Interpretation of autoantibody positivity in interstitial lung disease and lung-dominant connective tissue disease

Pereira, Daniel; Kawassaki, Alexandre de Melo; Baldi, Bruno Guedes

doi:10.1590/s1806-37132013000600012

Cited by 6 publications

(8 citation statements)

References 51 publications

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“…Additionally, these mice models do not replicate all clinical cases, as some patients present with pulmonary disease and/or ACPA positivity prior to onset of articular disease. While the manifestation of lung-dominant CTD is a noted clinical phenomenon, the interpretation of autoantibody screenings in idiopathic lung disease is still under debate [145].…”

Section: Current Theories Of Ra-ild Pathogenesis and Reconciling Nsipmentioning

confidence: 99%

Reinterpreting Evidence of Rheumatoid Arthritis-Associated Interstitial Lung Disease to Understand Etiology

Ambrosini

Kottmann

et al. 2019

CRR

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Interstitial lung disease (ILD) is a well-known complication ofrheumatoid arthritis (RA) which often results in significant morbidity and mortality. It is often diagnosed late in the disease process via descriptive criteria. Multiple subtypes ofRA-ILD exist as defined by chest CT and histopathology [1]. In the absence of formal natural history studies and definitive diagnostics, a conventional dogma has emerged that there are two major subtypes ofRA-ILD (nonspecific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP)). These subtypes are based on clinical experience and correlation studies [2–4]. However, recent animal model data are incongruous with established paradigms ofRA- ILD and beg reassessment of the clinical evidence in order to better understand etiology, pathogenesis, prognosis, and response to therapy. To this end, here we: 1) review the literature on epidemiology, radiology, histopathology and clinical outcomes of the various RA-ILD subtypes, existing animal models, and current theories on RA-ILD pathogenesis; 2) highlight the major gaps in our knowledge; and 3) propose future research to test an emerging theory of RA-ILD that posits initial rheumatic lung inflammation in the form of NSIP-like pathology transforms mesenchymal cells to derive chimeric disease, and subsequently develops into frank UIP-like fibrosis in some RA patients. Elucidation of the pathogenesis ofRA-ILD is critical for the development of effective interventions for RA-ILD.

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Section: Current Theories Of Ra-ild Pathogenesis and Reconciling Nsipmentioning

confidence: 99%

Reinterpreting Evidence of Rheumatoid Arthritis-Associated Interstitial Lung Disease to Understand Etiology

Ambrosini

Kottmann

et al. 2019

CRR

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“…Therefore, the interpretation of positive autoantibody tests can be challenging in diseases such as thyroiditis, as anti-thyroid autoantibodies may precede disease manifestation by two decades, and some individuals (10%) stay disease-free despite the presence of autoantibodies6. Data interpretation is further complicated in diseases with complex pathologies, such as CTD, an autoimmune-inflammatory disease7. Furthermore, autoantibodies may be produced temporarily to facilitate communication between immune cells and molecules or between immune cells and other tissues, particularly during immune challenges such as viral infections8.…”

mentioning

confidence: 99%

Demographic associations for autoantibodies in disease-free individuals of a European population

Haller-Kikkatalo

Alnek

Metspalu

et al. 2017

Sci Rep

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The presence of autoantibodies usually precedes autoimmune disease, but is sometimes considered an incidental finding with no clinical relevance. The prevalence of immune-mediated diseases was studied in a group of individuals from the Estonian Genome Project (n = 51,862), and 6 clinically significant autoantibodies were detected in a subgroup of 994 (auto)immune-mediated disease-free individuals. The overall prevalence of individuals with immune-mediated diseases in the primary cohort was 30.1%. Similarly, 23.6% of the participants in the disease-free subgroup were seropositive for at least one autoantibody. Several phenotypic parameters were associated with autoantibodies. The results suggest that (i) immune-mediated diseases are diagnosed in nearly one-third of a random European population, (ii) 6 common autoantibodies are detectable in almost one-third of individuals without diagnosed autoimmune diseases, (iii) tissue non-specific autoantibodies, especially at high levels, may reflect preclinical disease in symptom-free individuals, and (iv) the incidental positivity of anti-TPO in men with positive familial anamnesis of maternal autoimmune disease deserves further medical attention. These results encourage physicians to evaluate autoantibodies in addition to treating a variety of patient health complaints to detect autoimmune-mediated disease early.

