research (EUSTAR) database. Prospective studies are needed to elucidate the clinical presentation, evolution and outcome of such patients. PubMed, Rheumatology, 2013 Mar;52(3):560-7. (Also see: What is Scleroderma? and Raynaud's)
Autoantibodies in systemic sclerosis. With the advent of array technologies, there is now an unprecedented capability to detect multiple autoantibodies in an individual serum and this long held tenet of clinical diagnostic immunology is being reexamined. Autoimmun Rev, 2012 Jun 25.

Antinuclear Antibodies (ANA)

Definition of Antinuclear antibody. Antinuclear antibodies (ANAs) are found in patients whose immune system is predisposed to cause inflammation against their own body tissues. MedicineNet.com
Antinuclear antibody negative systemic sclerosis. SSc patients who are ANA negative constitute a distinct subset of SSc with less vasculopathy, a greater proportion of males and possibly, more frequent lower gastrointestinal involvement. Seminars in Arthritis and Rheumatism, 11/28/2014.

ANoA: Antinucleolar Antibodies

A new immunoprecipitation-real time quantitative PCR assay for anti-Th/To and anti-U3RNP antibody detection in systemic sclerosis. Our new method readily detects these two clinically important antibodies in SSc. Making tests for anti-Th/To and -U3RNP antibodies widely available to clinicians should be helpful in the diagnosis and follow-up of SSc patients. Arthritis Research and Therapy, 2012.

ACA: Anticentromere Antibodies

Impact of anti-centromere antibodies (ACA) on pulmonary function test (PFT) results in patients with systemic sclerosis without established or suspected pulmonary disease. Patients with ACA, without established or suspected pulmonary complications, have PFT abnormalities consistent with indolent increased pulmonary vascular resistance despite the majority of such patients not subsequently developing PAH. PubMed, Clin Rheumatol, 2014 Apr 22. (Also see: Pulmonary Hypertension Diagnosis)
Centromere Antibody, IgG. Centromere antibody is present in 80-90% of individuals with CREST variant scleroderma. This antibody is also seen in 30% of Raynaud patients, 12% of patients with mixed connective-tissue disease, diffuse scleroderma, interstitial pulmonary fibrosis, primary biliary cirrhosis, and in a smaller percent of patients with systemic lupus erythematosus (SLE) and RA. ARUP Laboratories.

AT1R and ETAR Antibodies

Angiotensin receptor type 1 (AT1R) and endothelin receptor type A (ETAR) on immune cells mediate migration and the expression of IL-8 and CCL18 when stimulated by autoantibodies from systemic sclerosis (SSc) patients. PubMed, Arthritis Res Ther, 2014 Mar 11;16(2):R65. (Also see: Causes of Scleroderma: Endothelin)
Autoantibodies to angiotensin (AT1R) and endothelin (ETAR) receptors in systemic sclerosis (SSc) induce cellular and systemic events associated with disease pathogenesis. Anti-AT1R and anti-ETAR autoantibodies could provide novel targets for therapeutic intervention in the treatment of SSc. PubMed, Arthritis Res Ther, 2014 Jan 28;16(1):R29.

CCP: Anti-Cyclic Citrullinated Peptide Antibodies

Use of antibodies recognizing cyclic citrullinated peptide in the differential diagnosis of joint involvement in systemic sclerosis. Anti-CCP antibodies can be detected in patients with SSc, but less commonly present than in adults with rheumatoid arthritis. PubMed, Clin Rheumatol. 2006 May 3. (Also see: Skeletal Involvement and Rheumatoid Arthritis)

DNA: Anti-DNA and Anti-Topoisomerase I Antibodies

Clinical differences between Thai systemic sclerosis (SSc) patients with positive versus negative anti-topoisomerase l (ATA). A high prevalence of ATA positivity was found among Thai SSc patients and this was associated with a high frequency of hand deformity, anti-centromere negativity, a short duration of pulmonary fibrosis in Diffuse SSc and a lower frequency of Raynaud's phenomenon in Limited SSc. PubMed, Int J Rheum Dis, 10/08/2014.

AECA: Agonistic anti-ICAM-1 Antibodies

Agonistic anti-ICAM-1 antibodies in scleroderma (SSc): Activation of endothelial pro-inflammatory cascades. Anti-endothelial cell antibodies (AECA) from SSc patients target specific endothelial antigens including ICAM-1, and cause pro-inflammatory activation of human endothelial cells, suggesting that they are not only a marker of disease but that they contribute to its progression. PubMed, Vascul Pharmacol, 2013 May 16.S1537-1891(13)00071-2. (Also see: Causes of Scleroderma: Endothelin)

AFA: Antifibroblast Antibodies

Identification of Target Antigens of Antifibroblast Antibodies(AFAs) in Pulmonary Arterial Hypertension (PAH). AFAs detected in patients with PAH recognize cellular targets playing key roles in cell biology and maintenance of homeostasis. B. Terrier. American Journal of Respiratory and Critical Care Medicine Vol 177. pp. 1128-1134, (2008). (Also see: PAH)

