Identification of connective tissue disease autoantibodies and a novel autoantibody anti-annexin A11 in patients with "idiopathic" interstitial lung disease.

BACKGROUND: Autoantibodies are a hallmark feature of Connective Tissue Diseases (CTD). Their presence in patients with idiopathic interstitial lung disease (ILD) may suggest covert CTD. We aimed to determine the prevalence of CTD autoantibodies in patients diagnosed with idiopathic ILD. METHODS: 499 patient sera were analysed: 251 idiopathic pulmonary fibrosis (IPF), 206 idiopathic non-specific interstitial pneumonia (iNSIP) and 42 cryptogenic organising pneumonia (COP). Autoantibody status was determined by immunoprecipitation. RESULTS: 2.4% of IPF sera had a CTD-autoantibody compared to 10.2% of iNSIP and 7.3% of COP. 45% of autoantibodies were anti-synthetases. A novel autoantibody targeting an unknown 56 kDa protein was found in seven IPF patients (2.8%) and two NSIP (1%) patients. This was characterised as anti-annexin A11. CONCLUSION: Specific guidance on autoantibody testing and interpretation in patients with ILD could improve diagnostic accuracy. Further work is required to determine the clinical significance of anti-annexin A11.

Increasing incidence of adult idiopathic inflammatory myopathies in the City of Salford, UK: a 10-year epidemiological study.

OBJECTIVES: The aim was to identify and characterize all incident adult cases of idiopathic inflammatory myopathies (IIM) between 1 January 2007 and 31 December 2016 in the City of Salford, UK. METHODS: Adults first diagnosed with IIM within the study period were identified by: a Salford Royal NHS Foundation Trust (SRFT) inpatient episode IIM-specific ICD-10 coding search; all new patient appointments to SRFT neuromuscular outpatient clinics; and all Salford residents enrolled within the UKMYONET study. All patients with definite IIM by the 2017 EULAR/ACR classification criteria were included, as were probable cases if consensus expert opinion agreed. Cases were excluded if <18 years of age at disease onset, if they did not meet probable criteria or when probable but expert opinion concluded a non-IIM diagnosis. RESULTS: The multimodal case ascertainment identified 1156 cases which, after review and application of exclusion criteria, resulted in 32 incident cases during the study period. Twenty-three of 32 were female, with a mean age of 58.1 years. The mean incidence of adult IIM was 17.6/1 000 000 person years, and higher for females than for males (25.2 vs 10.0/1 000 000 person years, respectively). A significant incidence increase over time was apparent (13.6 vs 21.4/1 000 000 person years; P = 0.032). Using EULAR/ACR classification criteria, the largest IIM subtype (21/32) was PM, followed by DM (8/32), IBM (2/32) and amyopathic DM (1/32). Expert opinion subtype differed from EULAR/ACR classification criteria in 19/32 cases. CONCLUSION: The incidence of adult IIM in Salford is 17.6/1 000 000 person years, higher in females, and is increasing over time. Disagreement exists between EULAR/ACR-derived and expert opinion-derived IIM subtype assignments.

The utility of comprehensive autoantibody testing to differentiate connective tissue disease associated and idiopathic interstitial lung disease subgroup cases.

Interstitial lung disease (ILD) comprises many heterogeneous disease groups, the largest being CTD-associated and those labelled as idiopathic out of necessity. The mechanisms causing ILD are poorly understood, but most CTD- and idiopathic-ILD cases can respond to immunosuppression, clearly suggesting a pathological role for inflammation. By contrast, corticosteroid immunosuppression causes harm without benefit in the feared idiopathic pulmonary fibrosis, suggesting that inflammation plays little pathological role, and where ILD progresses rapidly to lethal outcome even with anti-fibrotic drug use. Given the treatment response differences apparent between ILD subgroups, and the dangers and costs of corticosteroid and anti-fibrotic drug use, respectively, it has become vital in every ILD patient to make an accurate subgroup diagnosis, to optimize treatment selections. This review discusses why differentiating CTD- and idiopathic-ILD subgroup cases remains so problematic, and why existing comprehensive CTD-specific serology would, if generally available, represent an ideal biomarker tool to enhance ILD subgroup diagnostic accuracy.