Systemic Autoimmune Disease

Idiopathic Inflammatory Myopathy

Idiopathic inflammatory myopathies (IIM’s) are a heterogeneous group of muscle diseases. It is generally believed that the autoimmune response to antigens derived from their own tissues is responsible for the muscle fiber damage and muscle weakness. The IIM’s are classified on the basis of patterns of presentation, age at onset, and immunohistopathologic features in skin and muscle biopsy specimens.

Polymyositis (PM) and dermatomyositis (DM) are two of the main classes of idiopathic inflammatory myopathy. Moreover, the lung is the most common extracellular organ involved in PM/DM. Pulmonary complications, such as interstitial lung disease (ILD), occur in a high percentage of patients resulting in significant morbidity and mortality. Patients with PM/DM also often develop malignancies over the course of the disease including lung, breast, ovarian and colon cancer, as well as an association with higher mortality rates.

There are a number of myositis-specific autoantibodies (Figure 1) associated with PM/DM and which are connected with the clinical manifestations of the disease (Table 1).

Table 1.

MSAsClinical features
ARS
Muscle and skin symptoms / Interstitial lung disease (ILD)
MDA5
Clinically amyopathic DM (CADM) / Rapidly progressive interstitial lung disease (RP-ILD)
TIF1-γ
Cancer associated myositis (CAM)
Mi-2
Milder muscle disease / Better response to treatments
SRP
Severe myositis with relatively acute onset / Resistance to treatments

Anti-aminoacyl tRNA synthetase (Anti-ARS) antibody

Anti-aminoacyl tRNA synthetase (ARS) antibodies have been found to be highly specific for PM/DM and to correlate with the pulmonary complication of interstitial lung disease (ILD).1

ILD is a heterogeneous syndrome with several common clinical features, such as exertional dyspnea, bilateral diffuse infiltrates, abnormal respiratory physiology, absence of pulmonary infection and neoplasm, and fibrosis in the pulmonary parenchyma. Collagen tissues disease (CTD)-associated ILD is a type of ILD and may be a major cause of morbidity and mortality in CTD including PM/DM.2

Some cases of ILD with anti-ARS antibodies can have no symptoms of myositis. A retrospective study reported that patients with anti-ARS antibody-positive ILD have common pulmonary manifestations regardless of the presence of PM/DM.3 It suggest that anti-ARS antibodies can be detected in patients with idiopathic (‘‘unexplained’’) ILD, which would require consultations with a pulmonologist.

In addition, although surgical pulmonary biopsy is quite helpful in performing the differential diagnosis between several type of idiopathic ILD,4 it can be invasive. If some patients who have no extrapulmonary manifestations are positive with anti-ARS antibodies, they can have an appropriate diagnosis and treatment without lung biopsy.

A recent study reported that 30.8% (77/250) of IIM patients were positive with anti-ARS antibodies, and only 13.8% (34) were anti-Jo-1 positive.5 The study also indicated that 10.8% (18/168) of idiopathic ILD patients were anti-ARS positive. This was triple the number of anti-Jo-1 positive idiopathic ILD patient.

The MESACUP Anti-ARS TEST (Anti-Synthetase  ELISA Kit Code# RG-7841EC-D, for sale in EU only) can detect human antibodies against five recombinant proteins (Jo-1, PL-7, PL-12, EJ, and KS) in single well assay with over 99.5% consistency with “gold standard” RNA precipitation method. This assay will enable easier and wider use in the detection of anti-ARS antibodies in patients with IIM and idiopathic ILD.

 

Systemic sclerosis (SSc)

Systemic sclerosis (SSc) or systemic scleroderma is a chronic multisystem connective tissue disease that affects the skin and internal organs, such as heart, lung, gastrointestinal tracts, and kidneys. The prevalence of SSc varies worldwide, and recent studies reported to be 88 to 443 cases per 1,000,000 people.6 The disease is most frequently found in 30-50 year-old women. SSc can be subcategorized into several subsets.

Table 2.

SSc SubsetsClinical features
Limited SSc
Skin manifestations are restricted to the hands, the distal forearms
Formerly identified as CREST* syndrome
Association with autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC)
Diffused SSc
Skin manifestations also are proximal extremities and trunk of the body
Worse prognosis and faster disease progression than limited SSc
Association with renal crisis (rapidly progressive renal failure)
SSc without skin involvement Internal organs involvement only
Overlap syndrome
Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or inflammatory myopathy is complicated with SSc

Antinuclear antibodies (ANAs) are present in sera of nearly all patients with SSc. The three major characteristic autoantibodies on SSc are targeting to topoisomerase I (Scl-70), centromere proteins like CENP-B, and RNA polymerase III. The detection of these antibodies are strongly supportive for diagnosis of SSc and prediction of its subsets. In 2013, these SSc-related autoantibodies have been incorporated to new classification criteria for SSc.7

  1. Matsushita T, et al. 34: 1012-1018, 2007 [PubMed: 17309126]
  2. Cottin V. Eur. Respir. Rev. 22: 26-32, 2013 [PubMed: 23457161]
  3. Takato H, et al. Respir. Med. 107: 128-133, 2013 [PubMed: 23137883]
  4. Raghu G, et al. Respir. Crit. Care Med. 183: 788-824, 2011 [PubMed: 21471066]
  5. Nakashima R, et al. PLoS One. 9: e85062, 2014 [PubMed: 24454792]
  6. Barnes J, et al. Curr. Opin. Rheumatol. 24: 165-170, 2014 [PubMed: 22269658]
  7. van den Hoogen F, et al. Ann. Rheum. Dis. 72: 1747-1755, 2013 [PubMed: 24092682]
  8. Kuwana M, et al. Arthritis Rheum. 37: 75-83, 1994 [PubMed: 8129766]
  9. Satoh T, et al. Rheumatology. 48: 1570-1574, 2009 [PubMed: 19808694]
  10. Moinzadeh P, et al. Arthritis. Res. Ther. 16: R53, 2014 [PubMed: 24524733]
  11. Airo‘ P, et al. J. Rheumatol. 38: 1329-1334, 2011 [PubMed: 21459934]

*CREST syndrome: Calcinosis, Raynaud’S phenomenon, Esophageal dismotility, Sclerodactyly, and Telangiectasias