ANCA and Anti-PR3

Antineutrophil Cytoplasmic Antibody (ANCA) -Positive Crescentic Glomerulonephritis in Scleroderma (SSc) - A Different Kind of Renal Crisis. The presence of (ANCA and anti-MPO defines a subset of patients with SSc who are susceptible to crescentic glomerulonephritis. These patients may present in a manner identical to scleroderma renal crisis, yet treatment requirements differ significantly. PubMed, J Rheumatol. 2006 Jul 1. (Also see: Renal Involvement)

APA: Antiphospholipid Antibodies

Neurological manifestations of antiphospholipid syndrome. This review summarizes the latest data regarding the clinical aspects, radiological and therapeutic of major neurologic manifestations associated with antiphospholipid antibodies. Rodrigues CE. (PubMed) Eur J Clin Invest, 2010 Apr;40(4):350-9. Epub 2010 Feb 19.

BPI Antibodies

BPI Antibodies: Bactericidal/Permeability-Increasing Protein and Cathepsin G Are the Major Antigenic Targets of Antineutrophil Cytoplasmic Autoantibodies in Systemic Sclerosis. The study included 33 patients with diffuse and 35 with limited SSc. Patients with antibodies to BPI (bactericidal/permeability-increasing protein) had lower skin scores. J Rheumatol NO. 6 JUNE 2003;30:1248-52.

Caspase-3 Antibody

Autoantibody (Ab) against caspase-3, an executioner of apoptosis, in patients with systemic sclerosis (SSc). These results suggest that autoantibody against caspase-3 is generated in SSc and that this Ab is related to the severity of pulmonary fibrosis, vascular damage, and inflammation. Shihoko Okazaki (SpringerLink) Rheumatology International. July 28, 2009.

CRP: C-Reactive Protein

Being Bullied Is Bad for Your Health. Being bullied raises the blood's level of C-Reactive Protein or CRP a marker of systemic inflammation and a risk factor for cardiovascular and other diseases. New York Times, 05/12/2014. (Also see: CRP: C-Reactive Protein)


Eosinophilia in rheumatologic diseases: a prospective study of 1000 cases. Eosinophilia can be seen in various rheumatologic conditions but, as corticosteroids are one of the most common medications used in collagen tissue diseases, the eosinophil numbers found may be lower than expected and eosinophilia may be more frequent than reported. PubMed, Rheumatol Int. 2004 Apr 6.

IgA Antibodies

Reversible IgA deficiency after severe Gram-negative bacteria infection in a patient with systemic sclerosis. Although the mechanism of secondary IgAD is still vague, its association with autoimmune diseases including SSc and also with bacterial infection is discussed. (Springerlink) Masato Yagita. Modern Rheumatology, 27 September 2010. (Also see: Bacterial Infections)

IgG Antibodies

Immunoglobulins. Antibodies attach to the foreign substances so the immune system can destroy them.IgG antibodies are found in all body fluids. They are the smallest but most common antibody (75% to 80%) of all the antibodies in the body. WebMD.
High IgG Signals Autoimmunity in Kids. High levels of immunoglobulin G (IgG) in children — and particularly girls — were associated with the development of autoimmune disease. Med Page Today, 11/11/2013.


Immunodeficiency disorders. Immunodeficiency disorders occur when the body's immune response is reduced or absent. When the immune system detects an antigen, it responds by producing proteins called antibodies that destroy the harmful substances. MedlinePlus.

KU: Anti-KU Antibodies

Anti-Ku antibodies: Clinical, genetic and diagnostic insights. Anti-Ku antibodies are reported in various connective tissue diseases and the Ku complex can be responsible for a very strong autoimmune answer in autoimmune disease. It is postulated that these antibodies could be found in 55% overlap polymyositis/systemic sclerosis patients. Belizna C. (PubMed) Autoimmun Rev, 2010 Jun 4. (Also see: Polymyositis)

LPL: Anti-lipoprotein Lipase Antibody

Anti-lipoprotein lipase antibody in systemic sclerosis: association with elevated serum triglyceride concentrations. The presence of IgG anti-LPL antibody was associated with elevated serum triglyceride levels, greater extent of skin fibrosis, and more frequent presence of lung fibrosis, heart involvement, and anti-topoisomerase I antibodies. J Rheumatol. 2005 Apr;32(4):629-36. (Also see: Skin Fibrosis, Pulmonary Fibrosis, and Cardiac Involvement)


Pathogenic autoantibodies: Emerging insights into tissue injury. Accumulating evidence is emerging that B lymphocytes and autoantibodies are critical in the development of autoimmune disease. Studies of autoantibodies penetrating living cells suggest a dosage effect in generating a biological outcome in vivo. PubMed, 02-28-06. (Also see: Causes of Scleroderma: B and T Cells)

MMP-3 Antibodies

Autoantibody against matrix metalloproteinase-3 in patients with systemic sclerosis. These results suggest that anti-MMP-3 antibody is a serological marker that reflects the severity of SSc and also suggest that it may contribute to the development of fibrosis by inhibiting MMP-3 activity and reducing the ECM (extracellular matrix) turnover. PubMed, Clin Exp Immunol. 2004 Nov;138(2):357-63. (Also see: Skin Fibrosis)

