All extracted data are stored in a Microsoft Excel spreadsheet. Study selection and data collection process Two reviewers (HK/OMP) independently examine titles and abstracts of all retrieved articles after removing duplicates and select eligible studies. databases such as Medline, EMBASE, Science Citation Index Expanded and Google Scholar from each SKI-II inception through 1 February 2018 and extract data independently. A risk of bias in individual studies is assessed by the Quality in Prognostic Studies tool. Meta-analysis is sought to be conducted if three or more studies report an outcome for a specific autoantibody with the same statistics. If it is inappropriate to combine data due to substantial heterogeneity, the result is reported qualitatively. Subgroup and sensitivity analyses are considered to identify the source of heterogeneity. The Grades of Recommendation, Assessment, Development and Evaluation method is applied to evaluate the evidence level of the result. Ethics and dissemination There is no concerning ethical issue. The result will be sought for publication. PROSPERO registration number CRD42017077336. strong class=”kwd-title” Keywords: idiopathic pulmonary fibrosis, autoantibodies, prognosis, review Strengths and limitations of this study The first systematic review addressing the significance of autoantibodies for idiopathic pulmonary SKI-II fibrosis. The review based on all types of primary studies derived from comprehensive literature search. A potential difficulty in combining the result due to a small number of studies and substantial heterogeneity. Introduction Rationale Interstitial lung disease (ILD) is a heterogeneous clinical entity characterised by common pathological findings of interstitial fibrosis and inflammation.1 It is well recognised that ILD can be accompanied by a variety of connective tissue diseases (CTDs) and caused by certain drug or environmental exposure to some substances.2 3 Accordingly, idiopathic interstitial pneumonia (IIP) can be diagnosed based on the exclusion of these known causes.4 Idiopathic pulmonary fibrosis (IPF) is chronic fibrosing interstitial pneumonia and the most common type among IIPs.1 As IPF is noted to follow a progressive and unfavourable clinical course,5 it is important to make a correct diagnosis of IPF to decide a therapeutic plan and provide proper treatment. However, it is often difficult to detect or exclude underlying CTDs in the diagnosis of IIPs because interstitial pneumonia can be the sole presenting manifestation of certain CTD6 or symptoms or signs of CTD are too subtle to be recognised as the underlying cause.7 Possible involvement of autoimmunity in the development of interstitial pneumonia can be suspected by diverse clinical information such as demographics, physical exams, laboratory tests, radiology and pathological manifestations.8 Nevertheless, some patients remain unclassified into a defined CTD under the current diagnostic criteria. These cases were termed as undifferentiated CTD (UCTD)9 Npy and ILD associated with UCTD has been described by different terminologies, including recently proposed interstitial pneumonia with autoimmune features (IPAF).10 The classification criteria of this disease group consist of a combination of clinical, serological and morphological domains. Some research group reported that patients meeting these criteria demonstrated a different clinical course from SKI-II CTD-ILD or IPF and thus it might be a distinct disease entity.11 However, the sole positivity of autoantibodies without any other symptoms or signs suggestive of CTDs fails to fit into the diagnostic criteria of a defined CTD as well as IPAF.10 According to the current international guideline, IPF with autoantibodies in the absence of additional clinical findings is diagnosed as IPF,5 which, however, seems to be lacking a sufficient explanation. Although some previous studies described that there was no significant difference of mortality between IPF with and without autoantibodies, they are mostly anecdotal SKI-II reports due to a small number of participants in a single institution12 and the significance of autoantibodies in patients with IPF is still uncertain. Therefore, we decided to undertake a systematic review of the literature to summarise previous evidence regarding this clinical question and clarify the prognostic significance of autoantibodies accompanied by IPF. As this article aims to report the rationale and the methodology of a future systematic review.