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Correspondence |

Autoantibodies Are Already Found in Connective Tissue Disease-Associated Interstitial Lung Disease FREE TO VIEW

La-He Jearn, MD; Think-You Kim, MD
Author and Funding Information

FINANCIAL/NONFINANCIAL DISCLOSURES: The authors have reported to CHEST the following: T.-Y. K. holds patents relating to the IT-1 cell line. None declared (L.-H. J.).

Department of Diagnostic Immunology/Lab. Medicine, Hanyang University Medical Center, Seoul, South Korea

CORRESPONDENCE TO: Think-You Kim, MD, Department of Diagnostic Immunology/Lab. Medicine, Hanyang University Medical Center, 222-1 Wangsimni-ro, Seongdong-gu, Seoul, 04763, South Korea


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(3):753-755. doi:10.1016/j.chest.2016.06.036
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Published online

We read with interest the article by Hu and colleagues in a recent issue of CHEST (January 2016). However, we noted several key omissions, which are subsequently discussed.

First, there was no information regarding the detection methods of autoantibodies; this is of interest because sensitivity and specificity can vary according to the selected method.

Second, the antinuclear antibody test, which is a basic test for diagnosing connective tissue disease (CTD), was not included in the follow-up examinations. This seems to be a serious problem and casts doubt on a series of data presented in the report; we wonder whether the conclusion properly reflects the status of the autoantibodies.

Third, anticitrullinated protein antibodies (ACPA) such as anticyclic citrullinated peptide (CCP), antiperinuclear factor (APF), and antikeratin antibody were not tested. ACPA is notable for its recently emerging association with lung pathology.

CTD-interstitial lung disease (ILD) is a subject of great interest to us, because The Hospital for Rheumatic Diseases is a part of our medical center. Therefore, we retrospectively investigated cases of patients with ILD whose autoantibodies were tested at diagnosis. We have performed the autoimmune target test using the IT-1 cell line instead of the antinuclear antibody test using the HEp-2 cell line and reported its excellence in autoantibody testing. We investigated 324 patients with autoimmune target test results among 1,738 patients diagnosed with ILD and analyzed the results of the rheumatoid factor and ACPA (APF or anti-CCP). Our studies were approved by our Institutional Review Board.

Patients with CTD-ILD were mostly (98.1%) seropositive, which is our usual experience (Table 1). Of great interest, autoantibodies were detected in 95.7% of ILDs with autoimmune features and 89.1% of other ILDs.

Table Graphic Jump Location
Table 1 Results of AIT tests, ACPAs, and RFs in Patients With ILD at Diagnosis (n = 324)
a One positive result among the three tests was considered to be seropositive.

Data are presented as No. (%). ACPAs were performed by one or both of two tests that were APF and anti-CCP. AIT and APF tests were performed by an indirect immunofluorescent method (IT-AIT and IT-APF; ImmunoThink). Anti-CCP was detected by second-generation enzyme-linked immunosorbent assay (Axis-Shield and Immco Diagnostics). RF was tested by nephelometry (Dade Behring Marburg and Beckman Coulter). ACPA = anticitrullinated protein antibody; AF = autoimmune features; AIT = autoimmune target; APF = antiperinuclear factor; CCP = cyclic citrullinated peptide; CTD = connective tissue disease; ILD = interstitial lung disease; NT = not tested; RF = rheumatoid factor.

The results showing the overall high positive rates of autoantibodies in patients with ILD regardless of the disease type are very consistent with a recent review, which reported that lungs may be the origin of systemic autoimmunity. This interesting thesis is that lung tissue inflammation caused by genetic, environmental, or microbiome factors may contribute to post-translational modifications, such as citrullination or carbamylation, which could trigger an autoimmune reaction. Based on this, any patient with suspected ILD needs to be checked for autoantibodies. Regretfully, we could not undertake a full analysis because only a small proportion of the patients with ILD (18.6%; 324 of 1,738) were tested at diagnosis.

We believe that autoantibody tests should be used more actively in lung diseases because various autoantibody tests are implicated in the area of hepatic diseases.

References

Hu Y. .Wang L.S. .Wei Y.R. .et al Clinical characteristics of connective tissue disease-associated interstitial lung disease in 1,044 Chinese patients. Chest. 2016;149:201-208 [PubMed]journal. [CrossRef] [PubMed]
 
Jearn L.H. .Kim T.Y. . Level of anticitrullinated peptide/protein antibody is not associated with lung diseases in rheumatoid arthritis. J Rheumatol. 2012;39:1493-1494 [PubMed]journal. [CrossRef] [PubMed]
 
Jearn L.H. .Kim T.Y. . Anti-Jo1 antibody in polymyositis/dermatomyositis is still closely associated with lung rather than joints. J Rheumatol. 2015;42:1060- [PubMed]journal
 
Jearn L.H. .Kim D.A. .Kim T.Y. . Limitations of antinuclear antibody tests (HEp-2) are overcome with the autoimmune target test (IT-1) in systemic lupus erythematosus. J Rheumatol. 2009;36:1833-1834 [PubMed]journal
 
Klareskog L. .Catrina A.I. . Autoimmunity: lungs and citrullination. Nat Rev Rheumatol. 2015;11:261-262 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Tables

Table Graphic Jump Location
Table 1 Results of AIT tests, ACPAs, and RFs in Patients With ILD at Diagnosis (n = 324)
a One positive result among the three tests was considered to be seropositive.

Data are presented as No. (%). ACPAs were performed by one or both of two tests that were APF and anti-CCP. AIT and APF tests were performed by an indirect immunofluorescent method (IT-AIT and IT-APF; ImmunoThink). Anti-CCP was detected by second-generation enzyme-linked immunosorbent assay (Axis-Shield and Immco Diagnostics). RF was tested by nephelometry (Dade Behring Marburg and Beckman Coulter). ACPA = anticitrullinated protein antibody; AF = autoimmune features; AIT = autoimmune target; APF = antiperinuclear factor; CCP = cyclic citrullinated peptide; CTD = connective tissue disease; ILD = interstitial lung disease; NT = not tested; RF = rheumatoid factor.

References

Hu Y. .Wang L.S. .Wei Y.R. .et al Clinical characteristics of connective tissue disease-associated interstitial lung disease in 1,044 Chinese patients. Chest. 2016;149:201-208 [PubMed]journal. [CrossRef] [PubMed]
 
Jearn L.H. .Kim T.Y. . Level of anticitrullinated peptide/protein antibody is not associated with lung diseases in rheumatoid arthritis. J Rheumatol. 2012;39:1493-1494 [PubMed]journal. [CrossRef] [PubMed]
 
Jearn L.H. .Kim T.Y. . Anti-Jo1 antibody in polymyositis/dermatomyositis is still closely associated with lung rather than joints. J Rheumatol. 2015;42:1060- [PubMed]journal
 
Jearn L.H. .Kim D.A. .Kim T.Y. . Limitations of antinuclear antibody tests (HEp-2) are overcome with the autoimmune target test (IT-1) in systemic lupus erythematosus. J Rheumatol. 2009;36:1833-1834 [PubMed]journal
 
Klareskog L. .Catrina A.I. . Autoimmunity: lungs and citrullination. Nat Rev Rheumatol. 2015;11:261-262 [PubMed]journal. [CrossRef] [PubMed]
 
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