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“…There is growing recognition that ILD might be the first or an isolated manifestation of a CTD. ( 21 ) In 1995, Homma et al, ( 22 ) having followed, for up to 11 years, 68 patients in whom the initial evaluation showed no clinical or serological evidence of CTD, ( 1 ) showed that it is possible for ILD to be the sole presentation of occult CTD. Homma et al ( 22 ) showed that the incidence of definite CTD during long-term follow-up was 19%, similar to the rate observed in the present study, and also found no difference between patients who have definite CTD and LD-CTD patients from a clinical or serological standpoint.…”

Section: Discussionmentioning

confidence: 99%

“…There is a dilemma surrounding the classification of patients with interstitial lung diseases (ILDs) and clinical features that are suggestive of formes frustes (limited forms) of connective tissue disease (CTD), because such patients do not meet the accepted rheumatological criteria for a definitive diagnosis of CTD. ( 1 - 3 ) Since the first recognition of the nonspecific interstitial pneumonia (NSIP) pattern as a possible independent disease, it has been strongly associated with CTD. ( 4 ) Previous studies have shown different characteristics regarding the prognosis and natural history of idiopathic interstitial pneumonia (IIP) with a "rheumatological flavor" but without a definitive diagnosis of CTD.…”

Section: Introductionmentioning

confidence: 99%

Lung-dominant connective tissue disease among patients with interstitial lung disease: prevalence, functional stability, and common extrathoracic features

et al. 2015

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OBJECTIVE: To describe the characteristics of a cohort of patients with lung-dominant connective tissue disease (LD-CTD). METHODS: This was a retrospective study of patients with interstitial lung disease (ILD), positive antinuclear antibody (ANA) results (≥ 1/320), with or without specific autoantibodies, and at least one clinical feature suggestive of connective tissue disease (CTD). RESULTS: Of the 1,998 patients screened, 52 initially met the criteria for a diagnosis of LD-CTD: 37% were male; the mean age at diagnosis was 56 years; and the median follow-up period was 48 months. During follow-up, 8 patients met the criteria for a definitive diagnosis of a CTD. The remaining 44 patients comprised the LD-CTD group, in which the most prevalent extrathoracic features were arthralgia, gastroesophageal reflux disease, and Raynaud's phenomenon. The most prevalent autoantibodies in this group were ANA (89%) and anti-SSA (anti-Ro, 27%). The mean baseline and final FVC was 69.5% and 74.0% of the predicted values, respectively (p > 0.05). Nonspecific interstitial pneumonia and usual interstitial pneumonia patterns were found in 45% and 9% of HRCT scans, respectively; 36% of the scans were unclassifiable. A similar prevalence was noted in histological samples. Diffuse esophageal dilatation was identified in 52% of HRCT scans. Nailfold capillaroscopy was performed in 22 patients; 17 showed a scleroderma pattern. CONCLUSIONS: In our LD-CTD group, there was predominance of females and the patients showed mild spirometric abnormalities at diagnosis, with differing underlying ILD patterns that were mostly unclassifiable on HRCT and by histology. We found functional stability on follow-up. Esophageal dilatation on HRCT and scleroderma pattern on nailfold capillaroscopy were frequent findings and might come to serve as diagnostic criteria.

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Interpretation of autoantibody positivity in interstitial lung disease and lung-dominant connective tissue disease

Cited by 6 publications

References 51 publications

Reinterpreting Evidence of Rheumatoid Arthritis-Associated Interstitial Lung Disease to Understand Etiology

Reinterpreting Evidence of Rheumatoid Arthritis-Associated Interstitial Lung Disease to Understand Etiology

Demographic associations for autoantibodies in disease-free individuals of a European population

Lung-dominant connective tissue disease among patients with interstitial lung disease: prevalence, functional stability, and common extrathoracic features

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