Nucleolar Antibodies

Pulmonary Arterial Hypertension (PAH) and Severe Pulmonary Fibrosis in Systemic Sclerosis Patients with a Nucleolar Antibody. Scleroderma-specific autoantibodies and the FVC%/DLCO% ratio are helpful in determining whether a patient has PAH alone, PAH along with pulmonary fibrosis, or secondary PAH from chronic hypoxia with severe pulmonary fibrosis. J Rheumatol 2007;34:2230-5. (Also see: Pulmonary Hypertension, Pulmonary Fibrosis)

PM/Scl: Anti-PM/SCL-100

Anti-PM/Scl-100 and anti-RNA-polymerase III antibodies in scleroderma (SSc). At high levels, anti-PM/Scl-100 antibodies were associated with SSc, polymyositis, and dermatomyositis, L Maes. (PubMed) Clin Chim Acta, 2010 Jul 4;411(13-14):965-71. (Also See: Antibodies in Scleroderma)

PmScl and dsDNA

Good outcome of interstitial lung disease in patients with scleroderma associated to anti-PM/Scl antibody. Several features and prognosis of ILD in SSc may be modified depending on the identified immunological profile. Seminars in Arthritis and Rheumatism, 07/15/2014. (Also see: Pulmonary Fibrosis Prognosis)


The human exosome and disease. The highest frequency of autoantibodies to components of the exosome complex is found in polymyositis-scleroderma (PM/Scl) overlap patients and therefore the exosome is termed PM/Scl autoantigen in the autoimmune field. Stalls RH. Adv Exp Med Biol, 2011;702:132-42. (Also see: Polymositis).

RNA-Polymerases Antibodies

Malignancies in Italian Patients with Systemic Sclerosis (SSc) Positive for Anti-RNA Polymerase III Antibodies. In a cohort of Italian patients with SSc we observed a significant association between malignancies synchronous to SSc onset and positivity for anti-RNAP III antibodies, similar to that described in American patients with SSc. Paolo Airo. The Journal of Rheumatology jrheum.101144. (Also see: Cancer and Scleroderma)
Researchers Point to Possible Scleroderma-Cancer Link. Those with antibodies called anti-RNA polymerase I/III had the most closely related onset of cancer and scleroderma. EurekAlert! 06/08/10. (Also see: Scleroderma and Cancer)
Association of RNA Polymerase III Antibodies with Scleroderma Renal Crisis (SRC). The authors report that the majority of the SRC patients had anti-topoisomerase I (anti-topo I) antibody (30/46, 65%), whereas a minority of patients (7/46, 15%) had anti-RNA polymerase III (RNAP). Binh Nguyen, MD. Journal of Rheumatology. Vol. 27. No. 5. May 2010. (Also see: Renal Involvement)

RNP Antibodies

Demographic and clinical features of systemic sclerosis (SSc) patients with anti-RNA polymerase III antibodies (RNAP). Measurement of RNAP in SSc patients is useful for the diagnosis and risk stratification of severe manifestation, such as renal crisis and severe skin sclerosis. PubMed, J Dermatol, 12/06/2014.

SCL-70 Antibodies

Fever of unknown origin secondary to type I crescentic glomerulonephritis (CGN) and anti-SCl 70 antibodies without clinical manifestations of systemic sclerosis. Anti-Scl 70 antibodies are highly specific for scleroderma and are seldom present in other diseases. As far as we are aware there are no published cases of the association of type 1 CGN with anti-Scl 70 antibodies. Vega Stieb J. (PubMed) Clin Exp Nephrol. 2008 Oct;12(5):388-92. (Also see: Renal Involvement)
Clinical risk assessment of organ manifestations in systemic sclerosis. Diffuse cutaneous (dcSSc) and a limited cutaneous (lcSSc) subsets are associated with particular organ manifestations, but in this analysis the clinical distinction appeared superseded by an antibody based classification in predicting some scleroderma complications. PubMed, Ann Rheum Dis. 2007 Feb 1. (Also see: Types of Scleroderma)

TAA: Tumor-associated antigens

Tumor-associated antigens (TAAs) in systemic sclerosis and systemic lupus erythematosus: Associations with organ manifestations, immunolaboratory markers and disease activity indices. The production of some TAAs may also be increased in patients with systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and other connective tissue diseases. E Szekanecz. PubMed, Journal of Autoimmunity Vol 31, Issue 4, Dec 2008, Pp 372-376.

TNF and IL-13: Tumor Necrosis Factor and Interleukin-13

Elevated serum levels of a proliferation-inducing ligand in patients with systemic sclerosis: Possible association with myositis? Our preliminary results suggest increased serum a proliferation-inducing ligand (APRIL) levels in systemic sclerosis patients, particularly in those associated with myositis and hypergammaglobinemia. IS Bassyouni. Joint Bone Spine, 2010 Jul 2. (Also see: Tumor Necrosis Factor)
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