Pulmonology Quicklinks
Autoimmune Diseases
Autoimmune diseases (also known as connective tissue diseases or rheumatologic diseases) are systemic inflammatory disorders that exhibit autoimmune-mediated damage due to circulating autoantibodies that target various body organs and cause immune-mediated tissue damage. Lungs are a frequent target, and pulmonary manifestations may be the presenting feature or develop after the diagnosis of autoimmune diseas-es. One potential manifestation that many autoimmune disorders have in common is ILDs.1-3
All patients with an autoimmune condition are at risk of developing ILDs, and those with antisynthetase syndrome, systemic sclerosis, polymyo-sitis/dermatomyositis, and rheumatoid arthritis bear particularly higher risks of developing ILDs.1-4
Prevalence of ILD among Autoimmune Diseases3-10
Serology
The pathophysiology of autoimmune diseases includes a malfunctional immune system, where lymphocytes that recognize autoantigens do not undergo programmed cell death nor become non-functional, producing autoantibodies against human antigens.11 As autoantibodies are overexpressed in autoimmune conditions, they can be detected in rheumatic disorders to aid the diagnostic process. As healthy individuals and patients with non-autoimmune diseases can still have autoantibodies, the use of serologic tests should only be used to support a diagnosis along with appropriate signs and symptoms and comprehensive clinical evaluation.12 For example, the American College of Rheumatology does not recommend ordering specific sub-serologic tests without a positive ANA and clinical suspicion for an autoimmune disease.13 Additionally, some autoantibodies are found to be highly specific to one disease, for example, autoantibodies against aminoacyl-tRNA synthetases (anti-ARS) for polymyositis and dermatomyositis or anti-SS-A for Sjögren’s syndrome, while others are not so.12,13 The chart below summarizes few serologic markers that are commonly detected in different autoimmune disorders.14
| Antisynthetase syndrome | Anti-ARS, anti-Jo1 |
| Systemic sclerosis (SSc) | Anti-Scl-70, anti-U3-RNP (also called antifibrillarin), anti-Th/To [ribonucleoproteins] |
| Polymyositis/Dermatomyositis (PM/DM) | Anti-ARS, anti-SRP (signal recognition particle), anti-Mi-2, anti-p155/140, anti-SAE (small ubiquitin-like modifier activating enzyme), anti-CADM-140 (also called MDA5) |
| Mixed connective tissue disease | Anti-U1-RNP, ANA, RF |
| Sjögren’s syndrome | ANA, anti-Ro/SS-A, anti-La/SS-B, RF |
| Rheumatoid arthritis | RF, anti-CCP/ACPA |
| Systemic lupus erythematosus (SLE) | ANA, anti-dsDNA, anti-Sm |
Rheumatoid factors (RFs): immunoglobulins against the Fc region of IgG.12
Antibodies to cyclic citrullinated peptides (anti-CCP): antibodies to proteins in epithelial cell differentiation; also called anti-citrullinated peptide antibodies (ACPA).12
Antinuclear antibodies (ANA): immunoglobulins that bind to antigen in the cell nucleus.12
Antibodies to DNA (anti-dsDNA): antibodies against extracellular DNA after apoptosis.12
Antibodies to extractable nuclear antigens (ENAs): antibodies against proteins in the cell nucleus. They are named ‘extractable’ because these proteins can be removed from the cell nucleus. The six main protein types are Ro (also known as SS-A), La (also known as SS-B), Sm, ribonuclear protein (RNP), topoisomerase I (also known as Scl-70), and Jo1. Autoantibodies to these antigens are typically associated with a particular underlying autoimmune disorder.12
Antiphospholipid antibodies: antibodies that bind to phospholipids such as cardiolipin.12
HRCT
Patterns of autoimmune ILDs on HRCT are not apparent, as one disease may have different patterns in different patients. The patterns may also co-exist or change in the same patient. However, there is a common pattern that can assist diagnosis of autoimmune ILDs, with NSIP being the most common HRCT pattern seen in most patients with autoimmune ILDs.14
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Evaluation, Diagnosis and Management of Systemic Sclerosis—Associated Interstitial Lung Disease: A Multidisciplinary Roundtable Discussion
REFERENCES
- Mathai SC, Danoff SK. Management of interstitial lung disease associated with connective tissue disease. BMJ. 2016;352:h6819. Published 2016 Feb 24. doi:10.1136/bmj.h6819.
- Solomon JJ, Fischer A. Connective Tissue Disease-Associated Interstitial Lung Disease: A Focused Review. J Intensive Care Med. 2015;30(7):392-400. doi:10.1177/0885066613516579.
- Castelino FV, Varga J. Interstitial lung disease in connective tissue diseases: evolving concepts of pathogenesis and management. Arthritis Res Ther. 2010;12(4):213. doi:10.1186/ar3097.
- Witt LJ, Curran JJ, Strek ME. The Diagnosis and Treatment of Antisynthetase Syndrome. Clin Pulm Med. 2016;23(5):218-226. doi:10.1097/CPM.0000000000000171.
- Flament T, Bigot A, Chaigne B, Henique H, Diot E, Marchand-Adam S. Pulmonary manifestations of Sjögren's syndrome. Eur Respir Rev. 2016;25(140):110-123. doi:10.1183/16000617.0011-2016.
- Spagnolo P, Cordier JF, Cottin V. Connective tissue diseases, multimorbidity and the ageing lung. Eur Respir J. 2016;47(5):1535-1558. doi:10.1183/13993003.00829-2015.
- Ha YJ, Lee YJ, Kang EH. Lung Involvements in Rheumatic Diseases: Update on the Epidemiology, Pathogenesis, Clinical Features, and Treatment. Biomed Res Int. 2018;2018:6930297. Published 2018 May 8. doi:10.1155/2018/6930297.
- de Lauretis A, Veeraraghavan S, Renzoni E. Review series: Aspects of interstitial lung disease: connective tissue disease-associated interstitial lung disease: how does it differ from IPF? How should the clinical approach differ?. Chron Respir Dis. 2011;8(1):53-82. doi:10.1177/1479972310393758.
- Graney BA, Fischer A. Advocating for early interstitial lung disease detection in mixed connective tissue disease. Rheumatology (Oxford). 2018;57(2):204-205. doi:10.1093/rheumatology/kex256.
- Steele R, Hudson M, Lo E, Baron M; Canadian Scleroderma Research Group. Clinical decision rule to predict the presence of interstitial lung disease in systemic sclerosis. Arthritis Care Res (Hoboken). 2012;64(4):519-524. doi:10.1002/acr.21583.
- Diamond B, Lipsky PE. Chapter 377e: Autoimmunity and Autoimmune Diseases. In: Kasper DL, Fauci A, Hauser S, eds. Harrison’s Principles of Internal Medicine. 19th ed. McGraw-Hill Education; 2015:377e-1-5.
- das Neves MF, Irlapati R, Isenberg D. Chapter 25: Laboratory Tests. In: Adebajo A, Dunkley L, eds. ABC of Rheumatology. 5th ed. John Wiley & Sons, Inc.; 2018:169-176.
- Ali Y. Rheumatologic Tests: A Primer for Family Physicians. Am Fam Physician. 2018;98(3):164-170.
- Jee AS, Adelstein S, Bleasel J, et al. Role of Autoantibodies in the Diagnosis of Connective-Tissue Disease ILD (CTD-ILD) and Interstitial Pneumonia with Autoimmune Features (IPAF). J Clin Med. 2017;6(5):51. Published 2017 May 4. doi:10.3390/jcm6050051.
